![]() ![]() DTI studies have offered evidence that white matter microstructure mediates age-related variability in visuospatial function, reasoning, executive function, and perceptual speed, but not in memory, verbal fluency or global cognitive function. Such findings have prompted theories that cortical disconnection drives cognitive aging, yet whether neuroanatomical changes lie along a causal pathway from aging to cognitive decline has been debated. Diffusion tensor imaging (DTI) studies, which allow inference of tissue microstructure from the magnitude and orientation of water diffusion, have identified regionally non-specific decreases in fiber fractional anisotropy (FA) and increases in mean diffusivity (MD) that correspond with age-related decline in these cognitive functions. Leveraging advanced in vivo imaging tools to identify patterns of cytoarchitectural injury that underlie cognitive decline will enhance our understanding of typical brain aging, ultimately helping to disentangle markers of normal from pathological cognitive deficits, and to guide interventions to preserve cognitive health through the end of life.įluid cognitive functions, notably in the executive and memory domains, are most vulnerable to age-related decline, with relative sparing of crystallized knowledge. However, histological studies capable of visualizing cellular morphometry cannot capture changes in the healthy living brain or link structural changes with functional outcomes. Postmortem studies have demonstrated characteristic cytoarchitectural features of the aged brain, including lower dendritic and axonal density, demyelination, and reduced dendritic branching. While cognitive decline may be an inherent consequence of dysfunctional senescent cells, environmental and lifestyle factors may compound basal rates of cell damage, leading trajectories of neuroanatomical change to diverge from those expected for chronological age. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.Įven in the absence of dementia, advancing age is accompanied by variable rates of cognitive decline, posing substantial challenges to defining normal cognitive aging and identifying its neurobiological substrates. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). ![]() Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. ![]()
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