Spira, Adam P.

Objective Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid β (Aβ) deposition and neurodegeneration. Whether vascular and Alzheimer disease‐associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. Methods Participants in the Atherosclerosis Risk in Communities–Positron Emission Tomography study were followed from 1987–1989 (45–64 years old) through 2016–2017 (74–94 years old), with repeat cognitive assessment and dementia adjudication. In 2011–2013, dementia‐free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aβ) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aβ standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. Results In 298 individuals, 36 developed dementia (median follow‐up = 4.9 years). Midlife hypertension and Aβ each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16–5.67; Aβ SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72–3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18–5.28) and Aβ independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03–2.20) and Aβ SUVR (HR = 2.52, 95% CI = 1.83–3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aβ and MVRFs (HR = 2.18, 95% CI = 1.18–4.01). Interpretation Midlife hypertension and late life Aβ are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607–619

Introduction The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, whether stressful life events are associated with subsequent cognitive decline has received scant research attention. Methods In Wave 3 (1993–1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004–2005), they completed the Mini Mental State Examination (MMSE) and a word‐list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4. Results A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex. Conclusions Unlike men, middle‐aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.

ObjectivesTo determine the association of napping intention, frequency, and duration with cognition in a nationally‐representative sample of US older adults.MethodsWe performed a cross‐sectional analysis of community‐dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013‐2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past‐month napping intention (intentional/unintentional), napping frequency (rarely/never [non‐nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31‐60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self‐rated memory (score: 1[excellent]‐5[very poor]).ResultsAfter adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non‐nappers (B = −0.23, P < 0.01) and intentional nappers (B = −0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self‐rated memory than non‐nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = −0.26, P < 0.05) and CDT scores (B = −0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate‐duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance.ConclusionsAmong older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

Abstract Approximately half of older people report sleep disturbances, which are associated with various health conditions, including neurodegenerative disease and dementia. Indeed, 60 to 70% of people with cognitive impairment or dementia have sleep disturbances, which are linked to poorer disease prognosis. Sleep disturbances in people with dementia have long been recognized and studied; however, in the past 10 years, researchers have begun to study disturbed sleep, including sleep fragmentation, abnormal sleep duration, and sleep disorders, as risk factors for dementia. In this review the authors summarize evidence linking sleep disturbance and dementia. They describe how specific aspects of sleep (e.g., quality, duration) and the prevalence of clinical sleep disorders (e.g., sleep-disordered breathing, rapid eye movement sleep behavior disorder) change with age; how sleep parameters and sleep disorders are associated with the risk of dementia; how sleep can be disturbed in dementia; and how disturbed sleep affects dementia prognosis. These findings highlight the potential importance of identifying and treating sleep problems and disorders in middle-aged and older adults as a strategy to prevent cognitive decline and dementia. The authors also review recent evidence linking sleep disturbances to the pathophysiology underlying dementing conditions, and briefly summarize available treatments for sleep disorders in people with dementia.