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However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14\u2009days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (A\u03b242), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12\u2009months of follow-up. Linear regression models were performed considering the global population and A\u03b242+ patients only.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The cohort included 100 patients with mild-moderate AD. The median age [p<jats:sub>25<\/jats:sub>;p<jats:sub>75<\/jats:sub>] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; <jats:italic>p<\/jats:italic> = 0.001) and male sex (0.780 [0.193]; <jats:italic>p<\/jats:italic> = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; <jats:italic>p<\/jats:italic> = 0.001) and NF-L (0.444 [0.212 to 0.676]; <jats:italic>p<\/jats:italic> = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau\/A\u03b242 ratio, educational level, and season of the year (\u2212 0.715 [\u2212 1.272 to \u2212 0.157]; <jats:italic>p<\/jats:italic> = 0.013). Similar findings were obtained considering only the A\u03b242+ patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-021-00903-7","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T16:02:25Z","timestamp":1632585745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The circadian rest-activity pattern predicts cognitive decline among mild-moderate Alzheimer\u2019s disease patients"],"prefix":"10.1186","volume":"13","author":[{"given":"Adriano D. 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