Bio


My career has been devoted to understanding the neural mechanisms involved in brain aging and brain plasticity, with a special focus on early detection and prevention of Alzheimer’s disease (AD). My research approach integrates principles and findings from cognitive theory, clinical neuroscience, and computational neuroscience. This approach is complemented by my extensive research experience involving multi-modality neuroimaging (PET, sMRI, dMRI, and fMRI), psychophysiology, neuropsychology, and quantitative research methods. I currently lead an interdisciplinary clinical neuroscience lab, covering a wide spectrum of research from Phases 0-2 in three areas: (a) brain aging, focusing on the links between brain pathophysiology and clinical symptoms, in a wide range of populations, from older adults with superior cognitive capacity to preclinical and prodromal AD, with an overarching aim to gain insights into the broad mechanisms of aging, both in typical and atypical populations and to identify early biomarkers for AD; (b) novel non- pharmacological interventions that promote successful cognitive aging as well as alleviate or eliminate adverse effects of AD pathophysiology; and (c) advanced computational models (e.g., explainable AI) for understanding and intervening on brain aging.

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Member, Nonpharmacological Interventions Committee, Alzheimer’s Clinical Trials Consortium, NIH (2018 - Present)
  • Invited lecturer, NIH CSR (2022 - Present)
  • Standing member, SPIP study panel, NIH (2020 - Present)

Professional Education


  • BA, Jilin University, China (2005)
  • Medical education, Jilin University, China (2006)
  • PhD, University of Wisconsin-Madison (2011)
  • Postdoc, University of Rochester (2013)

Current Research and Scholarly Interests


My career has been devoted to understanding the neural mechanisms involved in brain aging and brain plasticity, with a special focus on early detection and prevention of Alzheimer’s disease (AD). My research approach integrates principles and findings from cognitive theory, clinical neuroscience, and computational neuroscience. This approach is complemented by my extensive research experience involving multi-modality neuroimaging (PET, sMRI, dMRI, and fMRI), psychophysiology, neuropsychology, and quantitative research methods. I currently lead an interdisciplinary clinical neuroscience lab, covering a wide spectrum of research from Phases 0-2 in three areas: (a) brain aging, focusing on the links between brain pathophysiology and clinical symptoms, in a wide range of populations, from older adults with superior cognitive capacity to preclinical and prodromal AD, with an overarching aim to gain insights into the broad mechanisms of aging, both in typical and atypical populations and to identify early biomarkers for AD; (b) novel non- pharmacological interventions that promote successful cognitive aging as well as alleviate or eliminate adverse effects of AD pathophysiology; and (c) advanced computational models (e.g., explainable AI) for understanding and intervening on brain aging.

Clinical Trials


  • Breathing, Relaxation, Attention Training, & Health in Older Adults (BREATHE) Recruiting

    A recently completed study suggested that processing speed and attention (PS/A) oriented cognitive training (VSOP) produced robust effect on PS/A and working memory, but not in cognitive control or episodic memory, and long-term effects were overall modest. The proposed R01 renewal proposes to identify additional attributes to further enhance transferred and long-term effects of PS/A training in older adults with amnestic mild cognitive impairment (MCI) by addressing adaptation capacity that underpins adaptive learning and neuroplasticity. The goal of the stage II double-blinded randomized trial is to test whether adding resonance frequency breathing (RFB) training to VSOP will strengthen multiple contributors to adaptation capacity, particularly the central and peripheral pathways of autonomic nervous system (ANS) flexibility, which will strengthen VSOP training effect on cognitive and brain function and slow the progress of dementia in MCI. The central hypothesis is that strengthening adaptation capacity, via improving autonomic nervous system (ANS) flexibility, will enhance neuroplasticity and slow progress of dementia in MCI, since adaptation capacity is critical for neuroplasticity of VSOP, but compromised in neurodegenerative process. Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a waitlist IR control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility and multiple markers of dementia progress. Data will be collected across a 14-month period. The two primary aims are to examine long-term effects of the combined intervention on ANS flexibility (Aim 1), as well as the cognitive, behavioral, and functional capacity (Aim 2). The exploratory aim will be to determine the preliminary long-term effect of the combined intervention on neurodegeneration. This can be a reasonable renewal plan from the completed study, aiming to identify additional attributes to further enhance transferred and long-term effects of cognitive training in MCI. This will be among the first randomized controlled trials to examine a novel, combined intervention targeting adaptation capacity in MCI, with an ultimate goal for slowing neurodegeneration.

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  • CogT BEEM Study (a tDCS Study) Recruiting

    Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared neural circuit the investigators previously discovered and various NPS. The investigators will modify a key region within the NPS-shared neural circuit [i.e. left precentral gyrus (LPG), critical for regulating visual attention] with anodal transcranial direct current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial design the investigators will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which is considered the most detrimental type of NPS in MCI. The investigators will assign participants to 4-week active anodal vs. sham LPG online tDCS group. The investigators will assess resting-state and visual attention task-related functional MRI and informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS. Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.

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  • Applying a Person-Centered Approach to Enhance Cognitive Training in Senior Living Community Residents With Mild Cognitive Impairment Not Recruiting

    Computerized cognitive interventions (CCIs) have been increasingly widely implemented among older adults with mild cognitive impairment (MCI). However, the efficacy of CCIs in maintaining or improving older adults' cognitive and functional health has been modest and highly variable. Older individuals' attitudes toward technology use may help explain some of the variability in CCI effects. The goal of this R21 is to generate proof-of-concept for an intervention that may improve attitudes toward computers among those with MCI, in turn improving engagement with and efficacy of a subsequent CCI. Person-centered care-that is, integrating individuals' preferences throughout the process of intervention--has improved intervention engagement among older persons, including those with MCI. A recent intervention predicated on this person-centered approach is called "personalized engagement program" (PEP). PEP involves a database of individualized computer-led leisure activities. The investigators' recent pilot data in senior living facilities suggest that PEP promotes psychological well-being among older persons with MCI, and may shift computers from dauntingly complex or personally irrelevant devices to familiar, enjoyable technology. These results are consistent with a number of theories indicating that exposure to pleasurable experiences with an object or task improves several dimensions of attitudes, including affective and cognitive components, as well as behavior and motivation. Grounded in both this pilot data and the theory around it, the investigators seek to take the next step in an arc of research ultimately intended to improve the efficacy of CCIs. A small randomized controlled trial (RCT) is proposed to assess whether an initial period of PEP, followed by a standard CCI, improves a) attitudes toward computers, b) engagement with the CCI, and c) cognitive outcomes, compared to an attention control period followed by CCI. Our design involving stratified random assignment of 50 assisted living residents with MCI from 4 senior living facilities to these two groups. The initial phase involves 4 weeks of either attention control or PEP, a "dose" suggested by prior work on attitude change and computers, followed by 6 weeks of CCI for both groups (a period our prior work indicates is sufficient for change in key cognitive domains among this population). This application is the first of which we are aware striving to augment CCIs, which are now ubiquitous, by addressing an attitudinal or affective element of the person, which are often ignored in the cognitive intervention literature. The adjuvant of PEP also answers increasing calls for "personalized" or "person-centered" behavioral interventions with older persons.

    Stanford is currently not accepting patients for this trial.

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  • HARP-Project 1 Cognitive Training Not Recruiting

    Emerging evidence from social neuroscience suggests that prefrontal cortex (PFC), insular and anterior cingulate cortex (ACC) regulate social and emotional responses to acute threats to social connectedness among young adults. Deficient neural reserve or overused neural compensation resulting from neurodegeneration is commonly observed in these frontal regions in old age. This aging-related "neural depletion" may have implications for how older adults respond to social threats, potentially increasing maladaptive emotional and social behavioral responses, such as social anxiety and social avoidance, which contribute to social disconnectedness. The central hypothesis is that cognitive deficits and associated aging-related 'neural depletion' in the frontal regions will contribute to maladaptive social-emotional responses to a social stressor -- social exclusion. Ultimately, maladaptive responses to acute social stress, such as social anxiety and avoidance, can compromise social connectedness by increasing social strain and isolation. The investigators have recently developed a neuroplasticity-based cognitive training program, called vision-based speed of processing (VSOP) training, targeting multiple aspects of cognitive capacity (e.g., attention, working memory and inhibition) and incorporating the speed component to improve the efficiency of these cognitive processes. VSOP training also targets several neural networks seeded in ACC and insular (default mode network) or PFC (the frontal-striatal network and central executive network). These networks also overlap with neural substrates of emotion regulation. Notably, VSOP training appears to improve emotion regulation, as depressive symptoms were reduced in older adults following VSOP training. Finally, the autonomic nervous system (ANS), critical to stress adaptation, is regulated by these frontal regions. The objective of the proposed pilot study is to provide proof-of-concept for the hypothesis that improvements in older adults' cognitive capacity, frontal regions' neural efficiency, and ANS function via the VSOP training will be associated with more adaptive social-emotional response to social exclusion, which, in turn, should confer longer-term protection for older adults' sense of social connectedness. Randomized Controlled Trial Design: 30 older adults will be randomly assigned to engage in 6-week VSOP training, or to an active control group. Differential changes from baseline to post-training in cognitive capacity, neural efficiency, and ANS function, and sense of social connectedness, will be compared between VSOP control groups. A social exclusion paradigm ('cyberball' task) will be conducted post-training to evaluate VSOP training effects on social-emotional responses to social exclusion, including anxiety and motivation for social affiliation.

    Stanford is currently not accepting patients for this trial.

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  • Vision-based Speed of Processing Cognitive Training and Mild Cognitive Impairment Not Recruiting

    This project seeks to identify neural changes that occur in adults with mild cognitive impairment (MCI) after engagement in computerized cognitive training. In addition, this project aims to identify physiological factors that may bolster effects of the training on cognitive function. Individuals with MCI are at high risk for Alzheimer's disease (AD). Understanding how cognitive training protects cognitive function in MCI can contribute to development of effective interventions to slow progression to AD in individuals at risk, thereby reducing the significant morbidity and health care costs associated with AD.

    Stanford is currently not accepting patients for this trial.

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Stanford Advisees


All Publications


  • Enhancing Cortical Network-level Participation Coefficient as a Potential Mechanism for Transfer in Cognitive Training in aMCI. NeuroImage Chen, Q., Turnbull, A., Cole, M., Zhang, Z., Lin, F. V. 2022: 119124

    Abstract

    Effective cognitive training must improve cognition beyond the trained domain (show a transfer effect) and be applicable to dementia-risk populations, e.g., amnesic mild cognitive impairment (aMCI). Theories suggest training should target processes that 1) show robust engagement, 2) are domain-general, and 3) reflect long-lasting changes in brain organization. Brain regions that connect to many different networks (i.e., show high participation coefficient; PC) are known to support integration. This capacity is 1) relatively preserved in aMCI, 2) required across a wide range of cognitive domains, and 3) trait-like. In 49 individuals with aMCI that completed a 6-week visual speed of processing training (VSOP) and 28 active controls, enhancement in PC was significantly more related to transfer to working memory at global and network levels in VSOP compared to controls, particularly in networks with many high-PC nodes. This suggests that enhancing brain integration may provide a target for developing effective cognitive training.

    View details for DOI 10.1016/j.neuroimage.2022.119124

    View details for PubMedID 35331866

  • Age-related changes in ongoing thought relate to external context and individual cognition. Consciousness and cognition Turnbull, A., Poerio, G. L., Ho, N. S., Martinon, L. M., Riby, L. M., Lin, F. V., Jefferies, E., Smallwood, J. 2021; 96: 103226

    Abstract

    Understanding how age-related changes in cognition manifest in the real world is an important goal. One means of capturing these changes involves "experience sampling" participant's self-reported thoughts. Research has shown age-related changes in ongoing thought: e.g., older adults have fewer thoughts unrelated to the here-and-now. However, it is currently unclear how these changes reflect cognitive aging or lifestyle changes. 78 younger adults and 35 older adults rated their thought contents along 20 dimensions and the difficulty of their current activity in their daily lives. They also performed cognitive tasks in the laboratory. In a set of exploratory analyses, we found that older adults spent more time thinking positive, wanted thoughts, particularly in demanding contexts, and less time mind wandering about their future selves. Past-related thought related to episodic memory differently in older and younger adults. These findings inform the use of experience sampling to understand cognitive aging.

    View details for DOI 10.1016/j.concog.2021.103226

    View details for PubMedID 34689074

  • Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial. Trials Lin, F. V., Heffner, K., Gevirtz, R., Zhang, Z., Tadin, D., Porsteinsson, A. 2021; 22 (1): 560

    Abstract

    IMPORTANCE: Cognitive training with components that can further enhance the transferred and long-term effects and slow the progress of dementia is needed for preventing dementia.OBJECTIVE: The goal of the study is to test whether improving autonomic nervous system (ANS) flexibility via a resonance frequency breathing (RFB) training will strengthen the effects of a visual speed of processing (VSOP) cognitive training on cognitive and brain function, and slow the progress of dementia in older adults with mild cognitive impairment (MCI).DESIGN: Stage II double-blinded randomized controlled trial. The study was prospectively registered at ClinicalTrials.gov, with registration approved on 21 August 2020 (No. NCT04522791).SETTING: Study-related appointments will be conducted on-site at University of Rochester Medical Center locations. Data collection will be conducted from August 2020 to February 2025.PARTICIPANTS: Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a IR-only control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility, measured by heart rate variability, and multiple markers of dementia progress. Data will be collected across a 14-month period.DISCUSSION: This will be among the first RCTs to examine in older persons with MCI a novel, combined intervention targeting ANS flexibility, an important contributor to overall environmental adaptation, with an ultimate goal for slowing neurodegeneration.TRIAL REGISTRATION: ClinicalTrials.gov NCT04522791 . Registered on 21 August 2020 Protocol version: STUDY00004727; IRB protocol version 2, approved on 30 July 2020.

    View details for DOI 10.1186/s13063-021-05530-z

    View details for PubMedID 34425878

  • Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training HUMAN BRAIN MAPPING Chen, Q., Baran, T. M., Turnbull, A., Zhang, Z., Rebok, G. W., Lin, F. 2021

    Abstract

    A major challenge in the cognitive training field is inducing broad, far-transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision-based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non-learners) and a subset of participants in the MLA (i.e., MLA non-learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.

    View details for DOI 10.1002/hbm.25428

    View details for Web of Science ID 000647414100001

    View details for PubMedID 33955088

  • ONLINE, COMPUTERIZED BRAIN TRAINING TO PROMOTE STRESS ADAPTATION AND IMMUNE HEALTH IN CAREGIVERS OF A FAMILY MEMBER WITH DEMENTIA: RATIONALE AND ENGAGEMENT DATA FROM AN ONGOING CLINICAL TRIAL Heffner, K. L., Swan, J., Quinones, M., Gallegos, A., Lin, F. OXFORD UNIV PRESS INC. 2021: S546
  • Subjective memory in adults over 50 years of age: associations with affective and physiological markers of emotion regulation AGING & MENTAL HEALTH Heffner, K. L., Quinones, M. M., Gallegos, A. M., Crean, H. F., Lin, F., Suhr, J. A. 2021: 1-9

    Abstract

    To examine associations among subjective memory reports, psychophysiological markers of emotion regulation, and cognitive performance in healthy adults over 50 years of age.A cross-sectional laboratory study was conducted with healthy, community-dwelling, non-depressed adults (M age = 60.4 years, SD = 8.4). The Metamemory in Adulthood (MIA) questionnaire provided reports of subjective memory capacity and stability (versus decline) and anxiety about memory. Poorer emotion regulation was marked by greater negative affect (NA) and lower high frequency heart rate variability (HF-HRV) responses to a challenging working memory task. Regression models were used to identify associations between subjective memory and emotion regulation markers, and structural equation modeling was used to explore whether emotion regulation mediated associations between subjective memory and objective task performance.A total of 115 participants were included in the final sample. Subjective memory decline (indicated by lower scores on memory stability) was associated with lower HF-HRV response and worse working memory performance. Poorer subjective memory capacity and more anxiety about memory were both associated with greater negative affect in response to the working memory task. There was an indirect effect of subjective memory capacity on working memory performance through negative affect response.The findings here suggest that worse subjective memory may signal reduced capacity for emotion regulation. Along with known cognitive risks of depression and anxiety, more subtle emotion regulation difficulties may be involved in pathways of poor cognitive aging.

