Cerebrovascular reactivity is related to peripheral endothelial function among healthy postmenopausal women but not midlife and older men

Abstract

Background Age is the primary risk factor for cardiovascular diseases (CVD), cognitive decline, Alzheimer's disease and related dementias. Young women are at a lower risk for the above-mentioned diseases compared to age-matched men; however, their risk becomes greater than men after menopause. Age-related declines in peripheral and cerebral vascular function are thought to play a role in the increased risk for CVD and related chronic conditions. It is often assumed that changes in peripheral vascular function are directly indicative of changes in cerebrovascular function. However, in young, healthy adults, there does not appear to be an association between peripheral and cerebral vascular function. There is still limited evidence for whether peripheral vascular function is indicative of cerebrovascular function in postmenopausal (PM) women and midlife and older (ML/O) men. Purpose To determine the relation between cerebrovascular reactivity (CVR; an index of cerebrovascular function) and vascular endothelial function (brachial artery flow-mediated dilation [FMDBA]) in PM women and ML/O men and to determine if cerebrovascular function is associated with cognitive function in these groups. Methods CVR, FMDBA, and cognitive function were assessed in 17 PM women (67±6 years) and 26 men (66±7 years). Middle cerebral artery velocity (MCAv; cm/s) using a 2-MHz transcranial Doppler probe and end-tidal CO2 (etCO2; mmHg) were measured during 5 minutes of normocapnia and 5 minutes of hypercapnia (5% CO2). CVR was calculated as ΔMCAv/ΔetCO2. FMDBA was determined with the forearm cuff method and data expressed as Δ% from baseline diameter. The NIH Toolbox Cognition Battery of tests was used to assess global cognitive function, as well as specific cognitive domains. Results CVR was correlated with FMDBA (r=0.33, p=0.02) in PM women but was not correlated with FMDBA in ML/O men (r<0.01, p=0.85). There was a significant difference in this relation between sexes (p=0.04). Stepwise linear regression identified CVR and body mass index (BMI), but not age, blood pressures, LDL and HDL cholesterol, triglycerides or glucose, as significantly related to FMD­BA in PM women; correcting for BMI strengthened the relation between CVR and FMDBA in PM women (r=0.62, p<0.01). In contrast, only plasma LDL cholesterol and triglycerides were significantly related to FMD­BA in ML/O men. There were no relations between CVR and cognitive function in PM women (all p>0.05). In men there was a significant positive relation between CVR and the picture vocabulary test measure of language (r=0.56, p<0.01), but no other measures of cognitive function (all p>0.05). Conclusions These findings suggest cerebrovascular function is associated with peripheral vascular endothelial function in PM women, but not ML/O men, while cerebrovascular function has no to minimal relation to cognitive function in these groups. Controlling for BMI increased the strength of the relation between CVR and FMD­BA in PM women, indicating that body composition may be an important factor influencing cerebrovascular function in these women.