Joe Winer completed his PhD in Psychology at UC Berkeley working with Matthew Walker and William Jagust. During his PhD, Joe used overnight EEG and PET imaging to investigate connections between sleep disruption and Alzheimer's disease in the context of healthy aging. At Stanford, Joe's research combines wearable devices, neuroimaging, and other biomarkers to explore how tracking sleep and other factors in everyday life can provide information about brain health and cognitive trajectories in aging and neurodegenerative diseases.
Honors & Awards
NRSA F31 Fellowship, NIA (2019-2020)
NRSA F32 Fellowship, NIA (2021-2024)
REC Fellow, Stanford Alzheimer's Disease Research Center (ADRC) (2021-2023)
Doctor of Philosophy, University of California Berkeley (2020)
Master of Arts, University of Chicago (2013)
Bachelor of Arts and Science, McGill University (2011)
Elizabeth Mormino, Postdoctoral Faculty Sponsor
Association of Short and Long Sleep Duration With Amyloid-beta Burden and Cognition in Aging.
Importance: Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid beta [Abeta]), depression, and cardiovascular disease.Objective: To investigate the associations between self-reported sleep duration and brain Abeta burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition.Design, Setting, and Participants: This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Abeta positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021.Main Outcomes and Measures: The outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Abeta burden (as measured with a fluorine 18-labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables.Results: The 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Abeta burden (beta [SE]=-0.01 [0.00]; P=.005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Abeta was found between long and normal sleep duration groups (beta [SE]=0.00[0.01]; P=.99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: beta [SE]=0.48 [0.17], P=.01; long vs normal sleep duration: beta [SE]=0.97 [0.31], P=.002), depressive symptoms (short vs normal sleep duration: beta [SE]=0.31 [0.05], P<.001; long vs normal sleep duration: beta [SE]=0.39 [0.09], P<.001), and daytime napping (short vs normal sleep duration: beta [SE]=2.66 [0.77], P=.001; long vs normal sleep duration: beta [SE]=3.62 [1.38], P=.01). Long sleep duration was associated with worse performance across multiple cognitive domains.Conclusions and Relevance: In this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Abeta burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.
View details for DOI 10.1001/jamaneurol.2021.2876
View details for PubMedID 34459862
Tau and beta-amyloid burden predict actigraphy-measured and self-reported impairment and misperception of human sleep.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Alzheimer's disease (AD) is associated with poor sleep, but the impact of tau and beta-amyloid (Abeta) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Abeta predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received 18F-FTP-tau and 11C-PIB-Abeta PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Abeta, was associated with markedly worse objective sleep. In contrast, Abeta and tau were associated with worse self-reported sleep quality. Of clinical relevance, Abeta burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals under-estimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Abeta deposition are linked with distinct phenotypes of real-world sleep impairment, one that includes a cognitive misperception of their own sleep health.Significance StatementAlzheimer's disease is associated with sleep disruption, often before significant memory decline. Thus real-life patterns of sleep behavior have the potential to serve as a window into early disease progression. In 89 cognitive healthy older adults, we found that tau burden was associated with worse wristwatch actigraphy-measured sleep quality, and that both tau and beta-amyloid were independently predictive of self-reported sleep quality. Furthermore, individuals with greater beta-amyloid deposition were more likely to underestimate their sleep quality, and sleep quality underestimation was associated with worse executive function. These data support the role of sleep impairment as a key marker of early Alzheimer's disease, and offer the possibility that actigraphy may be an affordable and scalable tool in quantifying Alzheimer's-related behavioral changes.
View details for DOI 10.1523/JNEUROSCI.0353-21.2021
View details for PubMedID 34290080
Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years.
Current biology : CB
2020; 30 (21): 4291-4298.e3
Experimental sleep-wake disruption in rodents and humans causally modulates β-amyloid (Aβ) dynamics (e.g., [1-3]). This leads to the hypothesis that, beyond cross-sectional associations, impaired sleep structure and physiology could represent prospective biomarkers of the speed with which Aβ accumulates over time. Here, we test the hypothesis that initial baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency) provide future forecasting sensitivity to the rate of Aβ accumulation over subsequent years. A cohort of clinically normal older adults was assessed using objective sleep polysomnography in combination with longitudinal tracking of Aβ accumulation with [11C]PiB positron emission tomography (PET) imaging. Both the proportion of NREM SWA below 1 Hz and the measure of sleep efficiency predicted the speed (slope) of subsequent Aβ deposition over time, and these associations remained robust when taking into account additional cofactors of interest (e.g., age, sex, sleep apnea). Moreover, these measures were specific, such that no other macro- and microphysiological architecture metrics of sleep demonstrated such sensitivity. Our data support the proposal that objective sleep markers could be part of a set of biomarkers that statistically forecast the longitudinal trajectory of cortical Aβ deposition in the human brain. Sleep may therefore represent a potentially affordable, scalable, repeatable, and non-invasive tool for quantifying of Aβ pathological progression, prior to cognitive symptoms of Alzheimer's disease (AD).