    View details for DOI 10.1080/13607863.2021.1904829

    View details for Web of Science ID 000635019000001

    View details for PubMedID 33784222

  • Brain Small-Worldness Properties and Perceived Fatigue in Mild Cognitive Impairment. The journals of gerontology. Series A, Biological sciences and medical sciences Kukla, B., Anthony, M., Chen, S., Turnbull, A., Baran, T. M., Lin, F. V. 2021

    Abstract

    BACKGROUND: Perceived fatigue is among the most common complaints in older adults and is substantially influenced by diminished resources or impaired structure of widespread cortical and subcortical regions. Alzheimer's disease and its preclinical stage - mild cognitive impairment (MCI) - is considered a brain network disease. It is unknown, however, whether those with MCI will therefore perceive worse fatigue, and whether an impaired global brain network will worsen their experience of fatigue.METHODS: In this pilot case-control study of age-, sex-, and education-matched MCI and their cognitively healthy counterparts (HC), perceived fatigue was measured using Multidimensional Fatigue Inventory, and diffusion tensor imaging (DTI) tractography data was analyzed using graph theory methods to explore small-worldness properties: segregation and integration.RESULTS: Perceived fatigue was more severe in MCI than HC. Despite a trend for greater network alterations in MCI, there were no significant group differences in integration or segregation. Greater perceived fatigue was related to higher segregation across groups; more perceived fatigue was related to higher segregation and lower integration in MCI but not HC.CONCLUSIONS: Findings of the present study support the notion that altered whole-brain small-worldness properties in brain aging or neurodegeneration may underpin perceived fatigue.

    View details for DOI 10.1093/gerona/glab084

    View details for PubMedID 33733662

  • Attitudes Toward Computers Moderate the Effect of Computerized Cognitive Trainings in Oldest-Old Senior Living Center Residents AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Lin, F., Cottone, K., Mcdermott, K., Jacobs, A., Nelson, D., Porsteinsson, A., Chapman, B. P. 2021; 29 (3): 285-294

    Abstract

    Computerized cognitive interventions (CCIs) have been increasingly implemented among older adults with mild cognitive impairment (MCI). However, older individuals' attitudes toward technology may limit CCI engagement. This exploratory-developmental study examined whether a "multi-functional interactive computer system" (MICS), which provides pleasurable activities via computer, would improve attitudes toward computers and in turn increase the efficacy of a subsequent CCI.A phase one double-blind trial randomized 49 seniors with MCI to a MICS + CCI condition or a CCI-only condition. Attitudes toward technology use was assessed using The Attitudes Toward Computers Questionnaire (ATCQ), and cognition was assessed using episodic memory and executive function composite scores at baseline, the ends of MICS and CCI phases, and 3-month follow-up.The MICS + CCI group did not show significantly greater improvement in cognition than the CCI only group. Secondary analyses indicated that improvement in executive function from baseline occurred in both groups. Participants who did show improved attitudes toward computers, whether through MICS or simply computer exposure itself, showed improvement in executive function.Participants in the MICS + CCI group used MICS less than expected. A more structured and supervised approach may be needed to facilitate MICS exposure. Improved attitudes toward computers regardless of MICS exposure may benefit candidates for CCI.

    View details for DOI 10.1016/j.jagp.2020.07.001

    View details for Web of Science ID 000632041300011

    View details for PubMedID 32739240

  • Learning Clique Subgraphs in Structural Brain Network Classification with Application to Crystallized Cognition NEUROIMAGE Wang, L., Lin, F., Cole, M., Zhang, Z. 2021; 225: 117493

    Abstract

    Structural brain networks constructed from diffusion MRI are important biomarkers for understanding human brain structure and its relation to cognitive functioning. There is increasing interest in learning differences in structural brain networks between groups of subjects in neuroimaging studies, leading to a variable selection problem in network classification. Traditional methods often use independent edgewise tests or unstructured generalized linear model (GLM) with regularization on vectorized networks to select edges distinguishing the groups, which ignore the network structure and make the results hard to interpret. In this paper, we develop a symmetric bilinear logistic regression (SBLR) with elastic-net penalty to identify a set of small clique subgraphs in network classification. Clique subgraphs, consisting of all the interconnections among a subset of brain regions, have appealing neurological interpretations as they may correspond to some anatomical circuits in the brain related to the outcome. We apply this method to study differences in the structural connectome between adolescents with high and low crystallized cognitive ability, using the crystallized cognition composite score, picture vocabulary and oral reading recognition tests from NIH Toolbox. A few clique subgraphs containing several small sets of brain regions are identified between different levels of functioning, indicating their importance in crystallized cognition.

    View details for DOI 10.1016/j.neuroimage.2020.117493

    View details for Web of Science ID 000600797900046

    View details for PubMedID 33127479

    View details for PubMedCentralID PMC7826449

  • Functional brain mapping in patients with chronic back pain shows age-related differences. Pain Baran, T. M., Lin, F. V., Geha, P. 2021

    Abstract

    Low back-pain is the most common pain condition and cause for disability in older adults. Older adults suffering from low-back pain are more disabled than their healthy peers, are more predisposed to frailty, and tend to be undertreated. The cause of increased prevalence and severity of this chronic pain condition in older adults is unknown. Here we draw on accumulating data demonstrating a critical role for brain limbic and sensory circuitries in the emergence and experience of chronic low-back pain (CLBP) and the availability of resting state brain activity data collected at different sites to study how brain activity patterns predictive of CLBP differ between age groups. We apply a data driven multivariate searchlight analysis to amplitude of low-frequency fluctuation brain maps to classify CLBP patients with > 70% accuracy. We observe that brain activity pattern including the paracingulate gyrus, insula/SII, inferior frontal, temporal, and fusiform gyrus predicted CLBP. When separated by age groups, brain patterns predictive of older CLBP patients showed extensive involvement of limbic brain areas including the ventro-medial prefrontal cortex, the nucleus accumbens and hippocampus, whereas only anterior insula paracingulate and fusiform gyrus predicted CLBP in the younger patients. In addition, we validated the relationships between back-pain intensity ratings and CLBP brain activity patterns in an independent data set not included in our initial patterns' identification. Our results are the first to directly address how aging affects the neural signature of CLBP and point to an increased role of limbic brain areas in older CLBP patients.

    View details for DOI 10.1097/j.pain.0000000000002534

    View details for PubMedID 34799532

  • Longitudinal stability of medial temporal lobe connectivity is associated with tau-related memory decline ELIFE Chen, Q., Turnbull, A., Baran, T. M., Lin, F. 2020; 9

    Abstract

    The relationship between Alzheimer's disease (AD) pathology and cognitive decline is an important topic in the aging research field. Recent studies suggest that memory deficits are more susceptible to phosphorylated tau (Ptau) than amyloid-beta. However, little is known regarding the neurocognitive mechanisms linking Ptau and memory-related decline. Here, we extracted data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with cerebrospinal fluid (CSF) Ptau collected at baseline, diffusion tensor imaging measure twice, 2 year apart, and longitudinal memory data over 5 years. We defined three age- and education-matched groups: Ptau negative cognitively unimpaired, Ptau positive cognitively unimpaired, and Ptau positive individuals with mild cognitive impairment. We found the presence of CSF Ptau at baseline was related to a loss of structural stability in medial temporal lobe connectivity in a way that matched proposed disease progression, and this loss of stability in connections known to be important for memory moderated the relationship between Ptau accumulation and memory decline.

    View details for DOI 10.7554/eLife.62114

    View details for Web of Science ID 000610837100001

    View details for PubMedID 33382038

    View details for PubMedCentralID PMC7803375

  • Brain structural connectomes indicate shared neural circuitry involved in subjective experience of cognitive and physical fatigue in older adults BRAIN IMAGING AND BEHAVIOR Baran, T. M., Zhang, Z., Anderson, A., McDermott, K., Lin, F. 2020; 14 (6): 2488-2499

    Abstract

    Cumulative evidence suggests the existence of common processes underlying subjective experience of cognitive and physical fatigue. However, mechanistic understanding of the brain structural connections underlying the experience of fatigue in general, without the influence of clinical conditions, is limited. The purpose of the study was to examine the relationship between structural connectivity and perceived state fatigue in older adults. We enrolled cognitively and physically healthy older individuals (n = 52) and categorized them into three groups (low cognitive/low physical fatigue; low cognitive/high physical fatigue; high cognitive/low physical fatigue; no subjects had high cognitive/high physical fatigue) based on perceived fatigue from cognitive and physical fatigue manipulation tasks. Using sophisticated diffusion tensor imaging processing techniques, we extracted connectome matrices for six different characteristics of whole-brain structural connections for each subject. Tensor network principal component analysis was used to examine group differences in these connectome matrices, and extract principal brain networks for each group. Connected surface area of principal brain networks differentiated the two high fatigue groups from the low cognitive/physical fatigue group (high vs. low physical fatigue, p = 0.046; high vs. low cognitive fatigue, p = 0.036). Greater connected surface area within striatal-frontal-parietal networks was correlated with lower cognitive and physical fatigue, and was predictive of perceived physical and cognitive fatigue measures not used for group categorization (Pittsburgh fatigability physical subscale, R2 = 0.70, p < 0.0001; difference in self-report fatigue before and after gambling tasks, R2 = 0.54, p < 0.0001). There are potentially structural connectomes resilient to both cognitive and physical fatigue in older adults.

    View details for DOI 10.1007/s11682-019-00201-9

    View details for Web of Science ID 000587138100035

    View details for PubMedID 31493140

    View details for PubMedCentralID PMC7058488

  • Decoding individual identity from brain activity elicited in imagining common experiences NATURE COMMUNICATIONS Anderson, A., McDermott, K., Rooks, B., Heffner, K. L., Dodell-Feder, D., Lin, F. V. 2020; 11 (1): 5916

    Abstract

    Everyone experiences common events differently. This leads to personal memories that presumably provide neural signatures of individual identity when events are reimagined. We present initial evidence that these signatures can be read from brain activity. To do this, we progress beyond previous work that has deployed generic group-level computational semantic models to distinguish between neural representations of different events, but not revealed interpersonal differences in event representations. We scanned 26 participants' brain activity using functional Magnetic Resonance Imaging as they vividly imagined themselves personally experiencing 20 common scenarios (e.g., dancing, shopping, wedding). Rather than adopting a one-size-fits-all approach to generically model scenarios, we constructed personal models from participants' verbal descriptions and self-ratings of sensory/motor/cognitive/spatiotemporal and emotional characteristics of the imagined experiences. We demonstrate that participants' neural representations are better predicted by their own models than other peoples'. This showcases how neuroimaging and personalized models can quantify individual-differences in imagined experiences.

    View details for DOI 10.1038/s41467-020-19630-y

    View details for Web of Science ID 000595687700012

    View details for PubMedID 33219210

    View details for PubMedCentralID PMC7679397

  • Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis PSYCHOPHYSIOLOGY Koenig, J., Abler, B., Agartz, I., akerstedt, T., Andreassen, O. A., Anthony, M., Baer, K., Bertsch, K., Brown, R. C., Brunner, R., Carnevali, L., Critchley, H. D., Cullen, K. R., de Geus, E. C., de la Cruz, F., Dziobek, I., Ferger, M. D., Fischer, H., Flor, H., Gaebler, M., Gianaros, P. J., Giummarra, M. J., Greening, S. G., Guendelman, S., Heathers, J. J., Herpertz, S. C., Hu, M. X., Jentschke, S., Kaess, M., Kaufmann, T., Klimes-Dougan, B., Koelsch, S., Krauch, M., Kumral, D., Lamers, F., Lee, T., Lekander, M., Lin, F., Lotze, M., Makovac, E., Mancini, M., Mancke, F., Mansson, K. T., Manuck, S. B., Mather, M., Meeten, F., Min, J., Mueller, B., Muench, V., Nees, F., Nga, L., Nilsonne, G., Ordonez Acuna, D., Osnes, B., Ottaviani, C., Penninx, B. H., Ponzio, A., Poudel, G. R., Reinelt, J., Ren, P., Sakaki, M., Schumann, A., Sorensen, L., Specht, K., Straub, J., Tamm, S., Thai, M., Thayer, J. F., Ubani, B., van Der Mee, D. J., van Velzen, L. S., Ventura-Bort, C., Villringer, A., Watson, D. R., Wei, L., Wendt, J., Schreiner, M., Westlye, L. T., Weymar, M., Winkelmann, T., Wu, G., Yoo, H., Quintana, D. S. 2020

    Abstract

    Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

    View details for DOI 10.1111/psyp.13688

    View details for Web of Science ID 000579312100001

    View details for PubMedID 33037836

  • Autonomic flexibility reflects learning and associated neuroplasticity in old age HUMAN BRAIN MAPPING Chen, Q., Yang, H., Rooks, B., Anthony, M., Zhang, Z., Tadin, D., Heffner, K. L., Lin, F. 2020; 41 (13): 3608-3619

    Abstract

    Effective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659-676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG-derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6-week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross-participant and cross-task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training-induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training).

    View details for DOI 10.1002/hbm.25034

    View details for Web of Science ID 000538566700001

    View details for PubMedID 32510759

    View details for PubMedCentralID PMC7416041

  • Processing speed and attention training modifies autonomic flexibility: A mechanistic intervention study NEUROIMAGE Lin, F., Tao, Y., Chen, Q., Anthony, M., Zhang, Z., Tadin, D., Heffner, K. L. 2020; 213: 116730

    Abstract

    Adaptation capacity is critical for maintaining cognition, yet it is understudied in groups at risk for dementia. Autonomic nervous system (ANS) is critical for neurovisceral integration and is a key contributor to adaptation capacity. To determine the central nervous system's top-down regulation of ANS, we conducted a mechanistic randomized controlled trial study, using a 6-week processing speed and attention (PS/A)-targeted intervention. Eighty-four older adults with amnestic mild cognitive impairment (aMCI) were randomized to a 6-week PS/A-targeted intervention or an active control without PS/A. Utilizing repeated measures (i.e., PS/A test different from the intervention, resting and cognitive task-based ECG, and resting fMRI) at baseline, immediately post-intervention (post-test), and 6-month follow-up, we aimed to test whether PS/A causally influences vagal control of ANS via their shared central neural pathways in aMCI. We indexed vagal control of ANS using high-frequency heart rate variability (HF-HRV) extracted from ECG data. Functional brain connectivity patterns were extracted from fMRI using advanced statistical tools. Compared to the control group, the intervention group showed significant improvement in PS/A, HF-HRV, salience network (SN), central executive network (CEN), and frontal parietal network (FPN) connectivity at post-test; the effect on SN, CEN, and FPN remained at 6-month follow-up. Changes in PS/A and SN connectivity significantly predicted change in HF-HRV from baseline to post-test and/or 6-month-follow-up. Age, neurodegeneration, nor sex did not affect these relationships. This work provides novel support for top-down regulation of PS/A and associated SN on vagal control of ANS. Intervening PS/A may be a viable approach for promoting adaptation capacity in groups at risk for dementia.

