Rachel completed her BSc in Psychology and MSc in Brain Imaging and Cognitive Neuroscience at the University of Birmingham, UK. She then completed her PhD in Rehabilitation Sciences at the University of British Columbia, Canada under the supervision of Dr. Teresa Liu-Ambrose. Her PhD work utilised lesion network mapping to investigate the functional networks disrupted by cerebral small vessel disease, its relationships with cognitive and mobility impairment, and the use of resistance training to target disease progression. She is now a Postdoctoral Scholar in the Human Motor Control and Neuromodulation Lab under the supervision of Dr. Helen Bronte-Stewart. In this role, Rachel will use diverse neuroimaging methodologies to evaluate neural targets for deep brain stimulation to treat cognitive impairment in people with Parkinson’s Disease.
Doctor of Philosophy, University of British Columbia (2022)
Master of Science, University Of Birmingham (2016)
Bachelor of Science, University Of Birmingham (2015)
Helen Bronte-Stewart, Postdoctoral Faculty Sponsor
Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the"what," "for whom," and "how" of exercise to promote cognitive function
2022; 23 (1): 766
Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms.Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up).Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health.ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.
View details for DOI 10.1186/s13063-022-06699-7
View details for Web of Science ID 000852413200002
View details for PubMedID 36085237
View details for PubMedCentralID PMC9462619
Mind the gaps: functional networks disrupted by white matter hyperintensities are associated with greater falls risk
NEUROBIOLOGY OF AGING
2022; 109: 166-175
White matter hyperintensities (WMH) are associated with greater falls risk and slow gait speed. Whether these deficits are caused by the disruption of large-scale functional networks remains inconclusive. Further, physical activity moderates the association between WMHs and falls, but whether this extends to the disruption of functional networks remains unknown. One hundred and sixty-four adults (>55 years old) were included in this study. Using lesion network mapping, we identified significant correlations between the percentage of WMH-related disruption of the dorsal attention network and Physiological Profile Assessment (PPA) score (r = 0.24, p < 0.01); and between disruption of both the sensorimotor (r = 0.23, p < 0.01) and ventral attention networks (r = 0.21, p = 0.01) with foam sway. There were no significant associations with floor sway or gait speed. Physical activity moderated the association between the dorsal attention network and PPA score (p = 0.045). Thus, future research should investigate whether physical activity should be recommended in the clinical management of older adults with cerebral small vessel disease.
View details for DOI 10.1016/j.neurobiolaging.2021.09.023
View details for Web of Science ID 000717640300004
View details for PubMedID 34740078
Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults
FRONTIERS IN HUMAN NEUROSCIENCE
2021; 15: 671464
Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk. Methods: Seventy-six community-dwelling older adults aged 70-80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models. Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (β = -0.26 ± 0.11; p = 0.022) and WMH volume (β = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (β = -0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk. Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA.
View details for DOI 10.3389/fnhum.2021.671464
View details for Web of Science ID 000657498800001
View details for PubMedID 34093153
View details for PubMedCentralID PMC8175638
Painting by lesions: White matter hyperintensities disrupt functional networks and global cognition
2021; 236: 118089
White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p<.001) and ventral attention network (p <. 001) was significantly correlated with MoCA score. Thus, the greater the disruption to the sensorimotor and ventral attention networks, the poorer the global cognition. Our results reveal that the visual, ventral attention, and frontoparietal networks are most vulnerable to disruptions stemming from WMHs. Additionally, we identified that disruption to the sensorimotor and ventral attention networks, as a result of WMHs, may underlie deficits in global cognition in older adults with cerebral small vessel disease.
