Introduction: While cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used 4D-Flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the Circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile.
Methods: 312 patients along the AD continuum (172 middle-aged, 60 cognitively-healthy older, 44 mild cognitive impairment (MCI), and 36 AD) underwent MRI, CSF, and medical examinations. Regression was used to predict CSF biomarkers and atrophy from 4D-Flow, and ANCOVA to compare vascular health between groups.
Results: Decreased mean flow in the middle cerebral (MCA) and superior portion of the internal carotid arteries (sICA) and increased pulsatility in the MCA were associated with greater brain atrophy. Decreased mean flow in the sICA was associated with lower Aβ-42 in the CSF, a pathological biomarker profile associated with AD. Interestingly, although metrics of flow and pulsatility differed markedly across the AD spectrum, there were no significant differences in cardiovascular risk score, mean arterial pressure and pulse pressure across the three age-matched older cohorts.
Discussion: By measuring intracranial arterial health directly with 4D-Flow MRI, these data suggest that intracranial arterial health is compromised in symptomatic AD. Even after accounting for disease stage, cerebral artery health is associated with atrophy and an AD Aβ-42 profile, suggesting neurovascular health may contribute to the etiopathogenesis of AD.
Keywords: Alzheimer’s disease; Circle of Willis; cardiovascular risk; mean blood flow; pulsatility index.