    View details for DOI 10.1016/j.neuroimage.2020.116730

    View details for Web of Science ID 000525321000026

    View details for PubMedID 32165263

    View details for PubMedCentralID PMC7165056

  • Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE Quinones, M. M., Gallegos, A. M., Lin, F., Heffner, K. 2020; 20 (3): 455-480

    Abstract

    Compelling evidence from animal and human research suggest a strong link between inflammation and posttraumatic stress disorder (PTSD). Furthermore, recent findings support compromised neurocognitive function as a key feature of PTSD, particularly with deficits in attention and processing speed, executive function, and memory. These cognitive domains are supported by brain structures and neural pathways that are disrupted in PTSD and which are implicated in fear learning and extinction processes. The disruption of these supporting structures potentially results from their interaction with inflammation. Thus, the converging evidence supports a model of inflammatory dysregulation and cognitive dysfunction as combined mechanisms underpinning PTSD symptomatology. In this review, we summarize evidence of dysregulated inflammation in PTSD and further explore how the neurobiological underpinnings of PTSD, in the context of fear learning and extinction acquisition and recall, may interact with inflammation. We then present evidence for cognitive dysfunction in PTSD, highlighting findings from human work. Potential therapeutic approaches utilizing novel pharmacological and behavioral interventions that target inflammation and cognition also are discussed.

    View details for DOI 10.3758/s13415-020-00782-9

    View details for Web of Science ID 000537454400001

    View details for PubMedID 32170605

    View details for PubMedCentralID PMC7682894

  • A generic brain connectome map linked to different types of everyday decision-making in old age BRAIN STRUCTURE & FUNCTION Rooks, B., Anthony, M., Chen, Q., Lin, Y., Baran, T., Zhang, Z., Lichtenberg, P. A., Li, F. 2020; 225 (4): 1389-1400

    Abstract

    Making reasonable decisions related to financial and health scenarios is a crucial capacity that can be difficult for older adults to maintain as they age, yet few studies examine neurocognitive factors that are generalizable to different types of everyday decision-making capacity. Here we propose an innovative approach, based on individual risk-taking preference, to identify neural profiles that may help predict older adults' everyday decision-making capacity. Using performance and cognitive arousal information from two gambling tasks, we identified three decision-making preference groups: ambiguity problem-solvers (A), risk-seekers (R), and a control group without strong risk-taking preferences (C). Comparisons of the number of connections within white matter tracts between A vs. C and R vs. C groups resulted in features consistent with the theory of dual neural functional systems involved in decision-making. Unique tracts from the A vs. C contrast were primarily centered in dorsal frontal regions/reflective system; unique tracts from the R vs. C contrast were centered in the ventral frontal regions/impulsive system; and shared tracts from both contrasts were centered in the basal ganglia, coordinating the switch between the two types of decision-making preference. Number of connections from the tracts differentiating A vs. C significantly predicted financial and health/safety decision-making capacity, and the association remained significant after controlling for multiple socioeconomic and cognitive factors. The connectome identified may provide insight into a generic white matter mechanism related to everyday decision-making capacity in older age.

    View details for DOI 10.1007/s00429-019-02013-5

    View details for Web of Science ID 000537779200014

    View details for PubMedID 31858236

    View details for PubMedCentralID PMC7274871

  • Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial) TRIALS Li, D., Mielke, M. M., Bell, W., Reilly, C., Zhang, L., Lin, F., Yu, F. 2020; 21 (1): 19

    Abstract

    Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia.The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months.This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia.ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.

    View details for DOI 10.1186/s13063-019-3798-1

    View details for Web of Science ID 000514647500020

    View details for PubMedID 31907024

    View details for PubMedCentralID PMC6943901

  • Cognitively supernormal older adults maintain a unique structural connectome that is resistant to Alzheimer's pathology NEUROIMAGE-CLINICAL Chen, Q., Baran, T. M., Rooks, B., O'Banion, M., Mapstone, M., Zhang, Z., Lin, F., Alzheimers Dis Neuroimaging 2020; 28: 102413

    Abstract

    Studying older adults with excellent cognitive capacities (Supernormals) provides a unique opportunity for identifying factors related to cognitive success - a critical topic across lifespan. There is a limited understanding of Supernormals' neural substrates, especially whether any of them attends shaping and supporting superior cognitive function or confer resistance to age-related neurodegeneration such as Alzheimer's disease (AD). Here, applying a state-of-the-art diffusion imaging processing pipeline and finite mixture modelling, we longitudinally examine the structural connectome of Supernormals. We find a unique structural connectome, containing the connections between frontal, cingulate, parietal, temporal, and subcortical regions in the same hemisphere that remains stable over time in Supernormals, relatively to typical agers. The connectome significantly classifies positive vs. negative AD pathology at 72% accuracy in a new sample mixing Supernormals, typical agers, and AD risk [amnestic mild cognitive impairment (aMCI)] subjects. Among this connectome, the mean diffusivity of the connection between right isthmus cingulate cortex and right precuneus most robustly contributes to predicting AD pathology across samples. The mean diffusivity of this connection links negatively to global cognition in those Supernormals with positive AD pathology. But this relationship does not exist in typical agers or aMCI. Our data suggest the presence of a structural connectome supporting cognitive success. Cingulate to precuneus white matter integrity may be useful as a structural marker for monitoring neurodegeneration and may provide critical information for understanding how some older adults maintain or excel cognitively in light of significant AD pathology.

    View details for DOI 10.1016/j.nicl.2020.102413

    View details for Web of Science ID 000600619100056

    View details for PubMedID 32971466

    View details for PubMedCentralID PMC7511768

  • An Integrated Neural Decoder of Linguistic and Experiential Meaning JOURNAL OF NEUROSCIENCE Anderson, A., Binder, J. R., Fernandino, L., Humphries, C. J., Conant, L. L., Raizada, R. S., Lin, F., Lalor, E. C. 2019; 39 (45): 8969-8987

    Abstract

    The brain is thought to combine linguistic knowledge of words and nonlinguistic knowledge of their referents to encode sentence meaning. However, functional neuroimaging studies aiming at decoding language meaning from neural activity have mostly relied on distributional models of word semantics, which are based on patterns of word co-occurrence in text corpora. Here, we present initial evidence that modeling nonlinguistic "experiential" knowledge contributes to decoding neural representations of sentence meaning. We model attributes of peoples' sensory, motor, social, emotional, and cognitive experiences with words using behavioral ratings. We demonstrate that fMRI activation elicited in sentence reading is more accurately decoded when this experiential attribute model is integrated with a text-based model than when either model is applied in isolation (participants were 5 males and 9 females). Our decoding approach exploits a representation-similarity-based framework, which benefits from being parameter free, while performing at accuracy levels comparable with those from parameter fitting approaches, such as ridge regression. We find that the text-based model contributes particularly to the decoding of sentences containing linguistically oriented "abstract" words and reveal tentative evidence that the experiential model improves decoding of more concrete sentences. Finally, we introduce a cross-participant decoding method to estimate an upper bound on model-based decoding accuracy. We demonstrate that a substantial fraction of neural signal remains unexplained, and leverage this gap to pinpoint characteristics of weakly decoded sentences and hence identify model weaknesses to guide future model development.SIGNIFICANCE STATEMENT Language gives humans the unique ability to communicate about historical events, theoretical concepts, and fiction. Although words are learned through language and defined by their relations to other words in dictionaries, our understanding of word meaning presumably draws heavily on our nonlinguistic sensory, motor, interoceptive, and emotional experiences with words and their referents. Behavioral experiments lend support to the intuition that word meaning integrates aspects of linguistic and nonlinguistic "experiential" knowledge. However, behavioral measures do not provide a window on how meaning is represented in the brain and tend to necessitate artificial experimental paradigms. We present a model-based approach that reveals early evidence that experiential and linguistically acquired knowledge can be detected in brain activity elicited in reading natural sentences.

    View details for DOI 10.1523/JNEUROSCI.2575-18.2019

    View details for Web of Science ID 000495094400012

    View details for PubMedID 31570538

    View details for PubMedCentralID PMC6832686

  • Insula and putamen centered functional connectivity networks reflect healthy agers' subjective experience of cognitive fatigue in multiple tasks CORTEX Anderson, A. J., Ren, P., Baran, T. M., Zhang, Z., Lin, F. 2019; 119: 428-440

    Abstract

    Cognitive fatigue (CF) impairs ability to perform daily activities, is a common complaint of aging and a symptom of multiple neurological conditions. However, knowledge of the neural basis of CF is limited. This is partially because CF is difficult to systematically modulate in brain imaging experiments. The most common approach has been to scan brain activity during effortful cognitive tasks. Consequently, neural correlates of CF tend to be task-specific and may vary across tasks. This makes it difficult to know how results generalize across studies and is outside the subjective experience of CF which tends to be similar in different tasks. It has been hypothesized that the subjective experience of CF might arise from domain general systems monitoring and acting on energy depletion in task specific circuits. Direct supporting neural evidence is lacking. By repeatedly scanning aging individuals undertaking four different tasks using functional Magnetic Resonance Imaging and referencing scans to detailed CF self-ratings taken before and after scanning, we sought task-general correlates of CF. We ran a data-driven representational similarity analysis, treating each brain region as a candidate CF functional connectivity hub, and correlating inter-participant differences in hub-based connectivity patterns with inter-participant differences in self-rated CF-profiles (a pattern of ratings across 18 questions). Both right insula and right putamen-based network connectivity patterns reflected CF across all tasks and could underpin subjective experience of CF.

    View details for DOI 10.1016/j.cortex.2019.07.019

    View details for Web of Science ID 000489035600033

    View details for PubMedID 31499435

    View details for PubMedCentralID PMC6783365

  • Stress adaptation in older adults with and without cognitive impairment: an fMRI pattern-based similarity analysis AGING-US Wang, X., Heffner, K. L., Anthony, M., Lin, F. 2019; 11 (17): 6792-6804

    Abstract

    The capacity to adapt to environmental stressors is essential for older adults' health and well-being. It is unclear how cognitive impairment may disrupt the capacity. Here we examined the relationship between self-perceptions of stress and the neurobiological response to a laboratory model of stress adaptation in amnestic mild cognitive impairment (aMCI), a group at high risk for dementia.aMCI group and cognitively healthy controls did not differ in neurobiological acute stress recovery (indexed by similarity in neural patterns at baseline and after recovery from cognitive challenges). However, compared to controls, aMCI group had significantly lower scores on PSS-PW. Notably, higher PSS-PW was associated with greater acute neural recovery in controls, but not aMCI.We assessed self-perceptions of stress adaptation with the Perceived Stress Scale subscales, measuring perceived helplessness (i.e., negatively worded items, PSS-NW) and self-efficacy (i.e., positively worded items, PSS-PW) in response to stress. At a subsequent laboratory fMRI visit, we indexed neurobiological stress adaptation by assessing and comparing functional network connectivity at baseline and immediately following, and after recovery from, cognitive challenges.Studying stress adaptation in aMCI may shed light on pathways that contribute to the onset and progress of cognitive deterioration in aging.

    View details for DOI 10.18632/aging.102204

    View details for Web of Science ID 000487978100015

    View details for PubMedID 31480017

    View details for PubMedCentralID PMC6756885

  • Multiple Regions of a Cortical Network Commonly Encode the Meaning of Words in Multiple Grammatical Positions of Read Sentences CEREBRAL CORTEX Anderson, A., Lalor, E. C., Lin, F., Binder, J. R., Fernandino, L., Humphries, C. J., Conant, L. L., Raizada, R. S., Grimm, S., Wang, X. 2019; 29 (6): 2396-2411

    Abstract

    Deciphering how sentence meaning is represented in the brain remains a major challenge to science. Semantically related neural activity has recently been shown to arise concurrently in distributed brain regions as successive words in a sentence are read. However, what semantic content is represented by different regions, what is common across them, and how this relates to words in different grammatical positions of sentences is weakly understood. To address these questions, we apply a semantic model of word meaning to interpret brain activation patterns elicited in sentence reading. The model is based on human ratings of 65 sensory/motor/emotional and cognitive features of experience with words (and their referents). Through a process of mapping functional Magnetic Resonance Imaging activation back into model space we test: which brain regions semantically encode content words in different grammatical positions (e.g., subject/verb/object); and what semantic features are encoded by different regions. In left temporal, inferior parietal, and inferior/superior frontal regions we detect the semantic encoding of words in all grammatical positions tested and reveal multiple common components of semantic representation. This suggests that sentence comprehension involves a common core representation of multiple words' meaning being encoded in a network of regions distributed across the brain.

    View details for DOI 10.1093/cercor/bhy110

    View details for Web of Science ID 000482132400007

    View details for PubMedID 29771323

  • Longitudinal Relationship Between Frailty and Cognition in Patients 50 Years and Older with Breast Cancer JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Magnuson, A., Lei, L., Gilmore, N., Kleckner, A. S., Lin, F., Ferguson, R., Hurria, A., Wittink, M. N., Esparaz, B. T., Giguere, J. K., Misleh, J., Bautista, J., Mohile, S. G., Janelsins, M. C. 2019; 67 (5): 928-936

    Abstract

    To evaluate relationships between frailty and cognition longitudinally in adults 50 years and older with breast cancer receiving chemotherapy.Secondary analysis of a prospective longitudinal observational study.University of Rochester NCI Community Oncology Research Program community oncology clinics.Patients with breast cancer age 50 and older receiving adjuvant/neoadjuvant chemotherapy (n = 376) and age-matched controls without cancer (n = 234).Frailty was assessed using a modified frailty score from self-reported assessments (weakness, exhaustion, physical activity, and gait speed). Cognition was assessed by patient report (Functional Assessment of Cancer Therapy-Cognition [FACT-Cog]) and objective measures. Frailty and cognition were measured at three time points (prechemotherapy [A1], postchemotherapy [A2], and 6 months postchemotherapy [A3]; similar time interval for controls). Linear regression models evaluated associations between frailty and cognition adjusting for covariates.The average age was 59 years (standard deviation = 6.4 y). At baseline, patients with cancer had a higher mean frailty score (1.21 vs .73; P < .001) and lower mean FACT-Cog score (158.4 vs 167.3; P < .001) compared with controls. Objective cognitive measures were not statistically different. Longitudinal decline in FACT-Cog between A1 and A2 (P < .05) and between A1 and A3 (P < .01) was associated with increased frailty score in patients compared with controls. Longitudinal worsening in Controlled Oral Word Association (P < .05) and Trail-Making Test (P < .01) were associated with an increase in frailty between A1 and A2 in patients compared with controls; longitudinal decline in the Delayed Match to Sample test was associated with an increase in frailty between A1 and A3 (P < .05) in patients compared with controls. This finding remained significant for a subset analysis of those aged 65 and older.In patients with breast cancer aged 50 and older, longitudinal decline in FACT-Cog and objective measures of attention and memory were associated with increased frailty during treatment and up to 6 months posttreatment. Overall, our study suggests cognition and frailty are both important factors to assess in breast cancer patients. J Am Geriatr Soc 67:928-936, 2019.

