Intracranial Arterial 4D-Flow is Associated with Metrics of Brain Health and Alzheimer's Disease

Sara E Berman, Leonardo A Rivera-Rivera, Lindsay R Clark, Annie M Racine, Jon G Keevil, Lisa C Bratzke, Cynthia M Carlsson, Barbara B Bendlin, Howard A Rowley, Kaj Blennow, Henrik Zetterberg, Sanjay Asthana, Patrick Turski, Sterling C Johnson, Oliver Wieben, Sara E Berman, Leonardo A Rivera-Rivera, Lindsay R Clark, Annie M Racine, Jon G Keevil, Lisa C Bratzke, Cynthia M Carlsson, Barbara B Bendlin, Howard A Rowley, Kaj Blennow, Henrik Zetterberg, Sanjay Asthana, Patrick Turski, Sterling C Johnson, Oliver Wieben

Abstract

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.

Figures

Fig. 1
Fig. 1
PC VIPR angiogram. Schematic of a PC VIPR angiogram used for quantitative flow and pulsatility analysis. Green orthogonal analysis planes denote where measurements were taken for the 11 vessel segments. MCA and sICA, vessels that were the subject of the present study, are labeled. Abbreviations: PC VIPR, phase contrast vastly undersampled isotropic projection imaging; MCA, middle cerebral artery; sICA, superior portion of the internal carotid artery.
Fig. 2
Fig. 2
Between-group analyses of ASCVD risk score, MAP, and pulse pressure. Graphical results of the between-diagnostic group ANCOVA analyses examining (A) ASCVD risk score, (B) pulse pressure and (C), mean arterial pressure. There is no significant difference for any of these metrics in the three older age groups (cognitively healthy older adults, MCI, and AD) when age and gender are included as covariates. Graphical representations (means) are without adjustment for covariates to ease in readability of percentage risk and blood pressure axes. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; MAP, mean arterial pressure; MCI, mild cognitive impairment; ANCOVA, analysis of covariance; AD, Alzheimer's disease; CI, confidence interval.
Fig. 3
Fig. 3
Lower mean blood flow is associated with a greater degree of atrophy. Scatter plot of the results of the linear regression examining the relationship between mean flow and atrophy, controlling for age, gender, and diagnostic group. Atrophy is calculated as the ratio of CSF to gray matter + white matter. Mean flow, in both the (A) superior portion of the internal carotid artery (ICA) and the (B) middle cerebral artery (MCA), negatively predict atrophy, where subjects with lower mean flow had greater degrees of atrophy. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer's disease.
Fig. 4
Fig. 4
Higher pulsatility index is associated with a greater degree of atrophy. Scatter plot of the results of the linear regression examining the relationship between pulsatility and atrophy, controlling for age, gender, and diagnostic group. Atrophy is calculated as the ratio of CSF to gray matter + white matter. Pulsatility in the middle cerebral artery (MCA) positively predicted atrophy, where subjects with higher pulsatility (stiffer vessels) had greater degrees of atrophy. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer's disease.
Fig. 5
Fig. 5
Lower mean blood flow is associated with lower levels of CSF Aβ42. Scatter plot of the results of the linear regression examining the relationship between mean blood flow and CSF Aβ42, controlling for age, gender, and diagnostic group. Lower mean flow of the (A) superior portion of the internal carotid artery (ICA) is associated with lower levels of Aβ42 in the CSF, suggesting possible reduced amyloid clearance/increased deposition in the brain. (B) Flow in the middle cerebral artery (MCA) shows a trending relationship. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer's disease; CSF, cerebrospinal fluid; Aβ42, amyloid beta 1–42.

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Source: PubMed

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