The effect of vascular health factors on white matter microstructure mediates age-related differences in executive function performance

Abstract

Even within healthy aging, vascular risk factors can detrimentally influence cognition, with executive functions (EF) particularly vulnerable. Fronto-parietal white matter (WM) connectivity in part, supports EF and may be particularly sensitive to vascular risk. Here, we utilized structural equation modeling in 184 healthy adults (aged 20-94 years of age) to test the hypotheses that: 1) fronto-parietal WM microstructure mediates age effects on EF; 2) higher blood pressure (BP) and white matter hyperintensity (WMH) burden influences this association.All participants underwent comprehensive cognitive and neuropsychological testing including tests of processing speed, executive function (with a focus on tasks that require switching and inhibition) and completed an MRI scanning session that included FLAIR imaging for semiautomated quantification of white matter hyperintensity burden and diffusion-weighted imaging for tractography. Structural equation models were specified with age (as a continuous variable) and blood pressure predicting within-tract WMH burden and fractional anisotropy predicting executive function and processing speed. Results indicated that fronto-parietal white matter of the genu of the corpus collosum, superior longitudinal fasciculus, and the inferior frontal occipital fasciculus mediated the association between age and EF. Additionally, increased systolic blood pressure and white matter hyperintensity burden within these white matter tracts contribute to worsening white matter health and are important factors underlying age-brainbehavior associations. These findings suggest that aging brings about increases in both BP and WMH burden, which may be involved in the degradation of white matter connectivity and in turn, negatively impact executive functions as we age.

Early Alzheimer's disease‐like reductions in gray matter and cognitive function with aging in nonhuman primates

“…In human studies, recent work suggests that executive function is associated with WM integrity, rather than volume. 95,96 In ongoing work, we are actively investigating WM integrity in association with cognitive function using DTI in these aging vervets.…”

“…Previously, we reported declines in executive function with age in the 30 female vervets in the ongoing longitudinal study (Frye et al 38 ). In human studies, recent work suggests that executive function is associated with WM integrity, rather than volume 95,96 . In ongoing work, we are actively investigating WM integrity in association with cognitive function using DTI in these aging vervets.…”

White matter integrity mediates the associations between white matter hyperintensities and cognitive function in patients with silent cerebrovascular diseases

“…Its function is not clear, but it has been suggested to play an important role in executive function 37 . The findings of a recent study showed that the IFOF and the fronto‐parietal white matter of the genu of the corpus collosum mediate the association between age and executive function in healthy aging and that the WMH burden within these white matter tracts influences this association 38 . This implies that the related fibers may play an important role as carriers underlying brain‐behavior associations.…”

Multimodal MRI cerebral correlates of verbal fluency switching and its impairment in women with depression

“…Among the MDD participants, we expect switching performances to be associated with thinner cortices among cortical regions involved in executive functions such as the frontal gyri ( Yuan and Raz, 2014 ) and semantic VF (such as the temporal cortices) ( Vonk et al, 2019 ). Similarly, we expected decreased FA among white matter tracts both involved in cognitive switching, semantic classification and verbal fluency, such as the superior longitudinal fasciculus (SLF) and the inferior fronto-occipital fasciculus (IFOF) ( Hoagey et al, 2021 , Garcin et al, 2018 , Li et al, 2017 ).…”