    View details for DOI 10.1111/jgs.15934

    View details for Web of Science ID 000466184200011

    View details for PubMedID 31034595

    View details for PubMedCentralID PMC6490967

  • Cognitive fatigue and cortical-striatal network in old age AGING-US Ren, P., Anderson, A. J., McDermott, K., Baran, T. M., Lin, F. 2019; 11 (8): 2312-2326

    Abstract

    Cognitive fatigue (CF) is among the most common and disturbing aging symptoms, and substantially interferes with activities demanding sustained mental effort. Here we examined the relationship between the cortical-striatal network and CF (assessed by the 18-item visual analogue scale) when a group of cognitively and physically healthy older adults participated in a 30-minute cognitively fatiguing task-related fMRI experiment. We also explored whether CF would interfere with the "Posterior-Anterior Shifting in Aging" (PASA) phenomenon, an aging-associated neural reliance on frontal regions to support cognitive capacity. We revealed that decreased connectivity strength of the cortical-striatal network over the course of the task was related to higher CF. Correlation between CF and the cortical-striatal network was more robust in anterior relative to posterior components. Moreover, a positive relationship between reliance on the anterior part of the cortical-striatal network and cognitive performance only existed among older adults experiencing low CF. These findings suggest a crucial role of the cortical-striatal network, especially the anterior component, in linking to CF. The PASA phenomenon may only be applicable to older adults without vulnerability to CF.

    View details for DOI 10.18632/aging.101915

    View details for Web of Science ID 000466768900012

    View details for PubMedID 30995207

    View details for PubMedCentralID PMC6519999

  • Cognitive and physical factors affecting daily function in Alzheimer's disease: A cross-sectional analysis NURSING & HEALTH SCIENCES Yu, F., Chen, Y., Mathiason, M. A., Wan, Q., Lin, F. V. 2019; 21 (1): 14-20

    Abstract

    Understanding the factors affecting activities of daily living (ADL) is important in Alzheimer's disease (AD), because decline in ADL contributes to many poor health outcomes. Existing studies often investigate the factors in isolation without a theoretical framework. The purpose of the present study was to provide preliminary results on how cognition, physical performance, and behavioral and psychological symptoms of dementia mediate the relationship of aerobic fitness and ADL in AD. A cross-sectional analysis was used (n = 28: average age 78 [8] years, education 16 (3) years, Mini-Mental State Examination scores 20 [4]). The results showed that aerobic fitness is not linked to ADL directly, and its association with ADL was mediated by physical performance and global cognition. Our findings provide preliminary support for aerobic fitness as a potential therapeutic target, as enhanced aerobic fitness could simultaneously modify other factors affecting ADL. Nurses are in a unique position for coordinating exercise safety assessment and prescription and educating older adults with AD about exercise participation.

    View details for DOI 10.1111/nhs.12426

    View details for Web of Science ID 000460079500003

    View details for PubMedID 29736953

  • The mediating role of hippocampal networks on stress regulation in amnestic mild cognitive impairment NEUROBIOLOGY OF STRESS McDermott, K., Ren, P., Lin, F. 2019; 10: 100162

    Abstract

    To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI).This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22).For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group.Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.

    View details for DOI 10.1016/j.ynstr.2019.100162

    View details for Web of Science ID 000477761300028

    View details for PubMedID 31193516

    View details for PubMedCentralID PMC6535625

  • Identify a shared neural circuit linking multiple neuropsychiatric symptoms with Alzheimer's pathology BRAIN IMAGING AND BEHAVIOR Wang, X., Ren, P., Mapstone, M., Conwell, Y., Porsteinsson, A. P., Foxe, J. J., Raizada, R. S., Lin, F., Alzheimer's Dis Neuroimaging In 2019; 13 (1): 53-64

    Abstract

    Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD)-associated neurodegeneration. However, NPS lack a consistent relationship with AD pathology. It is unknown whether any common neural circuits can link these clinically disparate while mechanistically similar features with AD pathology. Here, we explored the neural circuits of NPS in AD-associated neurodegeneration using multivariate pattern analysis (MVPA) of resting-state functional MRI data. Data from 98 subjects (70 amnestic mild cognitive impairment and 28 AD subjects) were obtained. The top 10 regions differentiating symptom presence across NPS were identified, which were mostly the fronto-limbic regions (medial prefrontal cortex, caudate, etc.). These 10 regions' functional connectivity classified symptomatic subjects across individual NPS at 69.46-81.27%, and predicted multiple NPS (indexed by Neuropsychiatric Symptom Questionnaire-Inventory) and AD pathology (indexed by baseline and change of beta-amyloid/pTau ratio) all above 70%. Our findings suggest a fronto-limbic dominated neural circuit that links multiple NPS and AD pathology. With further examination of the structural and pathological changes within the circuit, the circuit may shed light on linking behavioral disturbances with AD-associated neurodegeneration.

    View details for DOI 10.1007/s11682-017-9767-y

    View details for Web of Science ID 000460795600005

    View details for PubMedID 28913718

    View details for PubMedCentralID PMC5854501

  • How pattern information analyses of semantic brain activity elicited in language comprehension could contribute to the early identification of Alzheimer's Disease NEUROIMAGE-CLINICAL Anderson, A., Lin, F. 2019; 22: 101788

    Abstract

    Alzheimer's disease (AD) is associated with a loss of semantic knowledge reflecting brain pathophysiology that begins years before dementia. Identifying early signs of pathophysiology induced dysfunction in the neural systems that access and process words' meaning could therefore help forecast dementia. This article reviews pioneering studies demonstrating that abnormal functional Magnetic Resonance Imaging (fMRI) response patterns elicited in semantic tasks reflect both AD-pathophysiology and the hereditary risk of AD, and also can help forecast cognitive decline. However, to bring current semantic task-based fMRI research up to date with new AD research guidelines the relationship with different types of AD-pathophysiology needs to be more thoroughly examined. We shall argue that new analytic techniques and experimental paradigms will be critical for this. Previous work has relied on specialized tests of specific components of semantic knowledge/processing (e.g. famous name recognition) to reveal coarse AD-related changes in activation across broad brain regions. Recent computational advances now enable more detailed tests of the semantic information that is represented within brain regions during more natural language comprehension. These new methods stand to more directly index how pathophysiology alters neural information processing, whilst using language comprehension as the basis for a more comprehensive examination of semantic brain function. We here connect the semantic pattern information analysis literature up with AD research to raise awareness to potential cross-disciplinary research opportunities.

    View details for DOI 10.1016/j.nicl.2019.101788

    View details for Web of Science ID 000470123000004

    View details for PubMedID 30991624

    View details for PubMedCentralID PMC6451171

  • Longitudinal Functional Brain Mapping in Supernormals. Cerebral cortex (New York, N.Y. : 1991) Wang, X., Ren, P., Baran, T. M., Raizada, R. D., Mapstone, M., Lin, F. 2019; 29 (1): 242-252

    Abstract

    Prevention of age-related cognitive decline is an increasingly important topic. Recently, increased attention is being directed at understanding biological models of successful cognitive aging. Here, we examined resting-state brain regional low-frequency oscillations using functional magnetic resonance imaging in 19 older adults with excellent cognitive abilities (Supernormals), 28 older adults with normative cognition, 57 older adults with amnestic mild cognitive impairment, and 26 with Alzheimer's disease. We identified a "Supernormal map", a set of regions whose oscillations were resistant to the aging-associated neurodegenerative process, including the right fusiform gyrus, right middle frontal gyrus, right anterior cingulate cortex, left middle temporal gyrus, left precentral gyrus, and left orbitofrontal cortex. The map was unique to the Supernormals, differentiated this group from cognitive average-ager comparisons, and predicted a 1-year change in global cognition (indexed by the Montreal Cognitive Assessment scores, adjusted R2 = 0.68). The map was also correlated to Alzheimer's pathophysiological features (beta-amyloid/pTau ratio, adjusted R2 = 0.66) in participants with and without cognitive impairment. These findings in phenotypically successful cognitive agers suggest a divergent pattern of brain regions that may either reflect inherent neural integrity that contributes to Supernormals' cognitive success, or alternatively indicate adaptive reorganization to the demands of aging.

    View details for DOI 10.1093/cercor/bhx322

    View details for PubMedID 29186360

    View details for PubMedCentralID PMC6294410

  • Health Risk Prediction Models Incorporating Personality Data: Motivation, Challenges, and Illustration PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT Chapman, B. P., Lin, F., Roy, S., Benedict, R. B., Lyness, J. M. 2019; 10 (1): 46-58

    Abstract

    The age of "big data" in health has ushered in an era of prediction models promising to forecast individual health events. Although many models focus on enhancing the predictive power of medical risk factors with genomic data, a recent proposal is to augment traditional health predictors with psychosocial data, such as personality measures. In this article we provide a general overview of the medical risk prediction models and then discuss the rationale for integrating personality data. We suggest three principles that should guide work in this area if personality data is ultimately to be useful within risk prediction as it is actually practiced in the health care system. These include (a) prediction of specific, priority health outcomes; (b) sufficient incremental validity beyond established biomedical risk factors; and (c) technically responsible model-building that does not overfit the data. We then illustrate the application of these principles in the development of a personality-augmented prediction model for the occurrence of mild cognitive impairment, designed for a primary care setting. We evaluate the results, drawing conclusions for the direction an iterative, programmatic approach would need to take to eventually achieve clinical utility. Although there is great potential for personality measurement to play a key role in the coming era of risk prediction models, the final section reviews the many challenges that must be faced in real-world implementation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

    View details for DOI 10.1037/per0000300

    View details for Web of Science ID 000454703100006

    View details for PubMedID 30604983

    View details for PubMedCentralID PMC6319275

  • Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial TRIALS Yu, F., Lin, F., Salisbury, D. L., Shah, K. N., Chow, L., Vock, D., Nelson, N. W., Porsteinsson, A. P., Jack, C. 2018; 19: 700

    Abstract

    Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions.The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling.This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention.ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.

    View details for DOI 10.1186/s13063-018-3054-0

    View details for Web of Science ID 000454270500005

    View details for PubMedID 30577848

    View details for PubMedCentralID PMC6303946

  • A Systematic Review for Functional Neuroimaging Studies of Cognitive Reserve Across the Cognitive Aging Spectrum ARCHIVES OF CLINICAL NEUROPSYCHOLOGY Anthony, M., Lin, F. 2018; 33 (8): 937-948

    Abstract

    Cognitive reserve has been proposed to explain the discrepancy between clinical symptoms and the effects of aging or Alzheimer's pathology. Functional magnetic resonance imaging (fMRI) may help elucidate how neural reserve and compensation delay cognitive decline and identify brain regions associated with cognitive reserve. This systematic review evaluated neural correlates of cognitive reserve via fMRI (resting-state and task-related) studies across the cognitive aging spectrum (i.e., normal cognition, mild cognitive impairment, and Alzheimer's disease).This review examined published articles up to March 2017. There were 13 cross-sectional observational studies that met the inclusion criteria, including relevance to cognitive reserve, subjects 60 years or older with normal cognition, mild cognitive impairment, and/or Alzheimer's disease, at least one quantitative measure of cognitive reserve, and fMRI as the imaging modality. Quality assessment of included studies was conducted using the Newcastle-Ottawa Scale adapted for cross-sectional studies.Across the cognitive aging spectrum, medial temporal regions and an anterior or posterior cingulate cortex-seeded default mode network were associated with neural reserve. Frontal regions and the dorsal attentional network were related to neural compensation. Compared to neural reserve, neural compensation was more common in mild cognitive impairment and Alzheimer's disease.Neural reserve and compensation both support cognitive reserve, with compensation more common in later stages of the cognitive aging spectrum. Longitudinal and intervention studies are needed to investigate changes between neural reserve and compensation during the transition between clinical stages, and to explore the causal relationship between cognitive reserve and potential neural substrates.

    View details for DOI 10.1093/arclin/acx125

    View details for Web of Science ID 000455329500001

    View details for PubMedID 29244054

    View details for PubMedCentralID PMC6246379

  • Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES Victoroff, J., Lin, F. V., Coburn, K. L., Shillcutt, S. D., Voon, V., Ducharme, S. 2018; 30 (1): 14-21

    Abstract

    Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.

    View details for DOI 10.1176/appi.neuropsych.16080155

    View details for Web of Science ID 000437978600004

    View details for PubMedID 28876969

  • The impact of a positive cognitive impairment screen on conversations between patients, caregivers, and oncologists: A UR NCORP randomized study. Magnuson, A., Lei, L., Janelsins, M., Culakova, E., Lin, F., Gilles, M., Hurria, A., Dale, W., Duberstein, P., Wittink, M., Wells, M., Gilmore, N., Hamel, L. M., O'Rourke, M., Onitilo, A. A., Bradley, T., Whitehead, M., Mohile, S. AMER SOC CLINICAL ONCOLOGY. 2018
  • Geriatric assessment with management intervention in older adults with cancer: a randomized pilot study SUPPORTIVE CARE IN CANCER Magnuson, A., Lemelman, T., Pandya, C., Goodman, M., Noel, M., Tejani, M., Doughtery, D., Dale, W., Hurria, A., Janelsins, M., Lin, F., Heckler, C., Mohile, S. 2018; 26 (2): 605–13

    Abstract

    Older adults receiving cancer therapy have heightened risk for treatment-related toxicity. Geriatric assessment (GA) can identify impairments, which may contribute to vulnerability and adverse outcomes. GA management interventions can address these impairments and have the potential to improve outcomes when implemented.We conducted a randomized pilot study comparing GA with management interventions versus usual care in patients with stage III/IV solid tumor malignancies (N = 71). In all patients, a trained coordinator conducted and scored a baseline GA with pre-determined cutoffs for impairment. For patients randomized to the intervention arm, an algorithm was used to identify GA management recommendations based upon identified impairments. Recommendations were relayed to the primary oncologist for implementation. GA was repeated at 3 months. The primary outcome was grade 3-5 chemotherapy toxicity. Secondary outcomes included feasibility, hospitalizations, dose reductions, dose delays, and early treatment discontinuation.The mean participant age was 76 (70-89). The total number of GA management recommendations relayed was 409, of which 35.4% were implemented by the primary oncologist. Incidence of grade 3-5 chemotherapy toxicity did not differ between the two groups. Prevalence of hospitalization, dose reductions, dose delays, and early treatment discontinuation also did not differ between the two groups.An algorithm can be used to guide GA management recommendations in older adults with cancer. However, reliance upon the primary oncologist for execution resulted in a low prevalence of implementation. Future work should aim to understand barriers to implementation and explore alternate models of implementing geriatric-focused care for older adults with cancer.

