Sleep and circadian measures at age 73 are related to brain macrostructure, microstructure, and amyloid pathology

Abstract

AbstractBackgroundSleep disturbance is associated with an increased risk of developing Alzheimer’s disease, yet the relationship between sleep metrics and brain pathology remains poorly understood. Complementing ‘traditional’ metrics such as total sleep time (TST) and sleep efficiency (SE), the midpoint of sleep, interdaily stability and intradaily variability provide important insights into chronotype and circadian rest activity rhythms.MethodsWe used data from dementia‐free participants from the Insight 46 neuroscience sub‐study of the MRC National Survey of Health and Development (NSHD, British 1946 Birth Cohort). Hippocampal, whole brain, and white matter hyperintensity volume (WMHV), and amyloid status (positive/negative) were derived from volumetric T1 and FLAIR MRI, and 18F‐florbetapir amyloid‐PET at age 73. TST, SE, midpoint of sleep, interdaily stability, and intradaily variability were calculated from 6 nights of wrist actigraphy (Philips Actiwatch) at the same time point. Normal appearing white matter (NAWM) microstructure was assessed by diffusion weighted imaging at age 70. Mean z‐scores for each participant’s neurite density index (NDI) and orientation dispersion index (ODI) were generated relative to normal controls.The relationship between sleep and imaging metrics was examined using generalised additive models to allow a flexible functional form for the sleep metrics. Where there was no evidence of a nonlinear effect, results are presented from linear regression (continuous outcomes) or logistic regression (binary outcomes). All analyses were controlled for TST, SE, age, gender, socioeconomic status, intracranial volume, and interval from imaging to actigraphy, in addition to blood pressure age 53, and body mass index for WMHV analyses.ResultsThere was a significant nonlinear relationship between TST and both hippocampal and brain volume, with ∼ 7 hours sleep appearing optimal (Table 1, Figure 1). Increasing TST and decreasing SE were associated with decreased NDI. Unexpectedly, increased interdaily stability was associated with an increased risk of being amyloid positive (P = 0.003, Figure 2).ConclusionSleep and circadian measures at age 73 were associated with brain microstructure, macrostructure, and amyloid pathology. Efficient sleep of around 7 hours is associated with optimal brain health. Ongoing longitudinal follow‐up will help to explore causality.