Cardiovascular disease risk is associated with middle cerebral artery blood flow velocity in older adults.

PURPOSE: The aim of this study was to evaluate the relationship of cardiovascular disease (CVD) on middle cerebral blood flow velocity (MCAv) at rest and during exercise. A secondary aim was to explore the relationship between MCAv and 1) the presence of white matter lesions and 2) cognitive function. METHODS: We recruited individuals who were cognitively normal older adults. CVD risk was assessed by the Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk score. Transcranial Doppler ultrasound measured middle cerebral artery at rest and during a bout of moderate intensity exercise. We quantified white matter lesions from MRI and cognitive function outcomes included executive function, language, processing speed, and attention. RESULTS: Seventy-two participants 70.1 ± 4.7 years of age completed the study protocol. ASCVD risk score was significantly associated with resting and exercise MCAv (p<0.01) but not associated with white matter lesions (p>0.468). We observed a significant association between resting and exercise MCAv and language processing (p=0.010) but not other cognitive domains. CONCLUSION: In cognitively normal older adults, higher ASCVD risk score was associated with blunted resting and exercise MCAv and with lower language processing performance. These results highlight the need for CVD risk management to maintain optimal brain health.

Vascular Health is Associated with Amyloid-ß in Cognitively Normal Older Adults.

BACKGROUND: Vascular health is closely related to Alzheimer's disease (AD). Vascular function measured by flow mediated dilation (FMD) or pulsatility index (PI) can be used as marker of peripheral and central vascular health but is poorly characterized in those at risk for AD. OBJECTIVE: To assess the relationship of peripheral and central vascular function with amyloid-ß (Aß) and white matter lesion burden among cognitively normal older adults. METHODS: We enrolled participants 65 years of age and older. Using Doppler ultrasound, we assessed brachial artery FMD, and middle cerebral artery (PI). Global Aß burden, quantified using [18F] Florbetapir PET imaging, and white matter lesion volume (WML) were used as measures of AD pathology and vascular brain injury. RESULTS: After adjusting for age and cardiovascular risk factors, the data (n = 83) showed a negative association between FMD and Aß burden (ß= -0.03, p < 0.001). FMD at a cut-off of 4.45% had 88% specificity and 75% sensitivity to elevated Aß (AUC = 0.86, 95% CI: 0.77-0.95). FMD was not related to WML volume (p = 0.8), and PI was unrelated to Aß burden or WML volume (0 > 0.4). CONCLUSIONS: Among cognitively normal older adults, blunted peripheral vascular function, as measured by brachial artery FMD, is associated with Aß burden. These findings provide support for further exploration into the pathophysiological relationship of vascular health and AD risk as measured by Aß.

Blunted cerebrovascular response is associated with elevated beta-amyloid.

The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR ( n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals ( n = 45, age 72.0 ± 4.9; 7.2 ± 5.0 cm/s, p < 0.001). Further, greater beta-amyloid burden was linearly associated with less CVR across all participants (b = -11.7, p < 0.001). Greater CVR and less beta-amyloid burden were associated with processing speed ( p < 0.05). This study is the first to show that CVR from rest to exercise is blunted across increased global beta-amyloid burden.