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Objective: To test the hypothesis that worse self-reported sleep relates to reduced hippocampal integrity as indexed by increased intra-hippocampal water diffusion, and that this relationship is stronger in the presence of β-amyloid (Aβ) accumulation, a marker of Alzheimer’s disease (AD) pathology. Methods. Two-hundred and fifty-one participants, aged 19-81 years, completed the Pittsburgh Sleep Quality Index, and 2 diffusion tensor imaging sessions, on average 3 years apart, allowing estimates of decline in hippocampal microstructural integrity as indexed by increased mean diffusivity (MD). We used the delayed recall from the California Verbal Learning Test to measure memory change. 18F-Flutemetamol PET, in 108 participants above 44 years of age, yielded 23 Aβ positive cases. Genotyping enabled controlling for APOE ε4 status, and polygenic scores for sleep efficiency and AD. Results. Worse global sleep quality and sleep efficiency related to more rapid reduction in hippocampal microstructural integrity over time. Focusing on sleep efficiency, this relationship was stronger in presence of cortical Aβ accumulation. Sleep efficiency also related to memory decline indirectly via hippocampal integrity decline. The results were not explained by genetic risk for sleep efficiency and AD. Conclusions. Poor self-reported sleep efficiency related to decline in hippocampal integrity, especially in the presence of Aβ accumulation. Poor sleep and hippocampal microstructural decline may partly explain memory decline in older adults with Aβ pathology. The relationships were not explained by genetic risk, and poor self- reported sleep efficiency might constitute a risk factor for AD, although the causal mechanisms driving the of observed associations are unknown.

Original publication




Journal article




Coldspring Harbor Laboratory

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