TY - JOUR
T1 - Sleep fragmentation, microglial aging, and cognitive impairment in adults with and without Alzheimer’s dementia
AU - Kaneshwaran, Kirusanthy
AU - Olah, Marta
AU - Tasaki, Shinya
AU - Yu, Lei
AU - Bradshaw, Elizabeth M.
AU - Schneider, Julie A.
AU - Buchman, Aron S.
AU - Bennett, David A.
AU - de Jager, Philip L.
AU - Lim, Andrew S.P.
N1 - Funding Information:
We acknowledge the participants in the ROS and MAP cohorts and their families. Funding: This study was funded by the NIH (www.nih.gov) (grants R01AG052488, RF1AG036042, U01AG46152, R01AG048015, U01AG061356, P30AG010161, RF1AG15819, R01AG017917, R01AG047976, R01AG056352, R01AG024480, R01NS78009, R01AG042210, UH2NS100599, R01NS089674, and R01AG043617), the Canadian Institutes of Health Research (www.cihr-irsc.gc.ca/) (MOP125934 and MSH136642), the Robert C. Borwell Endowment Fund, and a CREMS studentship from the University of Toronto. Author
Publisher Copyright:
Copyright © 2019 The Authors
PY - 2019/12/11
Y1 - 2019/12/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076681530&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aax7331
DO - 10.1126/sciadv.aax7331
M3 - Article
C2 - 31844665
AN - SCOPUS:85076681530
VL - 5
JO - Science Advances
JF - Science Advances
SN - 2375-2548
IS - 12
M1 - eaax7331
ER -