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

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.