Sleep Patterns and Prospective Diffusion Weighted Imaging Biomarkers: the Sleep and Dementia Consortium (SDC)

Abstract

AbstractBackgroundAdequate sleep is necessary to maintain brain health, with sleep disturbances associated with higher Alzheimer’s disease (AD) risk. Diffusion‐weighted imaging (DWI) metrics are increasingly recognized as useful neuroimaging biomarkers to detect AD‐related white matter degeneration. We assessed the relationship between sleep patterns and prospective DWI metrics in the Sleep and Dementia Consortium (SDC). The SDC studies associations between polysomnography (PSG)‐derived sleep with dementia risk and cognitive and MRI endophenotypes.MethodThe SDC includes five community‐based cohorts, two of which have DWI acquisitions: The Framingham Heart Study (FHS) and the Atherosclerosis Risk in Communities study (ARIC). Dementia‐free participants who underwent both PSG and DWI‐MRI were selected, including 354 FHS participants (56.6±7.1y, 57%W), and 184 ARIC participants (61.6±5.0y, 52%W). The MRI session was approximately 15 years after the PSG on average (FHS:17.0±1.3y; ARIC:15.8±0.8y). Fractional anisotropy (FA) and mean diffusivity (MD) were considered for both cohorts, in addition to free‐water (FW) in the FHS. Sleep metrics were harmonized centrally, distributed for cohort‐specific linear regressions, and study‐level estimates were pooled in random effects meta‐analyses. Analyses were adjusted for demographics, obesity, time between PSG and MRI, antidepressants and sedative medication usage. An interaction term by APOE4 allele carrier status in regression models was used to test its moderating effect.ResultIn the FHS, sleep fragmentation was associated with DWI measures in the expected direction: Higher Wake After Sleep Onset and lower Sleep Maintenance Efficiency were associated with lower FA (β±SE = ‐0.17±0.09,p = 0.04; β±SE = 0.23±0.10,p = 0.03), higher MD (β±SE = 0.15±0.07,p = 0.04; β±SE = ‐0.20±0.09,p = 0.03), and higher FW (β±SE = 0.17±0.07,p = 0.02; β±SE = ‐0.22±0.08,p = 0.008). Meta‐analysis of FHS and ARIC revealed significant pooled effects between lower Sleep Maintenance Efficiency and lower FA (β±SE = 0.17±0.08,p = 0.04). In the FHS, APOE4 allele significantly moderated the association between REM sleep proportion with FA and MD, where lower REM sleep percentage was associated with higher MD (β±SE = ‐4.89±1.95,p = 0.02) and lower FA (β±SE = 4.93±2.26,p = 0.03) in APOE4 carriers only.ConclusionIn the SDC, sleep fragmentation was associated with MRI markers of poorer white matter integrity 15 years later. Less REM sleep was associated with poorer white matter integrity in APOE4 allele carriers only, suggesting that disrupted sleep architecture may contribute and interact with neurodegenerative processes to affect brain integrity.