    View details for PubMedID 28914366

    View details for PubMedCentralID PMC5887127

  • Apolipoprotein E genotype impact on memory and attention in older persons: the moderating role of personality phenotype INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Chapman, B. P., Benedict, R. B., Lin, F., Roy, S., Porteinsson, A., Szigeti, K., Federoff, H., Mapstone, M. 2018; 33 (2): 332-339

    Abstract

    To determine if phenotypic personality traits modify the association of Apolipoprotein E (APOE) genotypes with different domains of cognitive function.Cross-sectional.172 non-demented older adults were administered the NEO-Five Factor Inventory (NEO-FFI), a battery of neuropsychological tests assessing memory, attention, executive function, language, and visuospatial ability, and underwent APOE genotyping. Multivariate (multiple-dependent variable) regression models predicting cognitive domains tested APOE interactions with personality traits, adjusting for age, sex, and education.The APOE ε4 allele showed small to modest main effects on memory and executive function (1/3 SD deficits for carriers, p < .05), with ε2 status evidencing minimal and non-significant benefit. Neuroticism interacted with both ε2 and ε4 alleles in associations with attention scores (p = .001), with ε2 benefits and ε4 deficits being marked at high Neuroticism (Mean [M] covariate-adjusted Z-score = .39 for ε2, -.47 for ε4). The association of ε4 with memory was moderated by Conscientiousness (p < .001), such that ε4 memory deficits were apparent at low Conscientiousness (M = -.56), but absent at high levels of Conscientiousness. Weaker patterns (p < .05) also suggested ε4-related detriments in executive function only at lower Conscientiousness, and ε2 memory benefits only at higher Openness.Conscientiousness and Neuroticism moderate APOE associations with memory and executive function. As such, they may be useful phenotypic markers in refining the prognostic significance of this polymorphism. Effect-modifying personality traits also provide clues about behavioral and psychological factors that influence the cognitive impact of APOE. Copyright © 2017 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/gps.4748

    View details for Web of Science ID 000422754300033

    View details for PubMedID 28612377

  • Amyloid and FDG PET of Successful Cognitive Aging: Global and Cingulate-Specific Differences JOURNAL OF ALZHEIMERS DISEASE Baran, T. M., Lin, F. 2018; 66 (1): 307-318

    Abstract

    Some individuals, called Supernormals (SN), maintain excellent memory in old age. While brain structural and functional integrity in SN seem to be aging-resistant, their amyloidosis and neural injury status has not been well studied.The goal of this study was to compare cortical amyloid deposition and glucose metabolism between SN and older adults with normal cognition (NC), amnestic mild cognitive impairment (MCI), and Alzheimer's disease (AD).Subjects from the ADNI database were included if they received T1-weighted MRI, amyloid PET, FDG-PET, and cognitive testing within a 6-month period, yielding 27 AD, 69 MCI, 172 NC, and 122 SN. PET standardized uptake value ratios (SUVrs) were calculated for the whole cortex and 68 regions of interest, with whole cerebellum serving as reference.SN had lower whole cortex amyloid than MCI, and higher glucose metabolism than all others. Regional analysis revealed that amyloid burden and glucose metabolism in the right isthmus cingulate cortex differed in SN compared to others, while SN glucose metabolism also differed from others in several frontal and temporal regions.Preserved cortical glucose metabolism, and lower levels of amyloidosis and glucose hypometabolism in the right isthmus cingulate cortex, contributes to the Supernormal phenomenon. These findings may be informative for development of early screening biomarkers and therapeutic targets for modification of cognitive trajectories.

    View details for DOI 10.3233/JAD-180360

    View details for Web of Science ID 000448213400020

    View details for PubMedID 30282358

    View details for PubMedCentralID PMC6538036

  • Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment NEUROIMAGE-CLINICAL Ren, P., Chapman, B., Zhang, Z., Schifitto, G., Lin, F. 2018; 20: 297-304

    Abstract

    Locus of control (LOC) is an important personality trait. LOC over cognitive competency reflects an individual's perceived control of desired cognitive outcomes, which is critical for maintaining successful cognitive aging. It is important to understand the neural substrates of LOC over cognitive competency in older adults, especially for individuals at high risk of dementia. Here, we characterized a cohesive functional and structural connectivity profile underlying LOC among 55 older adults with amnestic mild cognitive impairment (aMCI), combining resting-state functional magnetic resonance imaging and diffusion tensor imaging. The results showed that both functional and structural connectivity between the medial prefrontal cortex and amygdala were significantly correlated with external LOC. The functional connectivity mediated the correlation between structural connectivity and external LOC. In addition, aging-associated neurodegeneration moderated the relationship between structural connectivity and external LOC, showing that the structural connectivity was positively correlated with external LOC in low, but not high neurodegeneration. Our results suggest a critical role of the functional amygdala-frontal network, which may serve as a bridge between its white matter tract and LOC over cognitive competency in groups at high risk for dementia.

    View details for DOI 10.1016/j.nicl.2018.07.021

    View details for Web of Science ID 000450799000033

    View details for PubMedID 30101061

    View details for PubMedCentralID PMC6083450

  • Cortical thickness is associated with altered autonomic function in cognitively impaired and non-impaired older adults JOURNAL OF PHYSIOLOGY-LONDON Lin, F., Ren, P., Wang, X., Anthony, M., Tadin, D., Heffner, K. L. 2017; 595 (22): 6969-6978

    Abstract

    The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. Alzheimer's disease (AD), via frontal compensatory processes, may affect PNS regulation, thereby compromising older adults' capacity for adaptation, and increasing morbidity and mortality risk. Here we found that AD-associated neurodegeneration accompanied an overactive anterior cingulate cortex, which in turn resulted in a high level of PNS activity at rest, as well as strong PNS activity withdrawal in response to the mental effort. This discovery provides the first line of evidence to suggest that AD-associated neurodegeneration links to altered PNS regulation during mental effort in older adults, and that the compensatory processes accompanying frontal hyperactivation appear to be responsible for these alterations.The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. PNS can reflect an individual's regulatory capacity of frontal brain regions and has been linked to cognitive capacity. Yet, the relationship of PNS function to cognitive decline and abnormal frontal function that characterize preclinical progression toward Alzheimer's disease (AD) is unclear. Here, we aimed to elucidate the relationship between PNS function and AD-associated neurodegeneration by testing two competing hypotheses involving frontal regions' activity (neurodegeneration vs. compensation). In 38 older human adults with amnestic mild cognitive impairment (aMCI) or normative cognition, we measured AD-associated neurodegeneration (AD signature cortical thickness; ADSCT), resting-state functional magnetic resonance imaging of frontal regions' spontaneous activation, and an electrocardiography measure of PNS (high frequency heart rate variability; HF-HRV). HF-HRV was assessed at rest and during a cognitive task protocol designed to capture HF-HRV reactivity. Higher HF-HRV at rest was significantly related to both more severe AD-associated neurodegeneration (lower ADSCT scores) and worse cognitive ability. Cognitive impairments were also related to greater suppression of HF-HRV reactivity. High activities of the anterior cingulate cortex significantly mediated relationships between ADSCT and both HF-HRV at rest and HF-HRV reactivity. Notably, these relationships were not affected by the clinical phenotype. We show that AD-associated neurodegeneration is associated with altered PNS regulation and that compensatory processes linked to frontal overactivation might be responsible for those alterations. This finding provides the first line of evidence in a new framework for understanding how early-stage AD-associated neurodegeneration affects autonomic regulation.

    View details for DOI 10.1113/JP274714

    View details for Web of Science ID 000417113000023

    View details for PubMedID 28952161

    View details for PubMedCentralID PMC5685832

  • Acute Affective Reactivity and Quality of Life in Older Adults with Amnestic Mild Cognitive Impairment: A Functional MRI Study AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Ren, P., Heffner, K. L., Jacobs, A., Lin, F. 2017; 25 (11): 1225-1233

    Abstract

    Poor quality of life (QoL) is a major concern among older adults with amnestic mild cognitive impairment (MCI). Maladaptive affective regulation and its relevant frontal dysfunction that are often observed in older adults with MCI may provide an insight into the understanding of their QoL.In this case-controlled study, participants (MCI patients, N = 18; healthy comparisons [HC], N = 21) completed cognitive tasks, and underwent resting-state functional magnetic resonance imaging (rs-fMRI) immediately before and after the tasks. The amplitude of low-frequency fluctuations (ALFF) of rs-fMRI signals was calculated to examine the brain's spontaneous activity. The change in valence from the Self-Assessment Manikin indexed affective reactivity. QoL was assessed using Quality of Life-AD measure. Multiple mediator model was used to examine the mediating effect of frontal regions' ALFF reactivity between the affective reactivity and QoL.The MCI group had significantly worse QoL and more negative affective reactivity than HC group. Less negative affective reactivity was significantly associated with better QoL in MCI not HC. ALFF in the anterior cingulate cortex, medial prefrontal cortex (MPFC), and superior frontal gyrus (SFG) increased significantly less after cognitive tasks in MCI than HC. For the entire sample, greater increases of ALFF in MPFC and SFG were significantly associated with better QoL, and SFG alone significantly mediated the association between affective reactivity and QoL.Enhancing SFG activation, especially among those with MCI, may provide a therapeutic target for addressing the negative impact of maladaptive affective regulation on QoL.

    View details for DOI 10.1016/j.jagp.2017.06.019

    View details for Web of Science ID 000413330200011

    View details for PubMedID 28755988

    View details for PubMedCentralID PMC5654660

  • Personality and Performance in Specific Neurocognitive Domains Among Older Persons AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Chapman, B. P., Benedict, R. H., Lin, F., Roy, S., Federoff, H. J., Mapstone, M. 2017; 25 (8): 900-908

    Abstract

    Certain Big 5 personality dimensions have been repeatedly linked to global measures of cognitive function and outcome categories. We examined whether the Big 5 or their specific components showed differential evidence of associations with specific neurocognitive domains.Participants were 179 older adults (70+) from a broader study on cognitive aging. The NEO-Five Factor Inventory and a comprehensive battery of neuropsychological tests were used.Adjusted for age, gender, and years of education, probability values, Bayes Factors, and measures effect size from linear models suggested strong evidence for associations between better delayed recall memory and higher Conscientiousness (principally the facets of Goal-Striving and Dependability) and Openness (specifically the Intellectual Interest component). Better executive function and attention showed moderate to strong evidence of associations with lower Neuroticism (especially the Self-conscious Vulnerability facet) and higher Conscientiousness (mostly the Dependability facet). Better language functioning was linked to higher Openness (specifically, the Intellectual Interests facet). Worse visual-spatial function was strongly associated with higher Neuroticism.Different tests of neurocognitive functioning show varying degrees of evidence for associations with different personality traits. Better understanding of the patterning of neurocognitive-personality linkages may facilitate grasp of underlying mechanisms and/or refine understanding of co-occurring clinical presentation of personality traits and specific cognitive deficits.

    View details for DOI 10.1016/j.jagp.2017.03.006

    View details for Web of Science ID 000410622900011

    View details for PubMedID 28456386

    View details for PubMedCentralID PMC5647872

  • Amygdala functional connectivity is associated with locus of control in the context of cognitive aging NEUROPSYCHOLOGIA Ren, P., Anthony, M., Chapman, B. P., Heffner, K., Lin, F. 2017; 99: 199-206

    Abstract

    Locus of control (LOC) measures the extent to which individuals perceive control over their lives. Those with a more "internal" LOC feel self-sufficient and able to determine important aspects of their own future, while those with a more "external" LOC feel that their lives are governed by events beyond their control. Reduced internal LOC and increased external LOC have been found in cognitive disorders, but the neural substrates of these control perceptions are yet unknown. In the present study, we explored the relationship between amygdala functional connectivity and LOC in 18 amnestic mild cognitive impairment (MCI) and age-, sex-, and education-matched, 22 cognitively healthy controls (HC). Participants completed cognitive challenge tasks (Stroop Word Color task and Dual 1-back) for 20min, and underwent resting-state functional magnetic resonance imaging immediately before and after the tasks. We found significantly lower internal LOC and higher external LOC in the MCI group than the HC group. Compared to HC, MCI group showed significantly stronger positive associations between internal LOC and baseline right amygdala connections (including right middle frontal gyrus and anterior cingulate cortex), and stronger negative associations between internal LOC and change of these right amygdala connections. Across all participants, external LOC explained the relationships between associations of another set of right amygdala connections (including middle cingulate cortex and right superior frontal gyrus), both at baseline and for change, and performance in the cognitive challenge tasks. Our findings indicate that the right amygdala networks might be critical in understanding the neural mechanisms underlying LOC's role in cognitive aging.

    View details for DOI 10.1016/j.neuropsychologia.2017.03.016

    View details for Web of Science ID 000401202600021

    View details for PubMedID 28315366

    View details for PubMedCentralID PMC5404937

  • What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessons for Alzheimer ' s disease NEUROBIOLOGY OF AGING Mapstone, M., Lin, F., Nalls, M. A., Cheema, A. K., Singleton, A. B., Fiandaca, M. S., Federoff, H. J. 2017; 51: 148-155

    Abstract

    As the world population ages, primary prevention of age-related cognitive decline and disability will become increasingly important. Prevention strategies are often developed from an understanding of disease pathobiology, but models of biological success may provide additional useful insights. Here, we studied 224 older adults, some with superior memory performance (n = 41), some with normal memory performance (n = 109), and some with mild cognitive impairment or Alzheimer's disease (AD; n = 74) to understand metabolomic differences which might inform future interventions to promote cognitive health. Plasma metabolomics revealed significant differential abundance of 12 metabolites in those with superior memory relative to controls (receiver operating characteristic area under the curve [AUC] = 0.89) and the inverse abundance pattern in the mild cognitive impairment, AD (AUC = 1.0) and even preclinical AD groups relative to controls (AUC = 0.97). The 12 metabolites are components of key metabolic pathways regulating oxidative stress, inflammation, and nitric oxide bioavailability. These findings from opposite ends of the cognitive continuum highlight the role of these pathways in superior memory abilities and whose failure may contribute to age-related memory impairment. These pathways may be targeted to promote successful cognitive aging.

    View details for DOI 10.1016/j.neurobiolaging.2016.11.007

    View details for Web of Science ID 000397168600016

    View details for PubMedID 27939698

    View details for PubMedCentralID PMC5985530

  • Activity engagement and physical function in old age sample ARCHIVES OF GERONTOLOGY AND GERIATRICS Shah, K. N., Lin, F. V., Yu, F., McMahon, J. M. 2017; 69: 55-60

    Abstract

    To describe the patterns of engagement in mental, physical, and social activity (MA, PA, and SA) and to examine the relationship between combined activity engagement and physical function among community-dwelling older adults.Cross-sectional correlational study.Multiple communities.A total of 466 individuals aged 55 years or older.Physical function was assessed using grip strength and gait speed. Engagement in PA, MA and SA was obtained from self-report questionnaires.We identified four classes ("Active PA and MA", "Active MA", "Active PA", and "Inactive") that significantly differed in the frequency of engagement in MA and PA using latent class analysis. SA didn't differ across classes. Controlling for age, the "Active PA and MA", "Active MA", "Active PA" groups displayed similar grip strength that was superior to the "Inactive" group. "Active PA and MA" group had best gait speed relative to other groups, especially "Active MA" and "Inactive" group, while the "Active PA", "Active MA", and "Inactive" group were similar in gait speed.Combined physical and mental activity engagement was associated with better physical function, especially in gait speed. Future interventional research should investigate the combination of both physical and cognitive training to prevent decline of physical function in older adults.

