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      Excessive Sleepiness and Longer Nighttime in Bed Increase the Risk of Cognitive Decline in Frail Elderly Subjects: The MAPT-Sleep Study

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          Abstract

          Objective: To identify self-reported sleep-wake disturbances that increase the risk of cognitive decline over 1-year follow-up in frail participants.

          Background: Risk factors for cognitive impairment need to be better identified especially at earliest stages of the pathogenesis. Sleep-wake disturbances may be critical factors to consider and were thus being assessed in this at-risk population for cognitive decline.

          Methods: Frail elderly participants aged ≥70 years were selected from a subsample of the Multi-domain Alzheimer Preventive Trial (MAPT) for a sleep assessment (MAPT-sleep study) at 18-month follow-up (M18). Sleep-wake disturbances were evaluated using a clinical interview (duration of daytime and nighttime sleep, time in bed, number of naps, and presence of clinically-defined sleep disorders) and numerous validated questionnaires [Epworth Sleepiness Scale for excessive daytime sleepiness (EDS), Insomnia Severity Scale and Berlin Questionnaire]. Cognitive decline was defined as a difference between the MMSE and cognitive composite scores at M24 and M36 that was ranked in the lowest decile. Multivariate logistic regression models adjusted for several potential confounding factors were performed.

          Results: Among the 479 frail participants, 63 developed MMSE-cognitive decline and 50 cognitive composite score decrease between M24 and M36. Subjects with EDS had an increased risk of MMSE decline (OR = 2.46; 95% CI [1.28; 4.71], p = 0.007). A longer time spent in bed during night was associated with cognitive composite score decline (OR = 1.32 [1.03; 1.71], p = 0.03). These associations persisted when controlling for potential confounders. Patients with MMSE score decline and EDS had more naps, clinically-defined REM-sleep Behavior Disorder, fatigue and insomnia symptoms, while patients with cognitive composite score decline with longer time in bed had increased 24-h total sleep time duration but with higher wake time after onset.

          Conclusions: The risk of cognitive decline is higher in frailty subjects with EDS and longer nighttime in bed. Early detection of sleep-wake disturbances might help identifying frail subjects at risk of cognitive decline to further propose sleep health strategies to prevent cognitive impairment.

          http://www.clinicaltrials.gov NCT00672685; Date of registration May, 2nd 2008.

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          What sleep characteristics predict cognitive decline in the elderly?

          Hannah Amy Dianne Keage, Siobhan Banks, Kit Yang … (2012)
          Sleep is critical for optimal cognitive function, but as we age both cognitive impairment and sleep problems increase. Longitudinal, population-based studies can be used to investigate temporal relationships between sleep and cognition. A total of 2012 cognitively unimpaired individuals 65 years and over were drawn from the MRC Cognitive Function and Ageing Study (CFAS). They answered self-reported measures including: insomnia symptoms and age of onset, night time wakings, snoring, sleep onset latency, napping, daytime sleepiness and duration of night time sleep. Cognition was measured via the Mini-Mental State Examination. It was found that daytime napping at baseline was associated with a lower risk of cognitive decline at two and 10 years, and that obtaining ≤6.5h of night-time sleep and excessive daytime sleepiness at baseline were associated with an increased risk at 10 years. Daytime napping, night-time sleep duration, and excessive daytime sleepiness may be modifiable behaviours open to intervention strategies, or, clinical indicators of future decline in older individuals. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.
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            The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women.

            Shelley S. Tworoger, Sunmin Lee, Eva Schernhammer … (2015)
            We examined the association of sleep duration, snoring, and difficulty sleeping with cognitive function in a cohort of community-dwelling women. Women (n = 1844), aged 70 to 81 years at initial cognitive interview in 2000, are members of the Nurses' Health Study cohort. Women completed six tests of cognitive function encompassing general cognition, verbal memory, category fluency, and attention. We repeated the assessment 2 years later. We used linear regression models to obtain multivariate-adjusted mean differences in initial test performance, and in cognitive decline over time, across categories of sleep duration (< or =5,6,7,8,9+ hours/night), frequency of snoring (never, occasionally, regularly), and sleep difficulties (rarely/never, occasionally, regularly). In analyses of initial test performance, women sleeping < or =5 hours/night scored worse than women sleeping 7 hours/night (mean difference on global score combining all cognitive tests = 0.15 standard units, 95% CI: -0.28, -0.02). Women who regularly had difficulty falling or staying asleep scored 0.11 units lower on the global score (95% CI: -0.22, 0.01) compared with those who rarely had difficulty sleeping. These differences were equivalent to the mean differences in score observed between participants who were 4 to 5 years apart in age. We found no associations with snoring or with any of the sleep variables and cognitive decline over 2 years. Associations between sleep patterns and initial cognitive function may be clinically relevant given that diminished cognition is a risk factor for dementia. However, the lack of an association with prospective cognitive decline warrants further investigation.
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              Insomnia and daytime sleepiness are risk factors for depressive symptoms in the elderly.

