Abstract
ObjectiveTo test whether postmortem MRI captures brain tissue characteristics that mediate the association between physical activity and cognition in older adults.MethodsParticipants (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.ResultsTwo 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.ConclusionThe 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.
Highlights
In the absence of treatments to prevent or reduce the symptoms of Alzheimer’s and other forms of related dementia, intensified efforts are underway to identify modifiable lifestyle behaviors that help to preserve cognition in older adults [1,2]
This view draws support from animal [9,10] and human studies [11,12] showing that higher levels of habitual physical activity are linked to better white matter integrity on MRI, combined with complementary investigations showing that MR-visible white matter abnormalities are in turn related to impaired cognition [13,14]
We used clinical and postmortem data collected in the Rush Memory and Aging Project (MAP), a community-based cohort study of older adults, to examine whether the transverse relaxation rate R2, an MRI index related to brain tissue microstructure, mediates the relation between physical activity and cognition in old age
Summary
In the absence of treatments to prevent or reduce the symptoms of Alzheimer’s and other forms of related dementia, intensified efforts are underway to identify modifiable lifestyle behaviors that help to preserve cognition in older adults [1,2]. The neurobiologic basis of these associations remains incompletely understood, as underscored by our recent work showing that physical activity and cognition are not linked via indices of brain pathologies that are common among older adults [7] This knowledge gap has impeded the translation of findings from observational studies into effective activity-based interventions against cognitive decline, highlighting the importance of identifying factors other than traditional histopathologic indices of brain pathologies that may connect physical activity and cognition. Adding further support for white matter microstructure as a potential physiologic mediator of the relation between physical activity and cognition are studies showing that MRI metrics of white matter microstructure and connectivity are related to established correlates of resilience to cognitive decline such as intelligence and to resilience itself [15,16].
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