CDI Test Shows Early Detection Potential in Alzheimer’s

Breakthrough Study Highlights Brain Blood Flow Dynamics in Alzheimer’s Disease

New research from USC Viterbi School of Engineering has uncovered a critical role of cerebral blood flow regulation in Alzheimer’s disease (AD), offering a potential non-invasive diagnostic approach. Led by Vasilis Marmarelis, the team demonstrated that measuring how the brain’s vessels respond to carbon dioxide and pressure fluctuations may outperform traditional diagnostic tools like amyloid PET scans and cognitive tests. This finding could provide clinicians with a more accessible method to detect mild cognitive impairment (MCI) and early-stage Alzheimer’s.

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Autoregulatory Dysfunction as a Marker for Cognitive Decline in Alzheimer’s

While Alzheimer’s diagnosis has historically centered on detecting amyloid beta plaques and tau tangles, these approaches have limitations, ranging from invasiveness to cost and accessibility. Marmarelis and his team shifted focus to cerebral autoregulation, the brain’s ability to maintain stable blood flow despite changes in blood pressure and CO₂ levels. Impairment in this autoregulatory function, known as vasomotor dysfunction, means that neurons may not receive sufficient oxygen and nutrients during cognitive activity, accelerating cognitive decline.

“Physicians take the emissions from that PET radioactive tracer as an approximate measure of how much amyloid or tau the person has in their brain. Speaking from experience, after having seen data in my own study, I tell you that it’s very inadequate. But it’s the gold standard, although most physicians don’t do it because it’s very expensive.”

Vasilis Marmarelis, Biomedical Engineering Department, University of Southern California

The study introduces the Cerebrovascular Dynamics Index (CDI), which quantifies how effectively the brain’s vessels respond to physiological changes. Using Doppler ultrasound to measure arterial blood flow and near-infrared spectroscopy to monitor cortical oxygenation, CDI captures the dynamic interplay of vascular response in real time. Remarkably, the CDI achieved an AUC of 0.96, outperforming traditional PET imaging and cognitive tests like MMSE and MoCA. For clinicians, this signals a non-invasive, reliable marker for identifying mild cognitive impairment (MCI) and early Alzheimer’s, paving the way for interventions before significant neuronal damage occurs.

Clinical Implications and Potential Therapies 

The findings have wide-reaching implications for neurologists, geriatricians, and other HCPs. Early detection using CDI could allow for timely interventions focused on restoring healthy cerebral perfusion. Potential therapeutic strategies include regular aerobic exercise, adherence to brain-healthy diets such as the MIND diet, intermittent hypoxia-hypercapnia protocols, and non-invasive transcutaneous auricular vagal neurostimulation (taVNS). These interventions aim to optimize cerebral blood flow regulation, potentially slowing cognitive decline and improving quality of life. The study, funded by NIH grants and published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, involved multidisciplinary collaboration across USC, Kansas University Medical Center, and the University of Texas Southwestern Medical Center.

Key Takeaway: This research highlights that cerebral blood flow dysregulation may be a fundamental factor in Alzheimer’s pathogenesis, offering clinicians a practical, non-invasive tool to detect and monitor disease progression while informing targeted therapeutic strategies.

For More Information:

Marmarelis, V., et al. (2025). Dysregulation of cerebral perfusion dynamics is associated with Alzheimer’s disease. Alzheimer S & Dementia Diagnosis Assessment & Disease Monitoring. University of Southern California