Vascular Brain Injury Greater Risk Factor Than Amyloid Plaques in Cognitive Aging Processes

Vascular brain injury from disorders such as stroke and high blood pressure are greater risk factors for cognitive impairment among nondemented older individuals than is the amyloid plaques accumulation of the brain that long have been implicated in conditions such as Alzheimer’s disease (AD), new findings have revealed.

Published online February 11, 2012, in JAMA Neurology (formerly Archives of Neurology), the study found that vascular brain injury had by the greatest influence across a variety of cognitive domains, including the forgetfulness of mild cognitive decline and higher-level thinking.

The researchers in addition tried to determine whether there was a link between vascular brain injury and the deposition of beta amyloid (Αβ) plaques, thought to be an early and important marker of Alzheimer’s disease, said Bruce Reed, associate director of the University of California (UC) Davis Alzheimer’s Disease Research Center (Martinez, CA, USA). They also attempted to decode what effect each has on memory and executive functioning.

“We looked at two questions,” said Dr. Reed, professor in the department of neurology at UC Davis. “The first question was whether those two pathologies correlate to each other, and the simple answer is ‘no.’ Earlier research conducted in animals, has suggested that having a stroke causes more beta amyloid deposition in the brain. If that were the case, people who had more vascular brain injury should have higher levels of beta amyloid. We found no evidence to support that. The second was whether higher levels of cerebrovascular disease or amyloid plaques have a greater impact on cognitive function in older, nondemented adults. Half of the study participants had abnormal levels of beta amyloid and half vascular brain injury, or infarcts. It was really very clear that the amyloid had very little effect, but the vascular brain injury had distinctly negative effects. The more vascular brain injury the participants had, the worse their memory and the worse their executive function--their ability to organize and problem solve.”

The research was performed in 61 male and female study participants who ranged in age from 65 to 90 years old, with a median age of 78. Thirty of the participants were clinically “normal,” 24 were cognitively impaired, and seven were diagnosed with dementia, based on cognitive testing. The participants had been recruited from Northern California between the years 2007 to 2012.

The study participants underwent magnetic resonance imaging (MRI)—to measure vascular brain injury—and positron emission tomography (PET) scans to measure beta amyloid deposition: markers of the two most common pathologies that affect the aging brain. Vascular brain injury emerges as brain infarcts and white matter hyperintensities in MRI scans, regions of the brain that appear bright white.

The study demonstrated that both memory and executive function correlated negatively with brain infarcts, particularly infarcts in cortical and subcortical gray matter. Although infarcts were typical in this group, the infarcts varied greatly in size and location, and many had been clinically silent. The level of amyloid in the brain did not correlate with either alterations in executive function or memory, and there was no signs that amyloid interacted with infarcts to impair thinking.

According to Dr. Reed, the research is significant because there is a vast amount of interest in detecting AD at its earliest stage, before an individual shows clinical symptoms. It is possible to perform a brain scan and identify beta amyloid in the brain, and that is a very new advance, he noted.

“The use of this diagnostic tool will become reasonably widely available within the next couple of years, so doctors will be able to detect whether an older person has abnormal levels of beta amyloid in the brain. So it’s very important to understand the meaning of a finding of beta amyloid deposition,” Dr. Reed said. “What this study says is that doctors should think about this in a little more complicated way. They should not forget about cerebrovascular disease, which is also very common in this age group and could also cause cognitive problems. Even if a person has amyloid plaques, those plaques may not be the cause of their mild cognitive symptoms.”

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