Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia.
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ABSTRACT: Objective
To evaluate the association between sleep duration and the risk of incident dementia and brain aging.Methods
Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 ± 6 years, 57% women) as a 3-level variable: <6 hours (short), 6-9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance.Results
We observed 234 cases of all-cause dementia over 10 years of follow-up. In multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.24-3.26). These findings were driven by persons with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06-7.55) and persons without a high school degree (HR 6.05; 95% CI 3.00-12.18). Transitioning to sleeping >9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44-4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.17-4.13). Relative to sleeping 6-9 hours, long sleep duration was also associated cross-sectionally with smaller TCBV (β ± SE, -1.08 ± 0.41 mean units of TCBV difference) and poorer executive function (β ± SE, -0.41 ± 0.13 SD units of Trail Making Test B minus A score difference).Conclusions
Prolonged sleep duration may be a marker of early neurodegeneration and hence a useful clinical tool to identify those at a higher risk of progressing to clinical dementia within 10 years.
SUBMITTER: Westwood AJ
PROVIDER: S-EPMC5373785 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo analyze potential markers in sleep for early recognition of neurodegenerative disease in newly diagnosed, unmedicated patients with Parkinson disease (PD) compared to controls.MethodsVideopolysomnography (vPSG) was available in 158 newly diagnosed, unmedicated patients with PD and 110 age-, sex-, and education-matched healthy controls (HC). Rapid eye movement (REM) sleep was analyzed for REM without atonia (RWA) and studied by review of time-synchronized video. Motor behaviors and/or vocalizations in REM sleep with a purposeful component other than comfort moves were identified as REM sleep behavioral events (RBE). Two or more events had to be present to be classified as "RBE positive." RBE subjects included rapid eye movement sleep behavior disorder (RBD) and non-RBD subjects based on the presence or absence of RWA > 18.2%.ResultsRBE were detected in 81 of 158 patients with de novo PD (51%) and 17 of 110 HC (15%) (P < 0.001). RBD was identified in 40/81 RBE-positive patients with PD (25% of all PD patients) and 2 of 17 RBE-positive HC (2% of all controls). RBE-positive patients showed no specific motor or neuropsychological features compared to RBE-negative patients. Patients with PD and HC with RBE had more REM sleep (P = 0.002) and a higher periodic leg movements in sleep index (P = 0.022) compared to subjects without RBE.ConclusionThis first description of REM sleep behavioral events (RBE) shows it occurs more frequently in patients with de novo Parkinson disease (PD) than in healthy controls and may be an early sign of neurodegeneration and precede rapid eye movement sleep behavior disorder (RBD). There is no specific phenotype of PD associated with newly defined RBE or RBD at this early stage.
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Project description:BACKGROUND:Short and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal. METHODS:We conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N?=?395?803) and summary statistics from the International Genomics of Alzheimer's Project (N cases/controls?=?17?008/37?154) to investigate the potential impact of sleep duration on cognitive outcomes. RESULTS:Linear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI)?=?0-2%; P?=?0.008] slower reaction time and 3% more errors in visual-memory test (95% CI?=?0-6%; P?=?0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep?=?1.10 (95% CI?=?0.76-1.57); P?=?0.62], decline in reaction time [OR?=?1.28 (95% CI?=?0.49-3.35); P?=?0.61], all-cause dementia [OR?=?1.19 (95% CI?=?0.65-2.19); P?=?0.57] or Alzheimer's disease risk [OR?=?0.89 (95% CI?=?0.67-1.18); P?=?0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity?=?3.44e-9) and reaction time (P for non-linearity?=?6.66e-16). CONCLUSIONS:Linear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition.
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Project description:ImportanceIn the United States, 16 million family caregivers provide long-term care for patients with dementia. Although one's physical, mental, and cognitive health depends on sleep, many caregivers experience chronic stress, and stress is typically associated with worse sleep quantity and quality.ObjectiveTo quantify the extent, nature, and treatability of sleep problems in dementia caregivers.Data sourcesPubMed and Scopus databases were systematically searched for articles published through June 2018 using the following keywords: caregiver or spouse or caretaker AND sleep or circadian AND dementia or Alzheimer. Backward citation tracking was performed, and corresponding authors were contacted for additional data to conduct meta-analyses and pooled analyses.Study selectionTwo reviewers independently screened 805 studies to identify those that reported sleep duration or sleep quality in caregivers of patients with dementia.Data extraction and synthesisFollowing the PRISMA guidelines, 2 reviewers independently extracted data from all studies and conducted National Heart, Lung, and Blood Institute study quality assessments. Meta-analyses with random-effects models were performed to evaluate sleep duration, sleep quality, and sleep interventions in dementia caregivers.Main outcomes and measuresSleep quality and total sleep time were measured by polysomnography, actigraphy, and self-report.ResultsThirty-five studies were analyzed with data from 3268 caregivers (pooled mean age [SD of sample means], 63.48 [5.99] years; 76.7% female) were analyzed. Relative to age-matched control noncaregiver adults, caregivers had lower sleep durations akin to losing 2.42 to 3.50 hours each week (Hedges g?=?-0.29; 95% CI, -0.48 to -0.09; P?=?.01). Sleep quality was significantly lower in caregivers (Hedges g?=?-0.66; 95% CI, -0.89 to -0.42; P?<?.001), but caregivers who underwent sleep intervention trials had better sleep quality than caregivers who did not receive a sleep intervention (Hedges g?=?0.35; 95% CI, 0.20-0.49; P?<?.001).Conclusions and relevanceSleep debt is known to have cumulative associations with physical, mental, and cognitive health; therefore, poor sleep quality in dementia caregivers should be recognized and addressed. Although the caregiving role is stressful and cognitively demanding by its nature, better sleep quality was observed in caregivers who received low-cost behavioral interventions.
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