Abstract
Study ObjectivesA critical role linking sleep with memory decay and β-amyloid (Aβ) accumulation, two markers of Alzheimer’s disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of Aβ.MethodsTwo-hundred and forty-three cognitively healthy participants, aged 19–81 years, completed the Pittsburgh Sleep Quality Index once, and two diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 Aβ positive. Genotyping enabled control for APOE ε4 status, and polygenic scores for sleep and AD, respectively.ResultsWorse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of Aβ accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD.ConclusionsWorse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of Aβ accumulation, and Aβ might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown.
Highlights
Individuals with sleep disturbances have increased risk for Alzheimer’s disease (AD) [1], and accumulation of β-amyloid (Aβ) [2, 3]
Taken together, testing whether worse self-reported sleep relates to memory decline and more rapid reduction of hippocampal integrity while controlling for genetic variation in both sleep and AD, and whether such relations are stronger in older adults with pathological levels of Aβ, might aid in the quest to decipher the role of sleep problems in early AD-related pathology
The results indicate that sleep efficiency and hippocampal microstructural decline are related in presence of cortical Aβ accumulation
Summary
For each participant, we registered the static PET image to the anatomical T1-weighted image using boundary-based registration [38] This registration was inverted to get a high-resolution segmentation (upsample factor = 2) from the high-resolution MRI space in PET space, and simultaneously perform the partial volume correction with the Symmetric Geometric Transfer Matrix method, as recommended when using regions of interests (instead of vertex-wise) approach [51, 52]. As a proxy measure of head movement during scanning, we calculated temporal signal-tonoise ratio from the diffusion scans [67], which increased with age (R2=.40, p < .001) We included this ratio in all hippocampal MD analyses as covariate of no interest, in addition to hippocampal volume at baseline MRI, and difference in movement and hippocampal volume between baseline and follow-up MRI. We excluded the 11 participants with high depression scores, and the two participants with a low MMS score, and assessed the similarities with the main results
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