    View details for DOI 10.1016/j.archger.2016.11.007

    View details for Web of Science ID 000390449000008

    View details for PubMedID 27888736

    View details for PubMedCentralID PMC5217742

  • Identification of Successful Cognitive Aging in the Alzheimer's Disease Neuroimaging Initiative Study JOURNAL OF ALZHEIMERS DISEASE Lin, F. V., Wang, X., Wu, R., Rebok, G. W., Chapman, B. P., Alzheimer's Dis Neuroimaging 2017; 59 (1): 101-111

    Abstract

    The present prospective observational study aimed to identify the existence of successful cognitive agers among a group of well-defined cognitively healthy older adults (n = 354, mean age = 75 years), and to examine baseline individual-level predictors and associated health outcomes over time. Episodic memory (EM) and executive function (EF) composite scores and multiple health outcomes were obtained annually over 5 years. Potential individual-level predictors that were related to Alzheimer's disease pathology or genetic risk, neurodegeneration, and vascular risks were collected at baseline. Three latent classes with matched age and education were identified using growth mixture modeling: a group of participants who exhibited high, stable EM and EF (40.7% of the sample, "successful agers"); a group who had initial high cognitive performance that declined over time (21.2%, "declining agers"); and a group who had normal (EM) or poor (EF) but stable cognitive performance over time (38.1%, "low stable agers"). The group classification predicted significant differences in the incidence of global cognitive impairment, the development of at least one depressive symptom, and everyday functional impairment. Sex, apolipoprotein E allele 4, amyloid-β1-42, and t-tau significantly contributed to the difference in cognitive trajectories between the successful agers and the other two groups. Characterizing successful cognitive agers who are relatively resistant to both tau and amyloid pathology provides potential pathways for promoting successful cognitive aging and preventing cognitive decline.

    View details for DOI 10.3233/JAD-161278

    View details for Web of Science ID 000404876400011

    View details for PubMedID 28582857

    View details for PubMedCentralID PMC5661994

  • Insula and Inferior Frontal Gyrus' Activities Protect Memory Performance Against Alzheimer's Disease Pathology in Old Age JOURNAL OF ALZHEIMERS DISEASE Lin, F., Ren, P., Lo, R. Y., Chapman, B. P., Jacobs, A., Baran, T. M., Porsteinsson, A. P., Foxe, J. J., Alzheimers Dis Neuroimaging Initia 2017; 55 (2): 669-678

    Abstract

    Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid- β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEɛ4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEɛ4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics.

    View details for DOI 10.3233/JAD-160715

    View details for Web of Science ID 000389695700020

    View details for PubMedID 27716674

    View details for PubMedCentralID PMC5531269

  • The cingulate cortex of older adults with excellent memory capacity CORTEX Lin, F., Ren, P., Mapstone, M., Meyers, S. P., Porsteinsson, A., Baran, T. M., Alzheimer's Dis Neuroimaging Initi 2017; 86: 83-92

    Abstract

    Memory deterioration is the earliest and most devastating cognitive deficit in normal aging and Alzheimer's disease (AD). Some older adults, known as "Supernormals", maintain excellent memory. This study examined relationships between cerebral amyloid deposition and functional connectivity (FC) within the cingulate cortex (CC) and between CC and other regions involved in memory maintenance between Supernormals, healthy controls (HC), and those at risk for AD (amnestic mild cognitive impairment [MCI]). Supernormals had significantly stronger FC between anterior CC and R-hippocampus, middle CC (MCC) and L-superior temporal gyrus, and posterior CC (PCC) and R-precuneus, while weaker FC between MCC and R-middle frontal gyrus and MCC and R-thalamus than other groups. All of these FC were significantly related to memory and global cognition in all participants. Supernormals had less amyloid deposition than other groups. Relationships between global cognition and FC were stronger among amyloid positive participants. Relationships between memory and FC remained regardless of amyloid level. This revealed how CC-related neural function participates in cognitive maintenance in the presence of amyloid deposition, potentially explaining excellent cognitive function among Supernormals.

    View details for DOI 10.1016/j.cortex.2016.11.009

    View details for Web of Science ID 000393929000008

    View details for PubMedID 27930899

    View details for PubMedCentralID PMC5253250

  • A Role of the Parasympathetic Nervous System in Cognitive Training CURRENT ALZHEIMER RESEARCH Lin, F., Heffner, K. L., Ren, P., Tadin, D. 2017; 14 (7): 784-789

    Abstract

    Vision-based speed of processing (VSOP) training can result in broad cognitive improvements in older adults with amnestic mild cognitive impairment (aMCI). What remains unknown, however, is what neurophysiological mechanisms account for the observed training effect. Much of the work in this area has focused on the central nervous system, neglecting the fact that the peripheral system can contributes to changes of the central nervous system and vice versa.We examined the prospective relationship between an adaptive parasympathetic nervous system response to cognitive stimuli and VSOP training-induced plasticity.Twenty-one participants with aMCI (10 for VSOP training, and 11 for mental leisure activities (MLA) control) were enrolled. We assessed high-frequency heart rate variability (HF-HRV) during training sessions, and striatum-related neural networks and cognition at baseline and post-training.Compared to MLA, the VSOP group showed a significant U-shaped pattern of HF-HRV response during training, as well as decreases in connectivity strength between bilateral striatal and prefrontal regions. These two effects were associated with training-induced improvements in both the trained (attention and processing speed) and transferred (working memory) cognitive domains.This work provides novel support for interactions between the central and the peripheral nervous systems in relation to cognitive training, and motivates further studies to elucidate the causality of the observed link.

    View details for DOI 10.2174/1567205014666170203095128

    View details for Web of Science ID 000403945700010

    View details for PubMedID 28164771

    View details for PubMedCentralID PMC5530077

  • ACTIVITY OF INSULAR AND INFERIOR FRONTAL GYRUS PROTECT MEMORY AGAINST ALZHEIMER'S PATHOLOGY Lin, F., Ren, P., Lo, R., Chapman, B., Jacobs, A., Baran, T., Porsteinsson, A. OXFORD UNIV PRESS INC. 2016: 535-536
  • CRITICAL GERONTOLOGY AND LIFE COURSE PERSPECTIVES A NEW FRAMEWORK FOR UNDERSTANDING LIFESPAN COGNITIVE DEVELOPMENT Wu, R., Hannagan, T., Rebok, G., Lin, F. OXFORD UNIV PRESS INC. 2016: 224
  • LONGITUDINAL FUNCTIONAL DECLINE OF THE STRIATUM IN MILD COGNITIVE IMPAIRMENT Ren, P., Lo, R., Chapman, B., Mapstone, M., Porsteinsson, A., Lin, F. OXFORD UNIV PRESS INC. 2016: 535
  • Cognitive and Neural Effects of Vision-Based Speed-of-Processing Training in Older Adults with Amnestic Mild Cognitive Impairment: A Pilot Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Lin, F., Heffner, K. L., Ren, P., Tivarus, M. E., Brasch, J., Chen, D., Mapstone, M., Porsteinsson, A. P., Tadin, D. 2016; 64 (6): 1293-1298

    Abstract

    To examine the cognitive and neural effects of vision-based speed-of-processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).Randomized single-blind controlled pilot trial.Academic medical center.Individuals with aMCI (N = 21).Six-week computerized VSOP training.Multiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).VSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19  = 6.61, partial η(2)  = 0.26, P = .02) and untrained (working memory: F1,19  = 7.33, partial η(2)  = 0.28, P = .01; IADLs: F1,19  = 5.16, partial η(2)  = 0.21, P = .03) cognitive domains than MLA and protective maintenance in DMN (F1, 9  = 14.63, partial η(2)  = 0.62, P = .004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = -2.37, P = .02).Target and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.

    View details for DOI 10.1111/jgs.14132

    View details for Web of Science ID 000383546900018

    View details for PubMedID 27321608

    View details for PubMedCentralID PMC4916855

  • Mental Fatigability and Heart Rate Variability in Mild Cognitive Impairment AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Lin, F., Ren, P., Cotton, K., Porsteinsson, A., Mapstone, M., Heffner, K. L. 2016; 24 (5): 374-378

    Abstract

    Adaptive physiological stress regulation is rarely studied in mild cognitive impairment (MCI). Here we targeted mental fatigability (MF) as a determinant of altered high frequency heart rate variability (HF-HRV) reactivity in individuals with MCI, and examined frontobasal ganglia circuitry as a neural basis supporting the link between MF and HF-HRV reactivity.We measured mental fatigability and HF-HRV during a 60-minute cognitive stress protocol in 19 individuals with MCI. HF-HRV responses were modeled using a quadratic equation. Resting state functional connectivity of intra- and inter-network frontobasal ganglia circuitry was assessed using blood-oxygen-level-dependent magnetic resonance imaging among seven of the participants.Lower MF was associated with faster and greater rebound in U-shape HF-HRV reactivity, which linked to a stronger connectivity between right middle frontal gyrus and left putamen.Results suggest that MF may contribute to abnormal physiological stress regulation in MCI, and fronto basal ganglia circuitry may support the link.

    View details for DOI 10.1016/j.jagp.2015.12.012

    View details for Web of Science ID 000375054800006

    View details for PubMedID 26905050

    View details for PubMedCentralID PMC4846469

  • Trajectories of Neuropsychiatric Symptoms and Cognitive Decline in Mild Cognitive Impairment David, N., Lin, F., Porsteinsson, A. P. ELSEVIER SCIENCE INC. 2016: S113-S115
  • A Novel Theoretical Life Course Framework for Triggering Cognitive Development across the Lifespan HUMAN DEVELOPMENT Wu, R., Rebok, G. W., Lin, F. 2016; 59 (6): 342-365

    View details for DOI 10.1159/000458720

    View details for Web of Science ID 000400220600002

  • Trajectories of Neuropsychiatric Symptoms and Cognitive Decline in Mild Cognitive Impairment AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY David, N. D., Lin, F., Porsteinsson, A. P., Alzheimers Dis Neuroimaging Initia 2016; 24 (1): 70-80

    Abstract

    To characterize the course of neuropsychiatric symptoms (NPS) in adults with mild cognitive impairment (MCI), and to examine baseline individual-level predictors and associated cognitive and functional outcomes.A 2-year prospective cohort study.Multicenter clinical settings.Five hundred sixty individuals with MCI at baseline.NPS severity (measured using Neuropsychiatric Inventory Questionnaire) and cognitive and functional outcomes were assessed at baseline and every 6 months thereafter. Potential individual-level predictors were collected at baseline.Three latent classes of NPS courses were identified using growth mixture modeling: a stable class in which a low NPS burden remained relatively unchanged over time (N = 503, 89.8%); a worsened class in which an initially moderate NPS burden increased (N = 39, 7.0%); and an improved class in which an initially high NPS burden decreased (N = 18, 3.2%). There were no associations between class membership and baseline individual characteristics. Members of the worsened class were 1.74 times more likely to be diagnosed with incident Alzheimer disease (AD) than members of the stable class (95% confidence interval: 1.07-2.84). The worsened class also showed significantly more rapid declines in cognitive and functional outcomes than the stable class. Class membership did not predict rate of brain atrophy.Patients with MCI may experience different trajectories of NPS over time. Patients with worsening NPS may be at greater risk of developing AD and severe cognitive and functional impairment.

    View details for DOI 10.1016/j.jagp.2015.06.001

    View details for Web of Science ID 000367334400010

    View details for PubMedID 26525995

    View details for PubMedCentralID PMC4691566

  • Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment JOURNAL OF ALZHEIMERS DISEASE Ren, P., Lo, R. Y., Chapman, B. P., Mapstone, M., Porsteinsson, A., Lin, F., Alzheimer's Dis Neuroimaging Initi 2016; 54 (1): 69-78

    Abstract

    The striatum is a critical functional hub in understanding neurological disorders. However, the Alzheimer's disease (AD)-associated striatal change is unclear, as is the relationship between striatal change and AD pathology. Three-year resting-state fMRI data from 15 healthy control (HC) and 20 mild cognitive impairment (MCI) participants were obtained. We analyzed the amplitude of low-frequency fluctuations (ALFF) (0.01-0.08 Hz) and two subdivided bands (slow-4:0.027-0.073 Hz; slow-5:0.01-0.027 Hz). We calculated Aβ/pTau ratio using baseline cerebrospinal fluid pTau and Aβ1-42 to represent AD pathology. Compared to HC, MCI participants showed greater decline in right putaminal ALFF, including the slow-4 band. Greater decline of ALFF in the right putamen was significantly related to the memory decline over time and lower baseline Aβ/pTau ratio regardless of age or group. The slow-4 band, relative to slow-5 band, showed a stronger correlation between Aβ/pTau ratio and decline of ALFF in the right putamen. The results suggest that the putaminal function declines early in the AD-associated neurodegeneration. The continuous decline in putaminal ALFF, especially slow-4 band, may be a sensitive marker of AD pathology such as Aβ/pTau ratio regardless of clinical diagnosis.

    View details for DOI 10.3233/JAD-160368

    View details for Web of Science ID 000383838400006

    View details for PubMedID 27472880

    View details for PubMedCentralID PMC5003682

  • Distraction from Novel Information vs. Existing Knowledge in Aging Adults Wu, R., Lin, F. OXFORD UNIV PRESS INC. 2015
  • Mechanisms Linking Depression and Cognitive Impairment: A Systematic Review of Neuroimaging Studies Cotton, K., Jacobs, A., Ren, P., Lin, F. OXFORD UNIV PRESS INC. 2015
  • Stress regulation as a link between executive function and pre-frailty in older adults JOURNAL OF NUTRITION HEALTH & AGING Roiland, R. A., Lin, F., Phelan, C., Chapman, B. P. 2015; 19 (8): 828-838

    Abstract

    Both pre-frailty and frailty are linked with impaired executive function (EF) but the mechanism underlying this relationship is not known. Williams and colleagues' model posits EF affects health outcomes via stress regulation. This model was utlized to test indicators of stress regulation as mediators of the relationship between EF and pre-frailty in older adults.Cross-sectional.Academic general clinical research centers.690 community-dwelling older adults ≥ 50 years of age.Pre-frailty was measured using a modified form of the Fried Frailty measure. EF was assessed via telephone-based neurocognitive assessments. Indicators of stress regulation included: stress exposure (measured by perceived stress), reactivity and recovery (measured by heart rate) and restoration (measured by serum interleukin-6 and sleep quality).396 individuals were classified as non-frail, 277 as pre-frail, and 17 as frail. Pre-frail and non-frail individuals were included in data analyses. Compared to non-frail individuals, pre-frail were older and exhibited poorer EF, higher levels of stress exposure and poorer stress restoration. Poorer EF was associated with greater stress exposure, less stress reactivity, longer stress recovery and poorer stress restoration. The total effect of the relationship between EF and pre-frailty was significant with significant indirect effects supporting stress exposure and restoration as mediators of the relationship.Stress exposure and restoration appear to mediate the relationship between EF and pre-frailty. Longitudinal studies are needed to clarify the direction of causality and determine whether stress regulation processes are appropriate targets for interventions aiming to prevent declines in EF and the development of pre-frailty.