View details for DOI 10.1016/j.neuroimage.2021.118089
View details for Web of Science ID 000668960100014
View details for PubMedID 33882347
Reshaping the path of vascular cognitive impairment with resistance training: a study protocol for a randomized controlled trial
2021; 22 (1): 217
Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its modifiable risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities (WMHs), research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, the primary aim of this proof-of-concept randomized controlled trial is to investigate the efficacy of a 12-month, twice-weekly progressive resistance training program on cognitive function and WMH progression in adults with SIVCI. We will also assess the efficiency of the intervention.Eighty-eight community-dwelling adults, aged > 55 years, with SIVCI from metropolitan Vancouver will be recruited to participate in this study. SIVCI will be determined by the presence of cognitive impairment (Montreal Cognitive Assessment < 26) and cerebral small vessel disease using computed tomography or magnetic resonance imaging. Participants will be randomly allocated to a twice-weekly exercise program of (1) progressive resistance training or (2) balance and tone training (i.e., active control). The primary outcomes are cognitive function measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-13 with additional cognitive tests) and WMH progression.The burden of SIVCI is immense, and to our knowledge, this will be the first study to quantify the effect of progressive resistance training on cognitive function and WMH progression among adults with SIVCI. Slowing the rate of cognitive decline and WMH progression could preserve functional independence and quality of life. This could lead to reduced health care costs and avoidance of early institutional care.ClinicalTrials.gov NCT02669394 . Registered on February 1, 2016.
View details for DOI 10.1186/s13063-021-05156-1
View details for Web of Science ID 000631515700003
View details for PubMedID 33736706
View details for PubMedCentralID PMC7971404
Shining the Light on the MotionWatch8 Light Sensor for Sleep and Aging Research: What Can We Measure and What Are We Missing?
JOURNAL OF ALZHEIMERS DISEASE REPORTS
2021; 5 (1): 55-63
Poor sleep is common among older adults at risk for dementia and may be due to circadian dysregulation. Light is the most important external stimulus to the circadian clock and bright light therapy (BLT) has been used for >20 years to help realign circadian rhythms. However, the ability of field methods (e.g., actigraphy) to accurately determine the type and intensity of light is unknown.We examined the ability of the MotionWatch8 (MW8) light sensor to determine: 1) light versus dark, 2) electrical light versus daylight, and 3) device-based BLT versus light which was not BLT.We tested the MW8 under 17 daily light scenarios. Light exposure data was collected for 5 minutes during each scenario. Concurrently, we measured light exposure using the LT40 Light Meter, a sensitive measure of light intensity. We then developed individual cut-points using receiver operator characteristics analyses to determine optimal MW8 cut-points for 1) light versus dark; 2) electrical light versus daylight; and 3) light from a BLT box versus light which was not BLT. Bland-Altman plots tested the precision of the MW8 compared to the LT40.The MW8 accurately discriminated light versus dark (>32 lux), and electrical light versus daylight (<323 lux). However, the MW8 had poor accuracy for 1) discriminating BLT from light which was not BLT; and 2) low precision compared to the LT40.The MW8 appears to be able to discern light versus dark and electrical light versus daylight; however, there remains a need for accurate field methods capable of measuring light exposure.
View details for DOI 10.3233/ADR-200242
View details for Web of Science ID 000651079100007
View details for PubMedID 33681717
View details for PubMedCentralID PMC7903008
Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease
JOURNAL OF ALZHEIMERS DISEASE
2021; 80 (1): 91-101
Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood.The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD.This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05.After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β = -0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132).Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.
View details for DOI 10.3233/JAD-201134
View details for Web of Science ID 000627617100007
View details for PubMedID 33523006
Functional connectivity underpinning changes in life-space mobility in older adults with mild cognitive impairment: A 12-month prospective study
BEHAVIOURAL BRAIN RESEARCH
2020; 378: 112216
Subtle changes in mobility exist among older adults with mild cognitive impairment (MCI). Life-space mobility defines the frequency and extent of movements in the environment, and lower life-space mobility is associated with adverse health outcomes and MCI. Currently, the underlying mechanism of this association is not well understood. This study examined the functional neural correlates of life-space mobility in community-dwelling older adults with MCI. We first conducted a cross-sectional investigation of the association between resting-state default mode network (DMN) and sensori-motor network (SMN) connectivity and life-space mobility (assessed by the Life-Space Assessment (LSA)) among 60 community-dwelling older adults with MCI using aggregated data from two studies - baseline data from a randomized controlled trial (n = 20) and baseline data from a 12-month prospective study (n = 40). Using data from the 12-month prospective study (n = 35), we then examined whether baseline internetwork connectivity predicts reduced life-space mobility over 12 months. The cross-sectional analysis showed higher DMN-SMN connectivity was associated with lower LSA scores after adjusting for baseline global cognitive function and baseline age (p < 0.01). A significant reduction in LSA scores was observed in the 35 participants of the 12-month prospective study (paired sample t-test mean change = -6.53, p = 0.01). Greater baseline DMN-SMN connectivity was associated with greater reduction in life-space mobility at 12 months (p = 0.04) after adjusting for baseline age, global cognitive function, and LSA score. Our findings suggest that lower and reduced life-space mobility in older adults with MCI may be due to altered functional architecture of the brain such that normal neuro-cognitive motor behaviours may be disrupted.
