Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

Abstract

Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. Two Framingham Heart Study overlapping samples were studied: participants who underwent ¹¹C-Pittsburg Compound B amyloid and ¹⁸F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7-8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average β [SE] 0.0062 [0.0024], <i>p</i> = 0.009; short to long β [SE] 0.0164 [0.0076], <i>p</i> = 0.031; average to long β [SE] 0.0083 [0.0022], <i>p</i> = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (β [SE] 0.29 [0.11], <i>p</i> = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7-8 hours in fully adjusted models (β [SE] -0.43 [0.20], <i>p</i> = 0.028; β [SE] -0.019 [0.004], <i>p</i> = 0.020). Each hour of increasing sleep (continuous, β [SE] 0.12 [0.04], <i>p</i> = 0.003; β [SE] 0.002 [0.001], <i>p</i> = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; β [SE] 0.24 [0.10], <i>p</i> = 0.019; β [SE] 0.0081 [0.0025], <i>p</i> = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.