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Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer's Disease.

ABSTRACT: OBJECTIVE:This study explored two research questions: (a) Does sleep medication neutralize or provide a protective effect against the hazard of Alzheimer's disease (AD)? (b) Do apolipoprotein (APOE) e4 carriers reporting a sleep disturbance experience an increased risk of AD? METHOD:This study is a secondary analysis of the National Alzheimer's Coordinating Center's Uniform Data Set ( n = 6,782) using Cox proportional hazards regression. RESULTS:Sleep disturbance was significantly associated with eventual AD development. Among the subset of participants taking general sleep medications, no relationship between sleep disturbance and eventual AD was observed. Among individuals not taking sleep medications, the increased hazard between the two variables remained. Among APOE e4 carriers, sleep disturbance and AD were significant, except among those taking zolpidem. DISCUSSION:Our findings support the emerging link between sleep disturbance and AD. Our findings also suggest a continued need to elucidate the mechanisms that offer protective factors against AD development.

SUBMITTER: Burke SL

PROVIDER: S-EPMC6328323 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer's Disease.

Burke Shanna L SL Hu Tianyan T Spadola Christine E CE Burgess Aaron A Li Tan T Cadet Tamara T

Journal of aging and health 20180830 2

<h4>Objective</h4>This study explored two research questions: (a) Does sleep medication neutralize or provide a protective effect against the hazard of Alzheimer's disease (AD)? (b) Do apolipoprotein (APOE) e4 carriers reporting a sleep disturbance experience an increased risk of AD?<h4>Method</h4>This study is a secondary analysis of the National Alzheimer's Coordinating Center's Uniform Data Set ( n = 6,782) using Cox proportional hazards regression.<h4>Results</h4>Sleep disturbance was signif ...[more]

PMID: 30160576

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Project description:Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1β CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.

Project description:Study objectivesWe evaluated factors associated with the presence of sleep disturbance in patients with stroke and whether sleep disturbance predicted change in other patient-reported domains of health over time.MethodsObservational cohort study of 2,190 patients with stroke seen in a cerebrovascular clinic February 17, 2015 to July 5, 2017 who completed patient-reported outcome measures (PROMs) at ≥ 1 visit, including the Patient Health Questionnaire-9 depression screen, Quality of Life in Neurological Disorders (NeuroQoL) cognitive function and Patient-Reported Outcomes Information Measurement System (PROMIS) sleep disturbance, fatigue, anxiety, social role satisfaction, physical function, and pain interference. Separate multivariable models were constructed with PROMIS sleep disturbance as the dependent variable. Covariates included clinical and demographic variables, the Patient Health Questionnaire-9 depression screen scored on the PROMIS metric, and 1 of the 6 other PROMs. Among the 476 patients with ≥ 2 visits, linear regression models were constructed to determine the association of baseline sleep disturbance with follow-up PROMs after adjustment for the corresponding baseline PROMIS/NeuroQol scores, depression score, and clinical variables.ResultsYounger age and all PROM scores were associated with sleep disturbance; depression had the greatest association among PROMs (beta estimate 0.53, 95% confidence interval, 0.49, 0.57), physical function had the least (-0.06, 95% confidence interval, -0.11, -0.01). Baseline PROMIS sleep disturbance score was associated with worse adjusted follow-up scores for depression, fatigue, social role satisfaction, and physical function.ConclusionsYounger age and all 8 PROMs were associated with sleep disturbance in patients with stroke. The degree of sleep disturbance predicted future patient-reported outcomes for multiple domains of health. Further study is warranted to determine if interventions shown to improve sleep symptoms will also improve other outcomes.

Dataset Information

Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer's Disease.

Publications

Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer's Disease.

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