View details for DOI 10.1016/j.bbr.2019.112216
View details for Web of Science ID 000526059200012
View details for PubMedID 31597084
Head over heels but I forget why: Disruptive functional connectivity in older adult fallers with mild cognitive impairment
BEHAVIOURAL BRAIN RESEARCH
2019; 376: 112104
Disrupted functional connectivity has been highlighted as a neural mechanism by which impaired cognitive function and mobility co-exist in older adults with mild cognitive impairment (MCI). The objective of this study was to determine the independent and combined effects of MCI and faller status on functional connectivity of three functional networks: default mode network (DMN), fronto-parietal network (FPN) and sensorimotor network (SMN) between 4 groups of older adults: 1) Healthy; 2) MCI without Falls; 3) Fallers without MCI; and 4) Fallers with MCI.Sixty-six adults aged 70-80 years old were included. Cognition was assessed using: 1) cognitive dual task; 2) Stroop Colour-Word Test; 3) Trail Making Tests (TMT); and 4) Digit Symbol Substitution Test (DSST). Postural sway was assessed with eyes opened and standing on the floor. Functional connectivity was measured using fMRI while performing a finger-tapping task.Differences in DMN-SMN connectivity were found for Fallers with MCI vs Fallers without MCI (p = .001). Fallers with MCI had significantly greater postural sway than the other groups. Both DMN-SMN connectivity (p = .03) and postural sway (p = .001) increased in a significantly linear fashion from Fallers without MCI, to MCI without Falls, to Fallers with MCI. Participants with MCI performed significantly worse on the DSST (p = .003) and TMT (p = .007) than those without MCI.Aberrant DMN-SMN connectivity may underlie reduced postural stability. Having both impaired cognition and mobility is associated with a greater level of disruptive DMN-SMN connectivity and increased postural sway than singular impairment.
View details for DOI 10.1016/j.bbr.2019.112104
View details for Web of Science ID 000526056500021
View details for PubMedID 31325516
Muscle strength is associated with cognition in chronic stroke
SAGE PUBLICATIONS LTD. 2019: 29
View details for Web of Science ID 000488946600126
Myelin breakdown is associated with cognitive dysfunction in mild cognitive impairment
SAGE PUBLICATIONS LTD. 2019: 32
View details for Web of Science ID 000488946600140
Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis
NEUROBIOLOGY OF AGING
2019; 79: 119-130
Exercise plays a key role in healthy aging by promoting both physical and cognitive function. Physical function and cognitive function appear to be interrelated and may share common mechanisms. Thus, exercise-induced improvements in physical function and cognitive function may co-occur and be associated with each other. However, no systematic review has specifically assessed and compared the effects of exercise on both physical function and cognitive function in older adults, and the association between changes in both outcomes after exercise training. Thus, we conducted a systematic review and meta-analysis (N = 48 studies) among older adults (60+ years). These data suggest exercise training has a significant benefit for both physical function (g = 0.39; p < 0.001) and cognitive function (g = 0.24; p < 0.001). At the study level, there was a positive correlation between the size of the exercise-induced effect on physical function and on cognitive function (b = 0.41; p = 0.002). Our results indicate exercise improves both physical and cognitive function, reiterating the notion that exercise is a panacea for aging well.
