Association of Sleep Disturbances With Longitudinal Cognitive Decline Among Cognitively Normal Elders

Abstract Background: A lot of evidence demonstrated sleep disturbances (SD) gets associated with Alzheimer’s disease (AD), but whether or not sleep disturbances could be the preclinical stage of AD is still unknown.Objective: 463 cognitively normal elders (357 normal and 106 SD) in baseline with cognitive and biomarker data were included in the study. Participants were collected from 2005 to 2020 (16 years follow-up) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The generalized linear mixed models adjusting variables selected by the Akaike Information Criterion (AIC) and the marginal effect estimation method were used to estimate the effect of SD for cognition. Moreover, Cox regression was used to assess the survival risk of AD in sleep disturbance.Results: The age range of participants was 73.60±5.71 years old, and the female proportion was 43.63%. Compared with the group with normal sleep, those with sleep disturbances had worse mean scores at 6 years on the PACC (mean difference, 7.53 points [95%CI, 7.36-7.70]; P<0.001), MMSE (mean difference, 5.26 points [95%CI, 5.17-5.35]; P<0.001), and CDR–Sum of Boxes (mean difference, 5.61 points [95%CI, 5.67-5.54]; P = 0.001). Cox regression analysis suggested that sleep disturbances is a risk factor of AD (HR=1.55, 95% CI=1.08 to 2.22).Conclusion: Research of a cognitively normal cohort followed up for a mean of 9.56 years suggest that sleep disturbances, compared with normal sleep status, was associated with higher likelihood cognitive, which means sleep disturbances could probably be the pre-symptomatic stage of AD.