Cerebral blood flow, white matter lesions and risk of hippocampal atrophy: The SMART-MR study

Abstract

Reduced cerebral blood perfusion and white matter lesions (WML) may increase risk for Alzheimer's disease. It has been suggested that particularly the hippocampus is vulnerable to hypoperfusion and ischemia. We investigated whether total parenchymal cerebral blood flow (pCBF) and WML increased risk for hippocampal atrophy in a population of patients with atherosclerotic disease. Within the SMART-MR (Second Manifestations of ARTerial disease-magnetic resonance) study, a cohort study among patients with a history of atherosclerotic disease, cross-sectional analyses were performed in 392 patients (mean age 62±9 years, 84% male). Automated brain segmentation was used to quantify volumes of WML and total brain on MRI. Using MR angiography, CBF was measured in the internal carotid arteries and basilar artery and was expressed per 100 ml brain volume. Manual volumetric measurements of the hippocampus were performed on a 3-dimensional T1-weighted MRI scan. Volumes of total hippocampus, WML and total brain were expressed relative to intracranial volume. Total mean hippocampal volume was 6.2±0.7 ml. Mean pCBF was 49.8±11.2 ml/min per 100 ml brain volume, and median WML volume was 1.26 ml (10-90% 0.41-7.41). Linear regression analysis showed that reduced parenchymal CBF was not associated with smaller hippocampal volume after adjustment for age and sex, nor after additional adjustment for vascular risk factors, lacunar infarcts and WML (β= 0.02 ml per SD decrease in pCBF; 95% CI -0.05 to 0.93). Higher WML volume was associated with smaller hippocampal volume after adjustment for age, sex, and attenuated but remained statistically significant after additional adjustment for smoking, alcohol use, body mass index, hyperlipidemia, blood pressure, diabetes mellitus and lacunar infarcts (β= -0.08; 95% CI -0.153 to -0.002). However, after adjustment for global brain atrophy, WML were no longer associated with hippocampal volume (β = -0.06; 95% CI -0.127 to 0.018). Reduced parenchymal blood flow was not associated with smaller hippocampal volumes in this population. WML were associated with smaller hippocampal volumes, independent of shared vascular risk factors, but there was no evidence of increased hippocampal volume loss compared to other brain tissue. These findings do not suggest that the hippocampus in particular is vulnerable to hypoperfusion and ischemia.