Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults

Abstract

Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

Subjective Well-Being and Bilateral Anterior Insula Functional Connectivity After Exercise Intervention in Older Adults With Mild Cognitive Impairment

“…Our results also suggest that the increase in FC between the anterior insula and precuneus may be an important neural basis for the ET-induced enhancements in subjective well-being among older adults diagnosed with MCI. Consistent with our previous studies using the same MCI cohort that showed the ET-related effects were evident in the insula ( Chirles et al, 2017 ; Alfini et al, 2019 ; Callow et al, 2021 ), our work collectively suggests that the insula is a brain region that is particularly impacted by ET in individuals with MCI. While most MCI studies have focused on improvement in cognitive function, the present study extends the existing literature by suggesting that the neuroprotective effects induced by exercise may be extended to the psychological well-being of older adults with MCI.…”

Microstructural and functional plasticity following repeated brain stimulation during cognitive training in non-demented older adults

“…We observed decreased MD after anodal compared to sham group for individuals with initially lower MD in the stimulation target, possibly indicating increases in tissue density (due to reshaping of neuronal or glial processes) or enhanced tissue organization (due to strengthened dendrites or axons) due to tDCS 5,41 . Numerically, MD values suggested a slight increase from before to after the intervention, similar to what has been observed after exersice training in older adults: For example, Callow and colleagues found increases in cortical grey matter (insular) MD after training 42 . These training-induced MD increases were interpreted as reduced in ammation and cellular swelling in the aged brain 43,44 .…”

Inter- and intra-individual variation in brain structural-cognition relationships in aging

“…This suggests that including both structural and diffusion MRI measures increased our sensitivity to complementary underlying structural alterations. While the complexities of DWI underpinnings in grey matter remain as discussed above, our findings support a growing body of literature which demonstrates the utility of cortical DWI measurements to capture age- and cognitive-related variance ( Callow et al, 2021 ; Grydeland et al, 2013 ; Philippi et al, 2016 ; Radhakrishnan et al, 2022 ; Raz & Rodrigue, 2006 ; Reas et al, 2018 ; Rodriguez-Vieitez et al, 2021 ; Schneider et al, 2019 ). We also note that across all components identified as contributing to brain-cognition relationships, DWI metrics displayed a complementary nature.…”