Study connects vascular health to early Alzheimer’s brain changes

Subtle changes in how blood flows through the brain and how brain tissue uses oxygen may be closely linked to Alzheimer's disease risk, according to new research from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC.

In a study published in Alzheimer's and Dementia: The Journal of the Alzheimer's Association, Stevens INI researchers found that noninvasive measures of brain blood flow and oxygenation were associated with hallmark brain changes in older adults with and without cognitive impairment, including amyloid buildup and a smaller hippocampus, a region essential for memory. The findings suggest that vascular health of the brain may play an important role early in the disease process and could help identify individuals at risk before significant symptoms appear.

Amyloid and tau are often considered the primary players in Alzheimer's disease, but blood flow and oxygen delivery are also critical. 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."

Amaryllis A. Tsiknia, lead author of the study and USC PhD candidate

The research team used two noninvasive tools that can be applied while a person rests quietly. Transcranial Doppler ultrasound measures how fast blood moves through major brain arteries, while near-infrared spectroscopy measures how well oxygen reaches brain tissue near the surface of the cortex. Advanced mathematical models were then used to summarize these signals into indicators that reflect how well the brain adjusts blood flow and oxygen delivery in response to natural changes in blood pressure and carbon dioxide levels.

Higher values on these indicators, meaning brain blood vessels behaved more like those of cognitively healthy adults, were linked to lower levels of amyloid plaques and larger hippocampal volume. Both of these brain features are associated with a lower risk of Alzheimer's disease.

"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."

The study also found that participants with mild cognitive impairment or dementia had poorer vascular indicators than cognitively normal adults, reinforcing the idea that declining cerebrovascular function is part of the Alzheimer's disease continuum.

"These findings add to growing evidence that Alzheimer's involves meaningful vascular contributions in addition to classic neurodegenerative changes," said Arthur W. Toga, PhD, director of the Stevens INI. "Understanding how blood flow and oxygen regulation interact with amyloid and brain structure opens new doors for early detection and potentially prevention."

The techniques used are less expensive to perform than MRI and PET scans, and because they do not require injections, radiation, or active participation from patients, they may be particularly useful for large-scale screening or for people who cannot tolerate more demanding imaging procedures.

The researchers emphasize that this study provides a snapshot in time and does not prove cause and effect. Longitudinal studies are already underway to determine whether changes in these vascular measures can predict future cognitive decline or response to interventions.

"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," Tsiknia said.