New indicators of Alzheimer’s disease risk may lie in how the brain regulates blood flow and oxygen delivery, according to a study of noninvasive cerebrovascular measurements.
Combining ultrasound and optical measurements with mathematical modeling, researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC identified cerebrovascular indicators that align with established neuroimaging markers of Alzheimer’s pathology.
“Amyloid and tau are often considered the primary players in Alzheimer’s disease, but blood flow and oxygen delivery are also critical,” said Amaryllis Tsiknia, lead author of the study and a PhD candidate at USC, in a recent press release.
To investigate these relationships, the researchers monitored cerebrovascular signals in older adults while participants rested quietly. Transcranial Doppler ultrasound was used to measure blood velocity in major brain arteries, while near-infrared spectroscopy measured oxygenation levels in cortical tissue. These signals were then analyzed using dynamic mathematical models that characterize how cerebral blood flow and oxygenation respond to natural fluctuations in blood pressure and carbon dioxide.
From these measurements, the team derived several indices describing different aspects of cerebrovascular regulation, including vascular responsiveness to carbon dioxide and the ability of blood vessels to maintain stable brain perfusion during changes in blood pressure.
Across the study cohort, higher values for these indicators – reflecting vascular behavior more similar to that of cognitively healthy adults – were associated with lower amyloid burden measured by PET imaging and with larger hippocampal volume, a brain region critical for memory. Both features are typically linked to a lower risk of Alzheimer’s disease.
“These vascular measures are capturing something meaningful about brain health,” said senior author Meredith Braskie. “They appear to align with what we see on MRI and PET scans that are commonly used to study Alzheimer’s disease.”
Participants with mild cognitive impairment or dementia also showed poorer cerebrovascular indicators compared with cognitively normal adults, supporting the idea that declining vascular regulation may be part of the Alzheimer’s disease continuum.
Because the measurements rely on relatively inexpensive and noninvasive techniques, the researchers suggest they could eventually complement existing imaging approaches. However, the study provides only a cross-sectional snapshot, and further work will be needed to determine whether these vascular signals can predict future cognitive decline.
“If we can track these signals over time, we may be able to identify people at higher risk earlier and test whether improving vascular health can slow or reduce Alzheimer’s-related brain changes,” said Tsiknia.
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