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Updated: Mar 28, 2026
Author Spotlight: Noninvasive Cerebral Blood Flow Determination in Human Functional Brain Region for Diagnosis of Neurological Disorders
Published on: May 31, 2024
Intracranial Arterial 4D-Flow is Associated with Metrics of Brain Health and Alzheimer's Disease
Sara E Berman1, Leonardo A Rivera-Rivera2, Lindsay R Clark3
1Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 ; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53705 ; Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53705.
Insights
Intracranial arterial health, measured by 4D-Flow MRI, is compromised in Alzheimer's disease (AD). Poor cerebral artery health correlates with brain atrophy and AD biomarkers, suggesting a role in AD pathogenesis.
Area of Science:
- Neuroscience
- Radiology
- Vascular Biology
Background:
- Cerebrovascular disease frequently co-occurs with Alzheimer's disease (AD), with emerging evidence suggesting a direct etiological role in AD pathogenesis.
- Assessing intracranial arterial health is crucial for understanding neurovascular contributions to AD.
- 4D-Flow MRI offers a non-invasive method to evaluate cerebral blood flow and pulsatility.
Purpose of the Study:
- To investigate the association between intracranial arterial health metrics and markers of AD.
- To determine if decreased blood flow and increased pulsatility in the Circle of Willis correlate with cerebral atrophy and AD cerebrospinal fluid (CSF) biomarkers.
Main Methods:
- 312 patients across the AD continuum (including healthy controls, mild cognitive impairment, and AD) underwent 4D-Flow MRI and CSF analysis.
- Regression models predicted CSF biomarkers and brain atrophy from 4D-Flow MRI data.
- ANCOVA compared vascular health metrics between different patient groups.
Main Results:
- Reduced mean blood flow in the middle cerebral artery (MCA) and internal carotid arteries (sICA), along with increased MCA pulsatility, were linked to greater brain atrophy.
- Decreased sICA mean flow was associated with lower CSF Aβ-42 levels, a key AD biomarker.
- While vascular metrics varied across the AD spectrum, cardiovascular risk factors did not significantly differ between age-matched older cohorts.
Conclusions:
- 4D-Flow MRI directly demonstrates compromised intracranial arterial health in symptomatic AD patients.
- Cerebral artery health, assessed via 4D-Flow MRI, is independently associated with brain atrophy and AD CSF biomarker profiles.
- These findings support the hypothesis that neurovascular health plays a significant role in the etiopathogenesis of Alzheimer's disease.
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.
