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Sex differences in associations between brain microstructure and cognitive aging
Author(s) -
Reas Emilie T,
Hagler Donald J,
Lee Ronald R,
Dale Anders M,
McEvoy Linda K
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047459
Subject(s) - cognition , cognitive decline , psychology , effects of sleep deprivation on cognitive performance , white matter , brain aging , brain structure and function , diffusion mri , medicine , dementia , neuroscience , disease , magnetic resonance imaging , radiology
Background Cytoarchitectural brain changes during normal aging remain poorly characterized, with further uncertainty whether patterns of brain aging underlying cognitive dysfunction differ by sex. Prior studies have demonstrated that the diffusion MRI technique restriction spectrum imaging (RSI) predicts cognitive decline and pathology in Alzheimer’s disease (Reas et al., 2017,2018,2019), but sensitivity of RSI to typical brain aging has not been assessed. Method This study used RSI to examine sex differences in associations of brain microstructure with age and cognition in community‐dwelling participants of the Rancho Bernardo Study. Ninety women and 57 men aged 56‐99 completed RSI and cognitive assessment (global cognitive function, executive function, verbal memory, visual memory, logical memory). RSI metrics of restricted, hindered, and free water diffusion were computed in cortical gray matter, hippocampus, and white matter fibers. Sex‐specific correlations assessed associations of RSI with age and with cognitive function. Mediation analyses examined whether RSI measures mediated effects of age on cognitive performance. Result Age‐related increases in free water, and decreases in measures thought to reflect intraneurite (restricted) and extraneurite (hindered) diffusion, and neurite complexity, were observed throughout gray matter and fibers. Associations remained after adjusting for cortical thinning, and regional associations emerged after adjustment for global microstructure. Associations of microstructure with age and with cognitive function were stronger and more widespread for women than men. Adjustment for age attenuated RSI‐cognition correlations for both sexes, as well as sex differences in these associations. Microstructure partially mediated effects of age on cognitive performance for men and women. Whereas age more strongly correlated with RSI and cognitive measures for women, RSI measures more strongly mediated age effects on cognitive function for men. Conclusion Microstructural brain changes, which may reflect cell shrinkage, demyelination, axonal and dendritic loss, or reduced neurite complexity, occur with typical aging and correlate with performance in multiple cognitive domains. Age‐related microstructural injury is more pronounced for women, and patterns by which microstructure mediates cognitive aging differ by sex. Normal aging may be accompanied by cytoarchitectural damage that underlies cognitive decline, and the mechanisms by which age‐related neural injury impairs cognitive function may differ between men and women.