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Cardiorespiratory Fitness Modifies Influence of Sleep Problems on Cerebrospinal Fluid Biomarkers in an At-Risk Cohort

Law, LL; Sprecher, KE; Dougherty, RJ; Edwards, DF; Koscik, RL; Gallagher, CL; Carlsson, CM; ... Okonkwo, OC; + view all (2019) Cardiorespiratory Fitness Modifies Influence of Sleep Problems on Cerebrospinal Fluid Biomarkers in an At-Risk Cohort. Journal of Alzheimer's Disease , 69 (1) pp. 111-121. 10.3233/JAD-180291. Green open access

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Abstract

Background: Previous studies indicate that cardiorespiratory fitness (CRF) and sleep are each favorably associated with Alzheimer’s disease (AD) pathophysiology, including reduced amyloid-β (Aβ) and tau pathology. However, few studies have examined CRF and sleep in the same analysis. Objective: To examine the relationship between sleep and core AD cerebrospinal fluid (CSF) biomarkers among at-risk healthy late-middle-aged adults and determine whether CRF modifies this association. Methods: Seventy-four adults (age = 64.38±5.48, 68.9% female) from the Wisconsin Registry for Alzheimer’s Prevention participated. Sleep was evaluated using the Medical Outcomes Study Sleep Scale, specifically the Sleep Problems Index I (SPI), which incorporates domains of sleep disturbance, somnolence, sleep adequacy, and shortness of breath. Higher scores indicate greater sleep problems. To assess CRF, participants underwent a graded exercise test. CSF was collected via lumbar puncture, from which Aβ42, total-tau (t-tau), and phosphorylated-tau (p-tau) were immunoassayed. Regression analyses examined the association between SPI and CSF biomarkers, and the interaction between SPI and CRF on these same biomarkers, adjusting for relevant covariates. Results: Higher SPI scores were associated with greater p-tau (p = 0.027) and higher t-tau/Aβ42 (p = 0.021) and p-tau/Aβ42 (p = 0.009) ratios. Analyses revealed significant SPI*CRF interactions for t-tau (p = 0.016), p-tau (p = 0.008), and p-tau/Aβ42 (p = 0.041); with a trend for t-tau/Aβ42 (p = 0.061). Specifically, the relationship between poorer sleep and these biomarkers was significant among less fit individuals, but not among those who were more fit. Conclusion: In a late-middle-aged at-risk cohort, CRF attenuated the association between poor sleep and levels of select CSF biomarkers. This suggests fitness may play an important role in preventing AD by protecting against pathology, even in impaired sleep.

Type: Article
Title: Cardiorespiratory Fitness Modifies Influence of Sleep Problems on Cerebrospinal Fluid Biomarkers in an At-Risk Cohort
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-180291
Publisher version: https://doi.org/10.3233/JAD-180291
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer’s disease, amyloid-β protein, biomarkers, cardiorespiratory fitness, cerebrospinal fluid, sleep, tau protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10072864
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