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

Abstract

Cerebral white matter damage is not only 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.

Figure 1

Association Between Cognition and DTI Measures. Associations between performance on the three different tasks, TMT A, TMT B, and SCWT and fractional anisotropy (FA) (left) and the same associations for radial diffusivity (right). Blue indicates a negative association, red indicates a positive association as indicated on the colorbar. TMT A, Trail Making Test part A; TMT B, Trail Making Test part B; SCWT, Stroop Color Word Task; FA, Fractional Anisotropy, P < 0.05. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Influence of MABP or WMSA on the association between FA and cognition. The influence of MABP (middle) or WMSA (right) on the association between FA and the three cognitive tasks (left) TMT A, TMT B, and SCWT. TMT A, trail making Test part A; TMT B, Trail Making Test part B; SCWT, Stroop Color Word Task; MABP, mean arterial blood pressure, WMSA, white matter signal abnormalities. P < 0.05. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

The full model for structural equation modeling analyses. The full model used for the SEM analyses for each diffusivity metric separately. E represents the error term for each included variable. MABP, mean arterial blood pressure; WMSA, white matter signal abnormalities; DTI, diffusion tensor imaging.

Figure 4

Final reduced models for the associations between DTI and cognition. The reduced models that explains best the relationship between the different diffusivity metric and cognition: A, FA; B, ADC, C, Axial diffusivity, D, Radial diffusivity. E represents the error term for each included variable. FA, fractional anisotropy; ADC, apparent diffusion coefficient; WMSA, white matter signal abnormalities.

Figure 5

Spatial distribution of WMSA relative to the DTI clusters associated with cognition. The number of participants with WMSA (green, five participants—maximum participants) relative to the significant FA clusters associated with TMT A, TMT B or SCWT performance. TMT A, Trail Making Test part A; TMT B, Trail Making Test part B; SCWT, stroop color word task. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]