Contributions of Gray Matter Microstructure to Differences in Fluid Cognition and Episodic Memory Across the Healthy Adult Lifespan.

Age-related differences in gray matter microstructure were observed across functionally defined networks in healthy adults spanning the adult lifespan.

• Sample consisted of 152 healthy adults aged 18–88 years without cognitive impairment or dementia.
• A multicompartment diffusion-weighted imaging (dMRI) model was used to assess gray matter microstructure.
• Analyses were conducted across functionally defined brain networks rather than individual regions alone.
• The study extended prior white matter-focused dMRI analyses to gray matter tissue using methodological advances in dMRI acquisition and modeling.

Significant nonlinear age-related increases in intracellular diffusion and decreases in dispersed diffusion were observed in gray matter.

• Intracellular diffusion showed nonlinear, age-related increases across gray matter networks.
• Dispersed diffusion showed nonlinear, age-related decreases across gray matter networks.
• These nonlinear patterns were distinct from the pattern observed for free diffusion.
• These alterations represent distinct profiles of gray matter microstructural change across the healthy adult lifespan.

Free diffusion showed linear age-related increases and exhibited the most pronounced age-related effects, especially in frontoparietal relative to occipital regions.

• Linear increases in free diffusion were observed with age in gray matter.
• Free diffusion age-related effects were more pronounced in frontoparietal regions compared to occipital regions.
• Free diffusion exhibited 'the most pronounced age-related effects' among the microstructural measures examined.
• Regional differences in age-related free diffusion changes suggest anterior brain regions are more vulnerable to age-related gray matter microstructural alterations.

Dispersed diffusion in the dorsal attention network statistically mediated age-related differences in episodic memory performance.

• Mediation analysis was conducted to assess whether gray matter microstructural alterations accounted for age-related differences in episodic memory.
• The specific network implicated was the dorsal attention network.
• Dispersed diffusion, not free or intracellular diffusion, was the microstructural metric driving this mediation effect for episodic memory.
• This finding suggests that age-related reductions in dispersed diffusion in the dorsal attention network partially explain age-related episodic memory decline.

Higher intracellular diffusion in the default mode and ventral attention networks was associated with worse fluid cognition performance, but only in adults older than 51 years.

• The relationship between intracellular diffusion and fluid cognition was specific to adults greater than 51 years of age.
• Networks implicated were the default mode network and the ventral attention network.
• Fluid cognition assessed was speed-dependent, reflecting processing speed components.
• This age-moderated relationship suggests that the negative impact of gray matter microstructural alterations on fluid cognition becomes more pronounced after midlife.

Prior studies have primarily linked age-related cognitive decline to white matter tissue alterations, but this study extends such analyses to gray matter using advanced dMRI modeling.

• Methodological advances in dMRI data acquisition and modeling now allow microstructural analyses to be applied to gray matter tissue.
• A multicompartment dMRI model was applied, enabling separation of intracellular, dispersed, and free diffusion compartments in gray matter.
• The study specifically assessed gray matter microstructure of functionally defined networks, a relatively novel approach.
• The authors note that prior work has 'primarily linked age-related cognitive decline to alterations in white matter tissue.'