Macrovascular and microvascular cerebral blood flow in adults at risk for Alzheimer's disease

Abstract

Introduction: Capillary hypoperfusion is reported in asymptomatic adults at-risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown.

Methods: One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years) completed arterial spin labeling (pcASL) and 4D-flow MRI sequences. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and capillary perfusion, and tested potential moderators of this relationship.

Results: Mean arterial blood flow through middle cerebral arteries (MCAs) and internal carotid arteries was positively associated with perfusion in large cortical clusters (P < .05, false discovery rate corrected). Trends were observed for the interactions MCA flow × age and MCA flow × cardiovascular risk on cerebral perfusion (P < .001, uncorrected).

Discussion: These findings provide evidence that capillary perfusion measured via pseudocontinuous arterial spin labeling is strongly dependent on inflow from larger cerebral arteries. Further studies are warranted to investigate possible alterations between macrovascular and microvascular flow in advanced age and elevated cardiovascular risk in asymptomatic adults at risk for AD.

Keywords: Alzheimer's disease; Arterial spin labeling; Cerebral blood flow; Cerebrovascular disease; Phase-contrast MRI; Vascular imaging.

Fig. 1

Significant positive relationship between mean perfusion and mean flow in MCAs (left) and sICAs (right), adjusted for age and sex in cognitively healthy middle-aged and older adults enriched for Alzheimer's disease risk (n = 155).

Fig. 2

Results of voxel-wise analyses (t statistic map) demonstrating a positive relationship between mean flow in MCAs (top) and sICAs (bottom) and regional perfusion in cognitively healthy middle-aged and older adults (n = 155; P < .05 FDR corrected; cluster extent = 100).

Fig. 3

Results of voxel-wise analyses (t statistic map) displaying clusters in which perfusion was positively associated with the age × MCA mean flow interaction term (top panel; n = 155; P < .001 uncorrected; cluster extent = 100) or the atherosclerotic cardiovascular disease (ASCVD) risk score × MCA mean flow interaction term (bottom panel; n = 154; P < .001 uncorrected; cluster extent = 100).