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Objective To test whether postmortem MRI captures brain tissue characteristics that mediate the association between physical activity and cognition in older adults. Methods Participants (N = 318) were older adults from the Rush Memory and Aging Project who wore a device to quantify physical activity and also underwent detailed cognitive and motor testing. Following death, cerebral hemispheres underwent MRI to quantify the transverse relaxation rate R2, a metric related to tissue microstructure. For analyses, we reduced the dimensionality of the R2 maps from approximately 500,000 voxels to 30 components using spatial independent component analysis (ICA). Via path analysis, we examined whether these R2 components attenuated the association between physical activity and cognition, controlling for motor abilities and indices of common brain pathologies. Results Two of the 30 R2 components were associated with both total daily physical activity and global cognition assessed proximate to death. We visualized these components by highlighting the clusters of voxels whose R2 values contributed most strongly to each. One of these spatial signatures spanned periventricular white matter and hippocampus, while the other encompassed white matter of the occipital lobe. These two R2 components partially mediated the association between physical activity and cognition, accounting for 12.7% of the relationship (p = .01). This mediation remained evident after controlling for motor abilities and neurodegenerative and vascular brain pathologies. Conclusion The association between physically activity and cognition in older adults is partially accounted for by MRI-based signatures of brain tissue microstructure. Further studies are needed to elucidate the molecular mechanisms underlying this pathway.

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being.