Subtle changes in how blood flows through the brain and how brain cells utilize oxygen may be closely linked to the risk of developing Alzheimer’s disease, according to new research from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC. The findings, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, suggest that assessing brain vascular health could offer a new avenue for early detection and potentially, preventative strategies.
The study examined older adults, both those with and without cognitive impairment, and found a correlation between noninvasive measures of brain blood flow and oxygen levels and established hallmarks of Alzheimer’s disease – amyloid plaque buildup and a reduction in the size of the hippocampus, a brain region critical for memory.
“Amyloid and tau are often considered the primary players in Alzheimer’s disease, but blood flow and oxygen delivery are also critical,” explained Amaryllis A. Tsiknia, lead author of the study and a USC PhD candidate. “Our results show that when the brain’s vascular system functions more like it does in healthy aging, we also see brain features that are linked to better cognitive health.”
Noninvasive Assessment of Brain Circulation
Researchers utilized two painless, noninvasive techniques to assess brain circulation while participants rested quietly. Transcranial Doppler ultrasound was used to measure the speed of blood flow through the brain’s major arteries. Simultaneously, near-infrared spectroscopy evaluated the efficiency of oxygen delivery to brain tissue near the surface of the cortex. These readings were then combined using advanced mathematical modeling to create indicators of overall cerebrovascular function, reflecting the brain’s ability to adjust blood flow and oxygen delivery in response to natural fluctuations in blood pressure and carbon dioxide levels.
Vascular Health and Alzheimer’s Biomarkers
The study revealed that participants with vascular indicators resembling those of cognitively healthy adults tended to have lower levels of amyloid plaques and a larger hippocampal volume – both factors associated with a reduced risk of Alzheimer’s disease. This suggests a strong link between healthy blood vessels and better brain health.
“These vascular measures are capturing something meaningful about brain health,” said Meredith N. Braskie, PhD, senior author of the study and assistant professor of neurology at the Keck School of Medicine. “They appear to align with what we see on MRI and PET scans that are commonly used to study Alzheimer’s disease, providing important information about how vascular health and standard brain measures of Alzheimer’s disease risk may be related.”
individuals diagnosed with mild cognitive impairment or dementia exhibited weaker vascular function compared to those with normal cognitive function. This observation reinforces the idea that declining brain blood vessel health is an integral part of the progression of Alzheimer’s disease.
Expanding the Understanding of Alzheimer’s Disease
Arthur W. Toga, PhD, director of the Stevens INI, emphasized the growing body of evidence supporting the role of vascular contributions in Alzheimer’s disease, beyond the traditionally recognized neurodegenerative changes. “Understanding how blood flow and oxygen regulation interact with amyloid and brain structure opens new doors for early detection and potentially prevention,” he stated.
Potential for Broader Screening and Early Intervention
The techniques employed in the study offer potential advantages over current diagnostic methods like MRI and PET imaging. They are less expensive, easier to administer, and do not involve injections, radiation exposure, or demanding tasks for patients. This simplicity could facilitate large-scale screening programs or provide a viable option for individuals unable to undergo more intensive brain imaging.
However, the researchers caution that the findings represent a snapshot in time and do not definitively establish a cause-and-effect relationship. Ongoing longitudinal studies are tracking participants to determine whether changes in these vascular measures can predict future cognitive decline or response to treatment. The goal is to determine if monitoring these signals over time can identify individuals at higher risk earlier and assess whether improving vascular health can slow or mitigate Alzheimer’s-related brain changes.
“If People 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,” Tsiknia said.
This research builds upon existing evidence, as highlighted in a 2016 study published in Cell Molecular Neurobiology, which noted accumulating evidence suggesting that changes in brain perfusion can occur long before the clinical symptoms of Alzheimer’s disease manifest, potentially even preceding amyloid-β accumulation or brain atrophy.
The study was supported by the Office of The Director, National Institutes of Health, under Award Number S10OD032285, and by the National Institute on Aging [R01AG058162].
