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Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer\u2019s disease change with age, a greater understanding of how the relationship between sleep and cognition changes over time is needed. In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity.<\/jats:p>\n                  <jats:p>To test this hypothesis, we monitored sleep-wake activity over 4\u20136 nights in 100 participants who underwent standardized cognitive testing longitudinally, APOE genotyping, and measurement of Alzheimer\u2019s disease biomarkers, total tau and amyloid-\u03b242 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cued Selective Reminding test, the Logical Memory Delayed Recall assessment, the Digit Symbol Substitution test and the Mini-Mental State Examination. Performance on each of these four tests was Z-scored within the cohort and averaged to calculate a preclinical Alzheimer cognitive composite score. We estimated the effect of cross-sectional sleep parameters on longitudinal cognitive performance using generalized additive mixed effects models. Generalized additive models allow for non-parametric and non-linear model fitting and are simply generalized linear mixed effects models; however, the linear predictors are not constant values but rather a sum of spline fits.<\/jats:p>\n                  <jats:p>We found that longitudinal changes in cognitive function measured by the cognitive composite decreased at low and high values of total sleep time (P\u2009&amp;lt;\u20090.001), time in non-REM (P\u2009&amp;lt;\u20090.001) and REM sleep (P\u2009&amp;lt;\u20090.001), sleep efficiency (P\u2009&amp;lt;\u20090.01) and &amp;lt;1\u2009Hz and 1\u20134.5\u2009Hz non-REM slow wave activity (P\u2009&amp;lt;\u20090.001) even after adjusting for age, CSF total tau\/amyloid-\u03b242 ratio, APOE \u03b54 carrier status, years of education and sex. Cognitive function was stable over time within a middle range of total sleep time, time in non-REM and REM sleep and &amp;lt;1\u2009Hz slow wave activity, suggesting that certain levels of sleep are important for maintaining cognitive function.<\/jats:p>\n                  <jats:p>Although longitudinal and interventional studies are needed, diagnosing and treating sleep disturbances to optimize sleep time and slow wave activity may have a stabilizing effect on cognition in preclinical or early symptomatic Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awab272","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T07:16:51Z","timestamp":1626333411000},"page":"2852-2862","source":"Crossref","is-referenced-by-count":165,"title":["Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-825X","authenticated-orcid":false,"given":"Brendan P","family":"Lucey","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"},{"name":"Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Wisch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7107-3651","authenticated-orcid":false,"given":"Anna H","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C","family":"Landsness","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina D","family":"Toedebusch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S","family":"McLeland","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar H","family":"Butt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Hassenstab","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"},{"name":"Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA"},{"name":"Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA"},{"name":"Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, USA"},{"name":"Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, 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