Vascular brain injury had a greater influence on cognitive function than did beta-amyloid deposition, at least in the earliest phases of cognitive impairment, in a study examining the relative contributions of the two abnormalities in 61 elderly participants.
The findings indicate that brain infarctions should be considered in studies of mild cognitive impairment (MCI), and that reducing cerebrovascular disease may be important in preventing MCI, said Natalie L. Marchant, Ph.D., of the Helen Wills Neuroscience Institute at the University of California, Berkeley, and her associates. They reported their findings online Feb. 11 in JAMA Neurology.
Both areas of infarction and areas of beta-amyloid deposition are frequently found on imaging studies of the brain in elderly subjects, and oftentimes both are present in the same individual, the investigators said. MRI revealed at least one infarct in 56% of the participants. PET imaging with the beta-amyloid binding ligand Pittsburgh compound B (PiB) found early beta-amyloid deposition in 48%. Overall, 41% had both an infarct and tested positive for PiB while 56% had no infarct but tested positive for PiB.
The study subjects had a range of cognitive functioning based on assessments made with the Mini-Mental State Examination, the Geriatric Depression Scale, the Clinical Dementia Rating, and a battery of neuropsychological tests of executive function, verbal memory, and nonverbal memory. Overall, 30 subjects were clinically normal, 24 showed MCI (7 with amnestic, 13 with nonamnestic, and 4 with other MCI), and 7 had dementia. The subjects were participating in an ongoing multicenter study, the Aging Brain Project.
Comparisons of the subjects’ cognitive function based on neuropsychological testing with the imaging results showed that vascular brain injury strongly correlated with cognitive impairment for verbal memory and executive function, but not nonverbal memory, the investigators said (JAMA Neurol. 2013 Feb. 11 [doi:1001/2013.jamaneurol.405]).
In contrast, beta-amyloid deposition did not correlate with cognitive impairment. The lack of an association in this sample might be because such deposition is an initiating event, and the "downstream" consequences such as neuronal death and synaptic loss have not yet occurred in these subjects, Dr. Marchant and her associates said.
In contrast, they suggested that "vascular brain injury represents end-stage pathologic consequences of the vascular pathogenic process."
An infarct in the subcortical gray matter was the only significant predictor of verbal memory in a multivariate logistic regression equation that accounted for 17% of the patient sample’s variance in verbal memory. The equation included white matter hyperintensity volume, infarct location in the subcortical gray matter, PiB status, and age, sex, and other demographic variables.
Only age and educational level were significant predictors of nonverbal memory in a multivariate logistic regression equation that accounted for 48% of the patient sample’s variance in nonverbal memory.
In a multivariate logistic regression equation that explained 43% of the variance in executive function, an infarct location in the cortical gray matter and educational level were the only significant predictors.
Beta-amyloid deposition also did not correlate with vascular brain injury. It may be that both of these abnormalities are prevalent in the aging brain, often occur concomitantly, and affect cognitive function in different ways, but do not bear any causal relationship to each other, the investigators said.
This study was supported by grants from the National Institutes of Health. Dr. Marchant reported no financial conflicts of interest, but one of her associates reported ties to numerous industry sources.