Sleep fragmentation, microglial aging, and cognitive impairment in adults with and without Alzheimer's dementia

Sleep disruption is associated with cognitive decline and dementia in older adults; however, the underlying mechanisms are unclear. In rodents, sleep disruption causes microglial activation, inhibition of which improves cognition. However, data from humans are lacking. We studied participants in two...

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Bibliographic Details
Published in:Science advances 2019-12, Vol.5 (12), p.eaax7331-eaax7331
Main Authors: Kaneshwaran, Kirusanthy, Olah, Marta, Tasaki, Shinya, Yu, Lei, Bradshaw, Elizabeth M, Schneider, Julie A, Buchman, Aron S, Bennett, David A, De Jager, Philip L, Lim, Andrew S P
Format: Article
Language:English
Subjects:
Aged, 80 and over
Aging - genetics
Aging - pathology
Alzheimer Disease - diagnostic imaging
Alzheimer Disease - genetics
Alzheimer Disease - physiopathology
Cognitive Dysfunction - diagnostic imaging
Cognitive Dysfunction - genetics
Cognitive Dysfunction - physiopathology
Dementia - diagnostic imaging
Dementia - genetics
Dementia - physiopathology
Female
Humans
Male
Memory - physiology
Microglia - metabolism
Microglia - pathology
Neuroscience
SciAdv r-articles
Sequence Analysis, RNA
Sleep - genetics
Sleep - physiology
Sleep Deprivation - genetics
Sleep Deprivation - physiopathology
Sleep Wake Disorders - diagnostic imaging
Sleep Wake Disorders - genetics
Sleep Wake Disorders - physiopathology
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Summary:Sleep disruption is associated with cognitive decline and dementia in older adults; however, the underlying mechanisms are unclear. In rodents, sleep disruption causes microglial activation, inhibition of which improves cognition. However, data from humans are lacking. We studied participants in two cohort studies of older persons-the Rush Memory and Aging Project and the Religious Orders Study. We assessed sleep fragmentation by actigraphy and related this to cognitive function, to neocortical microglial marker gene expression measured by RNA sequencing, and to the neocortical density of microglia assessed by immunohistochemistry. Greater sleep fragmentation was associated with higher neocortical expression of genes characteristic of aged microglia, and a higher proportion of morphologically activated microglia, independent of chronological age- and dementia-related neuropathologies. Furthermore, these were, in turn, associated with worse cognition. This suggests that sleep fragmentation is accompanied by accelerated microglial aging and activation, which may partially underlie its association with cognitive impairment.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aax7331