View details for DOI 10.1016/j.cub.2020.08.017
View details for PubMedID 32888482
View details for PubMedCentralID PMC7642104
Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience
2019; 39 (32): 6315-6324
Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and β-amyloid (Aβ). Here we combined PET measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. Aβ burden was not associated with coupling impairment but instead predicted the diminished amplitude of <1 Hz slow-wave-activity, results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life Aβ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential noninvasive, cost-effective, and scalable biomarkers (current and future forecasting) of AD pathology, and carry both therapeutic and public health implications.SIGNIFICANCE STATEMENT Several studies have linked sleep disruption to the progression of Alzheimer's disease (AD). Tau and β-amyloid (Aβ), the primary pathological features of AD, are associated with both objective and subjective changes in sleep. However, it remains unknown whether late life tau and Aβ burden are associated with distinct impairments in sleep physiology or changes in sleep across the lifespan. Using polysomnography, retrospective questionnaires, and tau- and Aβ-specific PET, the present study reveals human sleep signatures that dissociably predict levels of brain tau and Aβ in older adults. These results suggest that a night of polysomnography may aid in evaluating tau and Aβ burden, and that treating sleep deficiencies within decade-specific time windows may serve in delaying AD progression.
View details for DOI 10.1523/JNEUROSCI.0503-19.2019
View details for PubMedID 31209175
View details for PubMedCentralID PMC6687908
Waking Up to the Importance of Sleep in the Pathogenesis of Alzheimer Disease.
2018; 75 (6): 654-656
View details for DOI 10.1001/jamaneurol.2018.0005
View details for PubMedID 29532083
Associations Between Tau, β-Amyloid, and Cognition in Parkinson Disease.
2018; 75 (2): 227-235
Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia.To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia.This cross-sectional study recruited 30 patients with Parkinson disease (15 with PD-CN and 15 with PD-MCI) from a tertiary care medical center and research institutions from July 2015 through October 2016. One patient with PD-MCI did not receive a magnetic resonance imaging scan and thus was excluded from all analyses; 29 patients with PD were included in the present study. Participants underwent tau positron emission tomographic (PET) scanning with fluorine 18-labeled AV-1451, Aβ PET scanning with carbon 11-labeled Pittsburgh compound B, magnetic resonance imaging, cognitive testing, and neurologic evaluation. Imaging measures were compared with 49 healthy control participants.Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. We hypothesized that tau aggregation across groups would be related to age and Aβ status.Of the 78 participants, 47 (60%) were female, and the mean (SD) age was 71.1 (6.6) years. Six patients with PD (21%) were Aβ-positive, of whom 1 was mildly cognitively impaired; 23 were Aβ-negative (79%). (Of the 49 healthy controls, 25 were Aβ-negative and 24 Aβ-positive.) Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and additionally between all patients with PD and Aβ-negative controls, did not reveal significant differences. Tau PET binding did not differ between patients with PD-MCI and PD-CN in brain regions reflecting Alzheimer disease Braak stages 1/2, 3/4, or 5/6, and did not differ from Aβ-negative healthy older adults. Mean (SD) tau PET binding was significantly elevated in Aβ-positive patients with PD relative to Aβ-negative patients with PD within brain regions reflecting Alzheimer disease Braak stage 3/4 (1.22 [0.07] vs 1.14 [0.07]; P = .03) and Braak stage 5/6 (1.20 [0.07] vs 1.11 [0.08]; P = .02).These findings suggest that patterns of cortical Aβ and tau do not differ in people with PD-CN, people with PD-MCI, and healthy older adults. Age, Aβ, and tau do not differentiate patients with PD-CN and PD-MCI. Tau deposition is related to Aβ status and age in both people with PD and healthy older adults. Cognitive deficits in people with PD without dementia do not appear to reflect measureable Alzheimer disease.
View details for DOI 10.1001/jamaneurol.2017.3713
View details for PubMedID 29228071
View details for PubMedCentralID PMC5838622
Sleep and Human Aging.
2017; 94 (1): 19-36
Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need?
View details for DOI 10.1016/j.neuron.2017.02.004
View details for PubMedID 28384471
View details for PubMedCentralID PMC5810920
Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?
Trends in neurosciences
2016; 39 (8): 552-566
Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.
View details for DOI 10.1016/j.tins.2016.05.002
View details for PubMedID 27325209
View details for PubMedCentralID PMC4967375