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

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.

The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease

“…Taken together, these limitations may explain some of the seemingly contradictory findings in AD risk and AD-related ASL studies, including inconsistencies regarding hyperperfusion and hypoperfusion and regional differences in CBF alteration between studies. Other possible explanation for disparate findings in AD-related CBF research include patient demographics (i.e., age and vascular risk burden (Bangen et al 2014)), disease severity, and diagnostic criteria.…”

“…Elevated vascular risk burden, or the presence of vascular risk factors (e.g., diabetes, hypertension, heart disease, current smoking), is associated with an increased risk of cognitive decline and AD (Luchsinger et al 2005; Austin et al 2011; Gorelick et al 2011; Bangen et al 2014). Moreover, AD risk increases with the number of coexisting vascular risk factors present (Luchsinger et al 2005).…”

“…Recent evidence also suggests that vascular risk burden might moderate the relationship between increasing age and reduced CBF, with a relationship between advancing age and reduced CBF only observed among those possessing multiple vascular risk factors. Moreover, only those with elevated vascular risk showed an association between reduced CBF and poorer cognitive performance (Bangen et al 2014). Taken together, these studies demonstrate that CBF may be the mechanism by which elevated vascular risk burden impacts brain health and cognition, suggesting its utility in identifying those at risk for AD.…”

Cerebral Blood Flow Measured by Arterial Spin Labeling MRI as a Preclinical Marker of Alzheimer's Disease

“…The studies reviewed above tend to suggest hyperperfusion precedes hypoperfusion in earlier phases of disease development and progression (Figure 1) [23,36,37,40]. Some differences across studies may be attributable to methodological differences, such as CBF collection methods, patient demographics such as age and vascular risk burden [54], diagnostic criteria for MCI, disease severity, or misclassifying preclinical AD as normal controls. It is also possible that differences in the way CBF is coupled with local metabolic needs during different phases of disease development and progression may explain this paradoxical, biphasic early hyperperfusion followed by later hypoperfusion CBF response.…”

The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease

“…Numerous investigations have shown that LOAD risk is increased in the presence of antecedent cardiovascular (CV) risk factors, such as history of type 2 diabetes (T2D), 2,3 hypertension, smoking, 4 lipid disorders, 5 and cerebrovascular factors, alone or in aggregate. 6 Some studies suggest that CV disease (CVD) may affect dementia through multiple mechanisms, including reduction in cerebral blood flow 7 and breakdown of the blood-brain barrier. 8 …”