    View details for DOI 10.1007/s12603-015-0476-1

    View details for Web of Science ID 000362683900005

    View details for PubMedID 26412287

    View details for PubMedCentralID PMC5267317

  • Feasibility study of an attention training application for older adults INTERNATIONAL JOURNAL OF OLDER PEOPLE NURSING Hill, N. L., Mogle, J., Colancecco, E., Dick, R., Hannan, J., Lin, F. 2015; 10 (3): 241-249

    Abstract

    Technology-based attention training has demonstrated promise in its potential to improve cognitive functioning in older people. Developing mobile applications, with older users specifically in mind, may support future dissemination of these interventions and integration into daily life.The purpose of this pilot study was to test the feasibility of an Attention Training Application (ATA) for community-dwelling older adults using mobile technology.A descriptive, mixed-methods design was used to capture older adults' feedback on the usability and acceptability of the ATA.A convenience sample of older adults (n = 9) from two independent living facilities participated in a 2-hour training and practice session with the ATA. Participants were given personally tailored instructions for using the mobile device and the ATA specifically. Following a practice session, participants provided ratings on multiple components of the ATA and completed an audio-recorded, semi-structured interview to provide detailed descriptions of their experience and perceptions. An iterative process of content analysis was used to characterise the open-ended responses.Participants rated the ATA favourably overall on several 0-10 scales including likeability [8.5 (1.6)], interest [8.8 (2.3)] and satisfaction [8.2 (1.9)]. The qualitative analyses revealed several issues relevant to the feasibility of the ATA among older people including the importance of the technological background of the user, limiting negative feedback, challenges with the touch screen interface, personal preferences for challenge, extending the practice period and the difficulty of the dual-task condition.The use of the ATA is feasible in the older adult population. Future development should specifically consider personal characteristics as well as preferences to maximise usability and acceptability among older people.Older adults enjoyed the ATA. This opens doors to user-friendly technological interventions that may be effective in assisting older adults maintain and possibly even improve their cognitive function.

    View details for DOI 10.1111/opn.12092

    View details for Web of Science ID 000359834100010

    View details for PubMedID 26073545

  • The Moderating Effect of Personality Type on the Relationship Between Leisure Activity and Executive Control in Older Adults ACTIVITIES ADAPTATION & AGING Hill, N. L., Lin, F., Parisi, J. M., Kolanowski, A. 2015; 39 (2): 153-176

    Abstract

    We examined the moderating effect of personality on the association between leisure activities and executive control in healthy community-dwelling older adults. We found two distinct personality typologies: individuals with a Resilient personality were characterized by emotional stability and self-confidence; whereas, those who resembled an Overcontrolled personality tended to be introverted, but also low on neuroticism. Resilient individuals were more likely than Overcontrolled individuals to demonstrate higher executive function and attention as a result of participation in mental activities. These results suggest that personality might be important to include in studies that test the efficacy of activity interventions for improving cognition.

    View details for DOI 10.1080/01924788.2015.1025659

    View details for Web of Science ID 000211921000004

    View details for PubMedID 27087715

    View details for PubMedCentralID PMC4833400

  • Linking cognition and frailty in middle and old age: metabolic syndrome matters INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Lin, F., Roiland, R., Chen, D., Qiu, C. 2015; 30 (1): 64-71

    Abstract

    This study examined whether metabolic syndrome (MetS) would moderate the association of cognition with frailty in middle and old age.A cross-sectional design was used. Six hundred and ninety participants (age ≥ 50 years) from an on-going national survey were included in the study. Confirmatory factor analysis was applied to determine latent variables of executive function (EF), episodic memory (EM), and MetS based on relevant measurements. Frailty was defined using a modified form of Fried's criteria.Applying structural equation modeling, having MetS significantly increased the likelihood of being frail. Better performance on EM tasks, but not EF, was significantly associated with lower likelihood of MetS. Worse performance on EF, but not EM, significantly increased the likelihood of being frail. There was a significant interacting effect between MetS and EF, but not EM, on frailty. Further contrast analysis indicated that having MetS strengthened the negative association between EF and frailty.Metabolic syndrome moderates the relationship between EF and frailty. A prospecitve study is needed to validate such relationships before developing interventions targeting the prevention or treatment of EF and frailty in individuals with MetS.

    View details for DOI 10.1002/gps.4115

    View details for Web of Science ID 000346278300007

    View details for PubMedID 24733716

    View details for PubMedCentralID PMC4198518

  • Cusp Catastrophe Polynomial Model: Power and Sample Size Estimation. Open journal of statistics Chen, D. D., Chen, X. J., Lin, F., Tang, W., Lio, Y. L., Guo, T. Y. 2014; 4 (10): 803-813

    Abstract

    Guastello's polynomial regression method for solving cusp catastrophe model has been widely applied to analyze nonlinear behavior outcomes. However, no statistical power analysis for this modeling approach has been reported probably due to the complex nature of the cusp catastrophe model. Since statistical power analysis is essential for research design, we propose a novel method in this paper to fill in the gap. The method is simulation-based and can be used to calculate statistical power and sample size when Guastello's polynomial regression method is used to cusp catastrophe modeling analysis. With this novel approach, a power curve is produced first to depict the relationship between statistical power and samples size under different model specifications. This power curve is then used to determine sample size required for specified statistical power. We verify the method first through four scenarios generated through Monte Carlo simulations, and followed by an application of the method with real published data in modeling early sexual initiation among young adolescents. Findings of our study suggest that this simulation-based power analysis method can be used to estimate sample size and statistical power for Guastello's polynomial regression method in cusp catastrophe modeling.

    View details for PubMedID 27158562

  • Fatigability Disrupts Cognitive Processes' Regulation of Inflammatory Reactivity in Old Age AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Lin, F., Roiland, R., Polesskaya, O., Chapman, B., Johnson, M., Brasch, J., Chen, D., Mapstone, M. 2014; 22 (12): 1544-1554

    Abstract

    High fatigability, a dysfunctional adaption to fatigue, may lead to difficulties performing otherwise regularly encountered cognitive activities and may be related to pro-inflammatory reactivity. The purpose of the study was to investigate the effect of fatigability on cognitive processes and inflammatory response after an acute cognitive stress task in older adults.In an observational stress reactivity study conducted in a light- and temperature-controlled laboratory, we measured IL-6, self-reported acute fatigue, and frontally oriented cognitive processes in 55 community-dwelling individuals aged 75 years or older as part of a demanding set of cognitive tasks intended to induce stress.Subjects were classified into groups of low and high fatigability based on cluster analysis of their self-report acute fatigue before and after the cognitive tasks. The two clusters were comparable on levels of baseline IL-6 and cognitive processes; however, the high fatigability cluster had significantly higher levels of IL-6 response than the low fatigability cluster. After controlling for multiple covariates, fatigability moderated the relationship between speed of processing and IL-6 reactivity. Further exploratory analyses indicated significant adverse associations between speed of processing and attention and IL-6 reactivity in the group with low but not high fatigability.Although observational, these data are consistent with the notion that pro-inflammatory states in older adults might be reduced by improvements in cognitive processes. Because fatigability was associated with increased acute inflammatory response and disrupted the normal stress regulation provided by the cognitive processes, future randomized studies might examine whether fatigability alleviation reduces IL-6.

    View details for DOI 10.1016/j.jagp.2013.12.003

    View details for Web of Science ID 000345118500020

    View details for PubMedID 24388221

    View details for PubMedCentralID PMC4048650

  • EXECUTIVE HOMEOSTATIC NETWORK IN MILD COGNITIVE IMPAIRMENT Lin, F., Cole, D., Cotton, K. OXFORD UNIV PRESS INC. 2014: 78
  • Frequency of Mentally Stimulating Activities Modifies the Relationship Between Cardiovascular Reactivity and Executive Function in Old Age AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Lin, F., Heffner, K., Mapstone, M., Chen, D., Porsteisson, A. 2014; 22 (11): 1210-1221

    Abstract

    Recent evidence suggests that younger and middle-age adults who show greater cardiovascular reactivity (CVR) to acute mental stress demonstrate better reasoning and memory skills. The purpose of this study was to examine whether older adults would exhibit a similar positive association between CVR and executive function and whether regular engagement in mentally stimulating activities (MSA) would moderate this association.Secondary cross-sectional analysis.Three clinical research centers in the Midwest and on the West Coast and East Coast.A total of 487 older adults participating in an ongoing national survey.Heart rate (HR) and low-frequency (LF) and high-frequency (HF) domains of heart rate variability (HRV) were measured at baseline and in response to standard mental stress tasks (Stroop color word task and mental arithmetic). Executive function was measured separately from the stress tasks by using five neuropsychological tests. MSA was measured by self-reported frequency of six common MSA.Higher HR reactivity was associated with better executive function after controlling for demographic and health characteristics and baseline HR, and the interaction between HR reactivity and MSA was significant for executive function. Higher LF-HRV reactivity was also associated with executive function, but subsequent analyses indicated that frequency of MSA was the strongest predictor of executive function in models that included LF-HRV or HF-HRV.Higher HR reactivity to acute psychological stress is related to better executive function in older adults. For those with lower HR reactivity, engaging frequently in MSA produced compensatory benefits for executive function.

    View details for DOI 10.1016/j.jagp.2013.04.002

    View details for Web of Science ID 000343856600017

    View details for PubMedID 23891367

    View details for PubMedCentralID PMC3900591

  • Evaluation of objective and perceived mental fatigability in older adults with vascular risk JOURNAL OF PSYCHOSOMATIC RESEARCH Lin, F., Roiland, R., Heffner, K., Johnson, M., Chen, D., Mapstone, M. 2014; 76 (6): 458-464

    Abstract

    Mental fatigability refers to the failure to sustain participation in tasks requiring mental effort. Older adults with vascular risk are at particular risk for experiencing mental fatigability. The present study (1) tested a new way of measuring objective mental fatigability by examining its association with perceived mental fatigability; and (2) identified associated psychological, physiological, and situational predictors.A cross-sectional study was conducted with 49 community-dwelling participants aged 75+ years with vascular risk. A 20-minute fatigability-manipulation task was used to induce mental fatigability and develop objective and perceived mental fatigability measures. Objective fatigability was calculated by the change of reaction time over the course of the task. Perceived fatigability was calculated by the change of fatigue self-reported before and after the task. A set of potential psychological, physiological, and situational predictors were measured.There was a significant increase in reaction time and self-reported fatigue to the fatigability manipulation task, indicating occurrence of objective and perceived mental fatigability. Reaction time and self-reported fatigue were moderately, but significantly correlated. Higher levels of executive control and having a history of more frequently engaging in mental activities were associated with lower objective mental fatigability. None of the examined factors were associated with perceived mental fatigability.Objective and perceived mental fatigability were sensitive to our fatigability-manipulation task. While these two measures were correlated, they were not associated with the same factors. These findings need to be validated in studies with a more heterogeneous sample and a greater variety of fatigability-manipulation tasks.

    View details for DOI 10.1016/j.jpsychores.2014.04.001

    View details for Web of Science ID 000336639300004

    View details for PubMedID 24840140

    View details for PubMedCentralID PMC4033905

  • Cusp Catastrophe Model A Nonlinear Model for Health Outcomes in Nursing Research NURSING RESEARCH Chen, D., Lin, F., Chen, X., Tang, W., Kitzman, H. 2014; 63 (3): 211-220

    Abstract

    Although health outcomes may have fundamentally nonlinear relationships with relevant behavioral, psychological, cognitively, or biological predictors, most analytical models assume a linear relationship. Furthermore, some health outcomes may have multimodal distributions, but most statistical models in common use assume a unimodal, normal distribution. Suitable nonlinear models should be developed to explain health outcomes.The aim of this study is to provide an overview of a cusp catastrophe model for examining health outcomes and to present an example using grip strength as an indicator of a physical functioning outcome to illustrate how the technique may be used. Results using linear regression, nonlinear logistic model, and the cusp catastrophe model were compared.Data from 935 participants from the Survey of Midlife Development in the United States (MIDUS) were analyzed. The outcome was grip strength; executive function and the inflammatory cytokine interleukin-6 were predictor variables.Grip strength was bimodally distributed. On the basis of fit and model selection criteria, the cusp model was superior to the linear model and the nonlinear logistic regression model. The cusp catastrophe model identified interleukin-6 as a significant asymmetry factor and executive function as a significant bifurcation factor.The cusp catastrophe model is a useful alternative for explaining the nonlinear relationships commonly seen between health outcome and its predictors. Considerations for the use of cusp catastrophe model in nursing research are discussed and recommended.

    View details for DOI 10.1097/NNR.0000000000000034

    View details for Web of Science ID 000336252000009

    View details for PubMedID 24785249

    View details for PubMedCentralID PMC4066972

  • Associations between depressive symptoms and memory deficits vary as a function of insulin-like growth factor (IGF-1) levels in healthy older adults PSYCHONEUROENDOCRINOLOGY Lin, F., Suhr, J., Diebold, S., Heffner, K. L. 2014; 42: 118-123

    Abstract

    Accumulating evidence suggests an adverse association between depressive symptoms and cognition, but a positive association between insulin-like growth factor (IGF)-1 and cognition. The present study examined the influence of IGF-1 in the relationship between depressive symptoms and learning and memory.A cross-sectional study of 94 healthy fit older adults. Blood was collected and plasma IGF-1 was measured. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS), and learning and memory were assessed using the Rey Auditory Verbal Learning Test (AVLT).Among older adults with lower IGF-1 levels, higher depressive symptoms scores were associated with lower AVLT delayed recall and recognition. Older adults with higher IF-1 levels showed no associations between depressive symptoms and memory.The association between depressive symptoms and cognition is stronger among older adults with lower levels of circulating IGF-1. Further validation studies on groups with depression or different stages of cognitive impairment are needed. IGF-1 may be a novel intervention target for slowing cognitive decline in older adults with depressive symptoms.

    View details for DOI 10.1016/j.psyneuen.2014.01.006

    View details for Web of Science ID 000334000200013

    View details for PubMedID 24636508

    View details for PubMedCentralID PMC3996826

  • Profiles of Objective and Self- and Informant-Reported Language Abilities in Older Adults with Mild Cognitive Impairment Johnson, M., Lin, F., Hauenstein, E., Porsteinnson, A. LIPPINCOTT WILLIAMS & WILKINS. 2014: E63-E64
  • Longitudinal Effects of Metabolic Syndrome on Alzheimer and Vascular Related Brain Pathology DEMENTIA AND GERIATRIC COGNITIVE DISORDERS EXTRA Lin, F., Lo, R. Y., Cole, D., Ducharme, S., Chen, D., Mapstone, M., Porsteinsson, A., Alzheimers Dis Neuroimaging Initi 2014; 4 (2): 184-194

    Abstract

    This study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)].The study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238) from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multi-center prospective cohort. Confirmatory factor analysis was employed to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD) biomarkers, namely [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) regions of interest and medial temporal lobe volume over 5 years. A cerebrovascular aging index, cerebral white matter (cWM) volume, was examined as a comparison.The vascular risk was similar in all groups. Applying generalized estimating equation modeling, all brain-aging indices declined significantly over time. Higher MetS scores were associated with a faster decline of cWM in the CN and maMCI groups but with a slower decrement of regional glucose metabolism in FDG-PET in the saMCI and maMCI groups.At the very early stage of cognitive decline, the vascular burden such as MetS may be in parallel with or independent of AD pathology in contributing to cognitive impairment in terms of accelerating the disclosure of AD pathology.