              Isabelle Jaussent, Jean Bouyer, Marie-Laure Ancelin … (2011)
              Previous studies have reported that insomnia and excessive daytime sleepiness (EDS) may predict depression in adults. However, these associations have not been investigated in community-dwelling elderly taking into account insomnia symptoms, EDS, and sleep medication. Four-year longitudinal study. The French Three-City Study. 3824 subjects aged ≥ 65 years and free of depressive symptoms at baseline. Questionnaires were used to evaluate "insomnia symptoms", EDS, and sleep medication at baseline. Depressive symptoms (DEP-s) were assessed using the Center for Epidemiologic Studies-Depression scale at baseline, and at 2-year and 4-year follow-up. Logistic regression models controlling for potential confounders were generated to determine whether sleep disturbances were associated with incident DEP-s and to determine the effect of individual insomnia symptoms. Insomnia symptoms and EDS independently increased the risk of incident DEP-s (OR=1.23, 95% CI=1.01-1.49 and OR=2.05, 95% CI=1.30-3.23, respectively). Poor sleep quality and difficulty in initiating and in maintaining sleep-but not early morning awakening-were identified as risk factors of DEP-s, with risk increasing with the frequency of insomnia symptoms. Sleep medication was not only a risk factor for DEP-s independent of insomnia symptoms (OR=1.62, 95% CI=1.26-2.09), but also independent of EDS (OR=1.71 95%=1.33-2.20). Insomnia symptoms, EDS, and the use of medication independently increase the risk of subsequent depression in the elderly. In clinical practice, disturbed sleep and prolonged use of sleep medication may be early indicators or potentially reversible risk factors for depression, suggesting the need for further clinical interventional research.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Aging Neurosci
                Journal ID (iso-abbrev): Front Aging Neurosci
                Journal ID (publisher-id): Front. Aging Neurosci.
                Title: Frontiers in Aging Neuroscience
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1663-4365
                Publication date (Electronic): 28 September 2017
                Publication date Collection: 2017
                Volume: 9
                Electronic Location Identifier: 312
                Affiliations
                [1] 1Department of Neurology, Memory Research and Resources Center, CHU Montpellier , Montpellier, France
                [2] 2University of Montpellier , Montpellier, France
                [3] 3Institut National de la Santé et de la Recherche Médicale U 1183, Saint Eloi Hospital , Montpellier, France
                [4] 4Institut National de la Santé et de la Recherche Médicale U 1061, La Colombière Hospital , Montpellier, France
                [5] 5Department of Psychiatry, Memory Research and Resources Center, CHU Nice , Nice, France
                [6] 6Gérontopôle de Toulouse, Institut National de la Santé et de la Recherche Médicale UMR1027, Toulouse Université III , Toulouse, France
                [7] 7Department of Neurology, Narcolepsy National Reference Center, Sleep Center, CHU Montpellier, University of Montpellier , Montpellier, France
                Author notes

                Edited by: Catarina Oliveira, University of Coimbra, Portugal

                Reviewed by: Agnes Lacreuse, University of Massachusetts Amherst, United States; Masoud Tahmasian, Shahid Beheshti University, Iran

                *Correspondence: Audrey Gabelle a-gabelle@ 123456chu-montpellier.fr

                †The members of the MAPT/DSA group are listed in Section Members of the MAPT/DSA Group.

                Article
                DOI: 10.3389/fnagi.2017.00312
                PMC ID: 5625324
                PubMed ID: 29033827
                SO-VID: 0e539bf2-ebac-47cc-a62c-647ced272757
                Copyright © Copyright © 2017 Gabelle, Gutierrez, Jaussent, Navucet, Grasselli, Bennys, Marelli, David, Andrieu, Berr, Vellas and Dauvilliers on behalf of the MAPT/DSA Study Group.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 15 March 2017
                Date accepted : 12 September 2017
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 38, Pages: 11, Words: 8014
                Categories
                Subject: Neuroscience
                Subject: Original Research

                ScienceOpen disciplines: Neurosciences
                Keywords: sleep,alzheimer disease,cognitive decline,frailty and cognitive impairment,excessive daytime sleepiness,amyloid
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: sleep, alzheimer disease, cognitive decline, frailty and cognitive impairment, excessive daytime sleepiness, amyloid

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