Association of Sleep Disturbances and Cognitive Decline among Cognitively Normal Elders Over Time

Abstract Background: While sleep disturbances (SD) has been shown to be associated with worse cognition, but the causal relationship between the two subjects to debate. Our objective was to investigate the longitudinal impact of SD on cognitive function.Objective: To determine the effect of self-reported clinical diagnosis of SD on longitudinal changes in brain amyloid-PET, CSF-biomarkers (Aβ42, T-tau and P-tau) and cognitive function in cognitively normal.Methods: A total of 463 cognitively normal elders (357 normal and 106 SD) were included. Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants were collected from 2005 to 2020. The generalized linear mixed models adjusting variables which were selected by the Akaike Information Criterion (AIC) and the marginal effect estimation method was used to estimate the risk effect of SD. Cox proportional hazards regression models estimated the relative hazard of Alzheimer’s Disease (AD), among baseline SD patients.Results: The age range of participants was 73.60±5.71 years old, and the female proportion was 43.63%. In adjusted regression models, Participants with baseline SD had higher likelihood of developing worse cognition over subsequent follow-up, PACC (decrease 7.53 points [95%CI, 7.36-7.70]; P<0.001), MMSE (decrease 5.26 points [95%CI, 5.17-5.35]; P<0.001), and CDR–Sum of Boxes (increase 5.61 points [95%CI, 5.67-5.54]; P=0.001). Similarly, Cox regression analysis suggested that sleep disturbances is a risk factor of AD (HR=1.55, 95% CI=1.08 to 2.22).Conclusion: SD probably is a warning sign of AD, because it is associated with greater likelihood of cognitive decline or dementia over time. Associations are likely multifactorial and could be explained by intervening variables in the path from SD to dementia, or by common risk factors for pathological processes in brain. These findings suggest need for more attentions of older adults with sleep compromise.