    View details for DOI 10.1159/000363285

    View details for Web of Science ID 000218962000009

    View details for PubMedID 25337075

    View details for PubMedCentralID PMC4187257

  • Communication Difficulty and Relevant Interventions in Mild Cognitive Impairment Implications for Neuroplasticity TOPICS IN GERIATRIC REHABILITATION Johnson, M., Lin, F. 2014; 30 (1): 18-34

    Abstract

    Mild Cognitive Impairment (MCI) represents a critical point for controlling cognitive decline. Patterns of communication difficulty have been observed in patients with MCI and warrant examination and management. The present systematic review examined (1) characteristics of communication difficulty in MCI by focusing on two domains: expressive and receptive communication, and (2) cognitive interventions that addressed communication difficulties in individuals with MCI. Of the 28 observational studies we reviewed, expressive and receptive communications were generally impaired in individuals with MCI, compared to their healthy counterparts. However, only one of seven interventions effectively improved communication related outcomes. We finished the paper with a discussion about how neuroplasticity influences communication abilities in individuals with MCI to inform the future development of interventions for communication difficulty.

    View details for DOI 10.1097/TGR.0000000000000001

    View details for Web of Science ID 000335564300005

    View details for PubMedID 25356002

    View details for PubMedCentralID PMC4209953

  • EXECUTIVE FUNCTION, STRESS REGULATION, AND FRAILTY IN OLDER ADULTS WITH METABOLIC SYNDROME Lin, F., Roiland, R., Chen, D. OXFORD UNIV PRESS INC. 2013: 316-317
  • Trajectories of Combined Laboratory- and Real World-Based Speed of Processing in Community-Dwelling Older Adults JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Lin, F., Chen, D., Vance, D., Mapstone, M. 2013; 68 (3): 364-373

    Abstract

    To characterize the trajectories of laboratory- and real world-based speed of processing (SOP) over 5 years using finite latent growth mixture modeling, and to explore associated baseline individual-level predictors and functional outcomes in 2,802 community-dwelling older adults from the Advanced Cognitive Training for Independent and Vital Elderly cohort.Laboratory- and real world-based SOP and functional outcomes were assessed over 5 years, and candidate individual-level predictors were collected at baseline.After controlling for intervention assignment and demographic information, 4 distinct trajectories were identified: 4.6% of older adults had poor laboratory-based SOP and very poor real world-based SOP that both declined substantially over time; 17.9% had poor laboratory- and real world-based SOP that declined moderately; 38.7% had neutral laboratory- and real world-based SOP that maintained stable; and 37.9% had good laboratory- and real world-based SOP that declined slightly. Non-White, depression, subjective memory complaints, and vascular factors predicted the trajectories. The trajectories significantly differed in the rate of decline in basic activities of daily living, instrumental activities of daily living, and grip strength over time.Heterogeneous trajectories of SOP exist in old age. Future interventions addressing SOP should target the vulnerable group with poor SOP over time.

    View details for DOI 10.1093/geronb/gbs075

    View details for Web of Science ID 000318081800006

    View details for PubMedID 22967505

    View details for PubMedCentralID PMC3627655

  • Trajectories of Combined Laboratory- and Real World-Based Speed of Processing in Community-Dwelling Older adults; Predictors and Functional Outcomes Lin, F., Chen, D., Mapstone, M., Vance, D. LIPPINCOTT WILLIAMS & WILKINS. 2013: E110
  • Longitudinal relationships between subjective fatigue, cognitive function, and everyday functioning in old age INTERNATIONAL PSYCHOGERIATRICS Lin, F., Chen, D., Vance, D. E., Ball, K. K., Mapstone, M. 2013; 25 (2): 275-285

    Abstract

    The present study examined the prospective relationships between subjective fatigue, cognitive function, and everyday functioning.A cohort study with secondary data analysis was conducted using data from 2,781 community-dwelling older adults without dementia who were enrolled to participate in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized intervention trial. Measures included demographic and health information at baseline, and annual assessments of subjective fatigue, cognitive function (i.e. speed of processing, memory, and reasoning), and everyday functioning (i.e. everyday speed and everyday problem-solving) over five years.Four distinct classes of subjective fatigue were identified using growth mixture modeling: one group complaining fatigue "some of the time" at baseline but "most of the time" at five-year follow-up (increased fatigue), one complaining fatigue "a good bit of the time" constantly over time (persistent fatigue), one complaining fatigue "most of the time" at baseline but "some of the time" at five-year follow-up (decreased fatigue), and the fourth complaining fatigue "some of the time" constantly over time (persistent energy). All domains of cognitive function and everyday functioning declined significantly over five years; and the decline rates, but not the baseline levels, differed by the latent class of subjective fatigue. Except for the decreased fatigue class, there were different degrees of significant associations between the decline rates of subjective fatigue and all domains of cognitive function and everyday functioning in other classes of subjective fatigue.Future interventions should address subjective fatigue when managing cognitive and functional abilities in community-dwelling older adults.

    View details for DOI 10.1017/S1041610212001718

    View details for Web of Science ID 000312529100014

    View details for PubMedID 23083533

    View details for PubMedCentralID PMC3552486

  • Caring for Older Adults with Mild Cognitive Impairment An Update for Nurses JOURNAL OF GERONTOLOGICAL NURSING Lin, F., Vance, D. E., Gleason, C. E., Heidrich, S. M. 2012; 38 (12): 22-37

    Abstract

    Mild cognitive impairment (MCI) is a mild decline in single or multiple cognitive domains, while global cognition and basic activities of daily living remain intact. Nurses play an important role in early detection of MCI and providing care to maintain maximum independence for individuals with MCI. This article seeks to provide nurses with a review of the most recent research regarding the etiology and diagnosis of MCI, related risk and protective factors, patient and family experiences, and current interventions. This update provides research evidence to inform nursing practice of MCI care.

    View details for DOI 10.3928/00989134-20121106-03

    View details for Web of Science ID 000313043700006

    View details for PubMedID 23189995

    View details for PubMedCentralID PMC3587112

  • TRAJECTORIES OF COMBINED LABORATORY- AND EVERYDAY-BASED SPEED OF PROCESSING IN COMMUNITY-DWELLING OLDER ADULTS Lin, F., Chen, D., Vance, D., Mapstone, M. OXFORD UNIV PRESS INC. 2012: 92
  • Neuroplasticity and Successful Cognitive Aging: A Brief Overview for Nursing JOURNAL OF NEUROSCIENCE NURSING Vance, D. E., Kaur, J., Fazeli, P. L., Talley, M. H., Yuen, H. K., Kitchin, B., Lin, F. 2012; 44 (4): 218-227

    Abstract

    The brain remains dynamic even in older age and can benefit from mental exercises. Thus, it is important to understand the concepts of positive and negative neuroplasticity and how these mechanisms either support or detract from cognitive reserve. This article provides a brief review of these key concepts using four exemplary studies that clearly show the effects that these neurological mechanisms exert on cognitive reserve and cognitive functioning. From this review, a working knowledge of how neuroplasticity and cognitive reserve are expressed in patients will be provided along with how this information can be incorporated into nursing practice and research.

    View details for DOI 10.1097/JNN.0b013e3182527571

    View details for Web of Science ID 000306112400007

    View details for PubMedID 22743813

    View details for PubMedCentralID PMC3828033

  • Illness Representations in Older Adults with Mild Cognitive Impairment RESEARCH IN GERONTOLOGICAL NURSING Lin, F., Gleason, C. E., Heidrich, S. M. 2012; 5 (3): 195-206

    Abstract

    Little is known about patients' understanding of a diagnosis of mild cognitive impairment (MCI). The purpose of this cross-sectional descriptive study was to describe beliefs about MCI in people diagnosed with the condition and examine correlates (demographic and health) of those beliefs. Thirty individuals diagnosed with MCI completed the Illness Perception Questionnaire-MCI (IPQ-MCI), measuring eight domains of beliefs about MCI, and one scale of emotional distress. Five of them also participated in a 15-minute cognitive interview to explore responses to the IPQ-MCI. Participants correctly identified symptoms related to MCI; generally attributed MCI to aging, heredity, and abnormal brain changes; and believed MCI to be chronic, predictable, and controllable, causing little emotional distress. However, there were no consistent beliefs regarding the negative consequences of MCI or whether MCI was understandable. There were few significant correlates of beliefs. People with MCI are able to report their beliefs about their illness, suggesting that misconceptions and gaps in knowledge can be identified and addressed with nursing interventions.

    View details for DOI 10.3928/19404921-20120605-04

    View details for Web of Science ID 000306870500006

    View details for PubMedID 22716654

    View details for PubMedCentralID PMC3725767

  • Effect of leisure activities on inflammation and cognitive function in an aging sample ARCHIVES OF GERONTOLOGY AND GERIATRICS Lin, F., Friedman, E., Quinn, J., Chen, D., Mapstone, M. 2012; 54 (3): E398-E404

    Abstract

    Cardiovascular disease risk factors (CVDRFs) increase the risk of dementia. The purpose of this study was to examine whether leisure activities (mental, physical, and social activities) modified the effect of CVDRFs on inflammatory markers and cognitive function in middle and old age. A secondary-data analysis study was conducted using data from 405 middle-age participants (40-59 years) and 342 old-age participants (60-84 years) who participated in the Survey of Midlife Development in the United States (MIDUS). CVDRFs were obtained from a combination of self-report medical history and blood-based biomarkers. Three CVDRF groups (≤1, 2, and ≥3 CVDRFs) were identified. More CVDRFs were significantly associated with higher levels of inflammatory markers in both age groups, and associated with lower levels of executive function (EF) in the old age group. CVDRFs were not related to the frequency of leisure activities in either age group. After controlling for covariates, higher levels of physical activities were significantly associated with lower levels of inflammatory markers, and higher levels of mental activities were associated with higher levels of cognitive function. In the old age group, physical activities also moderated the effect of CVDRFs on episodic memory (EM), and mental activities moderated the effect of CVDRFs on interleukin-6 (IL-6). Multiple CVDRFs may be associated with poorer cognitive function and higher inflammatory markers, but middle-age and older adults with CVDRFs may not engage in frequent physical and cognitive activities that may be protective. It is important to develop strategies to facilitate engagement in these activities from midlife.

    View details for DOI 10.1016/j.archger.2012.02.002

    View details for Web of Science ID 000302959400023

    View details for PubMedID 22377120

    View details for PubMedCentralID PMC3331938

  • Role of older adult's illness schemata in coping with Mild Cognitive Impairment JOURNAL OF PSYCHOSOMATIC RESEARCH Lin, F., Heidrich, S. M. 2012; 72 (5): 357-363

    Abstract

    1) To describe the illness representations of older persons with Mild Cognitive Impairment (MCI); 2) to describe how older adults cope with MCI; 3) to examine the relationships between illness representations and coping.Sixty-three older adults with MCI completed questionnaires on demographic and health information, beliefs about MCI (Illness Perception Questionnaire-MCI), and coping with MCI (brief COPE and Self-care Behaviors Checklist).Participants endorsed an average of 7 symptoms that they experienced and believed were related to MCI and an average of 7 potential causes of MCI. Participants tended to believe MCI was chronic, not cyclic, and controllable, but they differed in their beliefs about the consequences, understandability and emotional impact of MCI. Participants used many dementia prevention behaviors and memory aids, some problem-focused and emotion-focused coping strategies, and few dysfunctional coping strategies. Cluster analysis identified three clusters of beliefs about MCI: "few symptoms and positive beliefs," "moderate symptoms and positive beliefs," and "many symptoms and negative beliefs." Those in the "many symptoms and negative beliefs" cluster had significantly more negative beliefs about the consequences, unpredictability (cyclic timeline), and emotional impact of MCI than those in the other clusters. Participants in the "few symptoms and positive beliefs" cluster used significantly fewer memory aids, problem-focused coping strategies, emotion-focused coping strategies, and dysfunctional coping than those in the other two clusters.As suggested by the Common Sense Model, older adults with MCI have beliefs about their MCI and these beliefs are associated with how older adults cope with MCI.

    View details for DOI 10.1016/j.jpsychores.2012.01.008

    View details for Web of Science ID 000302761200004

    View details for PubMedID 22469277

  • Baseline Purpose Oriented Life and Cognitive Outcomes Lin, F., Topazian, H., Geda, Y. LIPPINCOTT WILLIAMS & WILKINS. 2012
  • COPING IN OLDER INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT Lin, F., Hanna, L., Heidrich, S. M. OXFORD UNIV PRESS INC. 2011: 164
  • ILLNESS REPRESENTATIONS, COPING, AND HEALTH OUTCOMES IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT Lin, F., Heidrich, S. M. OXFORD UNIV PRESS INC. 2011: 163-164
  • Pain Management and Patient Outcomes among Hospitalized Geriatric Patients Lin, F., Kim, B., Pellino, T., Brenny-Fitzpatrick, M., Siebers, M., Gordon, D. WILEY-BLACKWELL. 2011: S184
  • Developing Quality Indicators (QIs) for Delirium, Depression and Dementia (3Ds) Recommendations of the Acute Care for Elders (ACE) Interdisciplinary Consult Team: Modification of the Assessing Care of Vulnerable Elders (ACOVE-3) Measures. Lin, F., Brenny-Fitzpatrick, M., Siebers, M. WILEY-BLACKWELL PUBLISHING, INC. 2010: 172
  • University of Wisconsin Geriatrics Transitional Care Program: Minimizing Health Resources, Maximizing Care Continuity. Grau, B., Siebers, M., Kind, A., Hansen, K., Addington-White, J., Lin, F., Asthana, S. WILEY-BLACKWELL PUBLISHING, INC. 2010: 116
  • Awareness of Memory Abilities in Community-Dwelling Older Adults with Suspected Dementia and Mild Cognitive Impairment DEMENTIA AND GERIATRIC COGNITIVE DISORDERS Lin, F., Wharton, W., Dowling, N., Ries, M. L., Johnson, S. C., Carlsson, C. M., Asthana, S., Gleason, C. E. 2010; 30 (1): 83-92

    Abstract

    To examine awareness of memory abilities by groups (healthy control, suspected dementia/mild cognitive impairment, MCI, and diagnosed dementia/MCI), and to describe group differences in the relationship between awareness and cognitive performance in a community sample.In a cross-sectional design, 183 subjects were evaluated in a community setting and categorized into 3 groups based on their cognitive performance and reported medical history. Awareness of memory abilities was quantified using a published anosognosia ratio (AR) comparing the estimated to the objective memory performance by subjects. Each group was further categorized into 'overestimators', 'accurate estimators', and 'underestimators' based on their AR scores.The suspected and diagnosed dementia/MCI groups had significantly higher AR scores than the controls. The suspected group also had a significantly larger proportion (96.2%) of overestimators than the diagnosed (73.3%) and control groups (26.1%). Impaired awareness in overestimators of the suspected and diagnosed groups was correlated with deficits in executive function, language or global cognition.Impaired awareness of memory abilities was prevalent in community-dwelling older adults with suspected and diagnosed dementia or MCI. Those with suspected dementia or MCI were more likely to overestimate their memory abilities than their diagnosed counterparts, suggesting that limited awareness of deficits may hinder utilization of dementia diagnostic services.

    View details for DOI 10.1159/000318752

    View details for Web of Science ID 000280936900014

    View details for PubMedID 20714155

    View details for PubMedCentralID PMC3214821

  • ILLNESS PERCEPTIONS IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT: A FEASIBILITY STUDY Lin, F., Gleason, C., Heidrich, S. M. GERONTOLOGICAL SOC AMER. 2009: 91
  • Does psychological well-being mediate the effects of symptoms on function in older breast cancer survivors? Lin, F., Heidrich, S. JOHN WILEY & SONS LTD. 2008: S38-S39