View details for DOI 10.1016/j.neurobiolaging.2019.03.007
View details for Web of Science ID 000472489600014
View details for PubMedID 31051329
The effects of an 8-week computerized cognitive training program in older adults: a study protocol for a randomized controlled trial
2018; 18: 31
Given the world's aging population, it is important to identify strategies that promote healthy cognitive aging and minimize cognitive decline. Currently, no curative pharmaceutical therapy exists for cognitive impairment and dementia. As a result, there is much interest in lifestyle approaches. Specifically, complex mental activity, such as cognitive training, may be a promising method to combat cognitive decline in older adults. As such, the industry of commercial computerized cognitive training (CCT) applications has rapidly grown in the last decade. However, the efficacy of these commercial products is largely not established. Moreover, exercise is a recognized strategy for promoting cognitive outcomes in older adults and may augment the efficacy of computerized cognitive training applications. Therefore, we propose a proof-of-concept randomized controlled trial (RCT) to examine the effect of a commercial CCT program in community-dwelling older adults.An 8-week RCT to examine the effect of a commercial CCT program, alone and preceded by a 15-min brisk walk, on cognitive function and explore the underlying neural mechanisms in adults aged 65-85 years old. Participants will be randomized to one of three intervention groups: 1) Computerized cognitive training (FBT); 2) A 15-min brisk walk followed by computerized cognitive training (Ex-FBT); or 3) A combination of educational classes, sham cognitive training, and balanced and tone exercises (active control, BAT). Participants in all intervention groups will attend three one-hour classes per week over the course of the intervention. Participants will be assessed at baseline, trial completion, and 1-year post study completion (1-year follow-up).If results from this study show benefits for cognition at trial completion, CCT programs, alone or in combination with walking, might be a strategy to promote healthy cognitive aging in older adults. In addition, results from the 1-year follow-up measurement could provide important information regarding the long-term benefits of these CCT programs.ClinicalTrials.gov Protocol Registration System: NCT02564809; registered September 1, 2015.
View details for DOI 10.1186/s12877-018-0730-6
View details for Web of Science ID 000423871700002
View details for PubMedID 29378515
View details for PubMedCentralID PMC5789628
Resting State Default Mode Network Connectivity, Dual Task Performance, Gait Speed, and Postural Sway in Older Adults with Mild Cognitive Impairment
FRONTIERS IN AGING NEUROSCIENCE
2017; 9: 423
Aging is associated with an increased risk of falling. In particular, older adults with mild cognitive impairment (MCI) are more vulnerable to falling compared with their healthy counterparts. Major contributors to this increased falls risk include a decline in dual task performance, gait speed, and postural sway. Recent evidence highlights the potential influence of the default mode network (DMN), the frontoparietal network (FPN), and the supplementary motor area (SMA) on dual task performance, gait speed, and postural sway. The DMN is active during rest and deactivates during task-oriented processes, to maintain attention and stay on task. The FPN and SMA are involved in top-down attentional control, motor planning, and motor execution. The DMN shows less deactivation during task in older adults with MCI. This lack of deactivation is theorized to increase competition for resources between the DMN and task-related brain regions (e.g., the FPN and SMA), increasing distraction from the task and reducing task performance. However, no study has yet investigated the relationship between the between-network connectivity of the DMN with these regions and dual task walking, gait speed or postural sway. We hypothesized that greater functional connectivity both within the DMN and between DMN-FPN and DMN-SMA, will be associated with poorer performance during dual task walking, slower gait speed, and greater postural sway in older adults with MCI. Forty older adults with MCI were measured on a dual task-walking paradigm, gait speed over a 4-m walk, and postural sway using a sway-meter. Greater within-DMN connectivity was significantly correlated with poorer dual task performance. Furthermore, greater inter-network connectivity between the DMN and SMA was significantly correlated with slower gait speed and greater postural sway on the eyes open floor sway task. Thus, greater resting state DMN functional connectivity may be an underlying neural mechanism for reduced dual task ability, slower gait speed, and greater postural sway, resulting in the increased risk of mobility disability and falling in older adults with MCI.
View details for DOI 10.3389/fnagi.2017.00423
View details for Web of Science ID 000418449500001
View details for PubMedID 29311906
View details for PubMedCentralID PMC5742581