Dysregulation of cerebral perfusion dynamics is associated with Alzheimer's disease

• Published in: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
• Main Authors: Vasilis Marmarelis, Sandy Billinger, Elizabeth Joe, Dae Shin, Suhaib Hashem, Jasmin Rizko, Emily Hazen, Danilo Cardim, Jeff Burns, Rong Zhang, Helena C. Chui
• Format: Article
• Language: English
• Published: Wiley 2025-07-01
• Subjects: amyloid PET‐SUVR biomarker; diagnostic biomarkers for Alzheimer's disease (AD); diagnostic biomarkers for mild cognitive impairment (MCI); MMSE; MoCA; regulation of cerebral perfusion
• Online Access: https://doi.org/10.1002/dad2.70134

Abstract INTRODUCTION A novel physio‐marker, termed “cerebrovascular dynamics index” (CDI), was developed and evaluated in a multi‐center National Institutes of Health (NIH)–funded study for improved diagnosis of mild cognitive impairment (MCI) and its transition to Alzheimer's disease (AD). METHODS The CDI quantifies the regulation dynamics of cerebral perfusion and oxygenation (which adjust autonomously blood flow and oxygen delivery over time) through predictive dynamic modeling using relevant time‐series data. RESULTS Cross‐sectional results demonstrated excellent diagnostic performance of CDI in differentiating 90 MCI/AD patients from 77 controls (area under the curve (AUC) =  0.96), which surpassed the commonly used biomarker of amyloid positron emission tomography–standardized uptake value ratio (PET‐SUVR) (AUC = 0.78) or cognitive screening tests of Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) (AUC = 0.91 and 0.92, respectively). The CDI can also be used for disease staging because it differentiated 56 MCI from 34 mild AD participants (AUC = 0.98). CONCLUSION These findings offer the promise of a high‐performance diagnostic physio‐marker for MCI and AD, which can be obtained in a comfortable, rapid, and automated manner in clinical settings. Highlights Novel physio‐marker (cerebrovascular dynamics index [CDI]) quantifies the regulation dynamics of cerebral perfusion. The CDI was shown to improve mild cognitive impairment/Alzheimer's disease (MCI/AD) diagnosis (area under the curve [AUC] >0.95) relative to existing markers. The CDI is obtained non‐invasively, objectively, rapidly, and inexpensively. The CDI performance supports the key role of cerebrovascular dysfunction in AD. The CDI is obtained via dynamic modeling of hemodynamic/oxygenation time‐series data