Interactive effects of vascular risk burden and advanced age on cerebral blood flow

Katherine J Bangen, Daniel A Nation, Lindsay R Clark, Alexandrea L Harmell, Christina E Wierenga, Sheena I Dev, Lisa Delano-Wood, Zvinka Z Zlatar, David P Salmon, Thomas T Liu, Mark W Bondi, Katherine J Bangen, Daniel A Nation, Lindsay R Clark, Alexandrea L Harmell, Christina E Wierenga, Sheena I Dev, Lisa Delano-Wood, Zvinka Z Zlatar, David P Salmon, Thomas T Liu, Mark W Bondi

Abstract

Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines.

Keywords: aging; arterial spin labeling; cognition; vascular risk factors.

Figures

Figure 1
Figure 1
Interaction of age and vascular risk burden on cerebral blood flow (CBF) for four a priori cortical regions of interest. Interactions were statistically significant for the medial temporal, inferior parietal, and frontal regions of interest (p-values < 0.05) and there was a trend toward an interaction for posteromedial CBF (p = 0.12). High vascular risk indicates the presence of two or more vascular risk factors whereas low vascular risk indicates the presence of no or one vascular risk factor.
Figure 2
Figure 2
Scatterplots of correlations between cerebral blood flow and cognitive performance for older adults with elevated vascular risk burden. (A) Correlation between memory performance and medial temporal lobe cerebral blood flow (p = 0.13), (B) Correlation between executive function performance and frontal cerebral blood flow (p = 0.001), and (C) Correlation between executive function performance and inferior parietal cerebral blood flow (p < 0.001). Higher scores on Trails B represent poorer (slower) performance.

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