A combination of high blood pressure and decreased blood flow inside the brain may spur the buildup of harmful plaque and signal the onset of dementia, USC researchers have found.

“If you have problems with the blood vessels in the brain, then you’re going to end up with difficulty with thinking skills, cognition, memory, and ultimately this can be related to other brain pathologies such as Alzheimer’s disease,” said Daniel Nation, lead author of the study and an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences.

For the study published in the journal Brain, Nation used patient data from a national medical database, the Alzheimer’s Disease Neuroimaging Initiative housed at the Keck School of Medicine at USC, to explore whether constricted blood flow contributes to the buildup of amyloid plaque and, consequently, to the onset of dementia. He also determined a new way to calculate cerebrovascular resistance — a stiffening of the vessels that results from high blood pressure and low blood flow.

The brain tightens or relaxes its vessels to maintain blood flow as it adjusts for changes in blood pressure. However, the brain vessels in Alzheimer’s patients are stiff and tight, inhibiting blood flow and enabling the sticky amyloid to accumulate, Nation found.

“The idea of cerebrovascular resistance converges on the notion that the blood vessels in Alzheimer’s brains are in this hyper–contracted state,” Nation said. “For many different reasons, the contracting blood vessels are resistant to opening up and really letting the blood in.”

Blood pressure and blood flow measures alone do not predict dementia as well as when they are examined together.

“When blood pressure goes up or down, the brain vessels accommodate so that blood flow will remain fixed,” Nation said. “So if you don’t measure blood pressure and blood flow together, then it is basically masking all of these important changes in vascular resistance, and it is very difficult to see the vessel changes that underlie this.”

To measure resistance in the brain’s vessels, Nation developed an index that represents a ratio of average blood pressure to regional cerebral blood flow. A high index ranking for resistance indicates that amyloid is building up and that the patient is progressing toward dementia, Nation said.

The Alzheimer’s Disease Neuroimaging Initiative database used for the study is an extensive repository of medical data from an estimated 1,000 volunteers age 55–90. The data include results of genetic, memory and cognitive tests, brain scans and blood biomarker information.

Nation used data on three groups of volunteers: 112 men and women who did not have any amyloid buildup in their brains, 87 who did and 33 who had Alzheimer’s.

To measure resistance in the brain’s vessels, Nation developed an index that represents a ratio of average blood pressure to regional cerebral blood flow. A high index ranking for resistance indicates that amyloid is building up and that the patient is progressing toward dementia, Nation said.

Nation found that the 33 people with Alzheimer’s had lower blood flow in their brains than the people without dementia. These blood flow changes were undetectable in the earlier stages of the disease, when amyloid was accumulating, but there were no obvious signs of memory loss.

The people with Alzheimer’s also measured much higher on the cerebrovascular resistance index.

Amyloid–positive patients’ cognition worsened over time. Nation found that just two years after their initial examination, they were more likely to experience accelerated cognitive decline and progression to clinical dementia.