Association between white matter microstructure, executive functions, and processing speed in older adults: The impact of vascular health

Abstract

Cerebral white matter damage is a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear, however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43–87 years; N=128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS.

Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging

“…Also, consistent with the literature, we found evidence for modest phenotypic correlations between neurocognitive and white-matter integrity, particularly for tests of speed of processing (27,38,39), working and declarative memory (12,13), and IQ (14,25). However, our findings extend this work by Fig.…”

Hypertension-Related Alterations in White Matter Microstructure Detectable in Middle Age

“…This suggests that hypertension has widespread effects on brain white matter. Prior findings that alterations in white matter diffusion metrics are associated with decreased cognitive performance suggest that these changes are not benign 7,23,24 .…”

Superficial white matter as a novel substrate of age-related cognitive decline

“…Moreover, many studies have shown that age-related differences in behavioral and motor task performance are mediated by age-related variations in DWM DTI metrics (Bucur et al, 2008;Hedden et al, 2014;Holtrop et al, 2014;Jacobs et al, 2013;Kerchner et al, 2012;Madden et al, 2009). Nevertheless, in several recent studies, the relationships between DWM diffusion metrics and cognitive ability is attenuated or completely lost after accounting for the effects of age (Bennett et al, 2014;Borghesani et al, 2013;Koch et al, 2013;Lockhart et al, 2012;Metzler-Baddeley et al, 2011;Salami et al, 2012).…”