In the earliest phases of cognitive impairment, vascular brain injury may have a greater influence on cognitive function than does beta-amyloid deposition, according to a study published in the February 11 online JAMA Neurology. 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, PhD, of the Helen Wills Neuroscience Institute at the University of California, Berkeley.
The researchers examined 61 elderly participants in an ongoing multicenter study, the Aging Brain Project. MRI revealed at least one infarct in 56% of the patients. PET imaging with the beta-amyloid binding ligand Pittsburgh compound B (PiB) found early beta-amyloid deposition in 48% of the patients. Overall, 41% of participants had an infarct and tested positive for PiB, while 56% had no infarct but tested positive for PiB.
Cognitive functioning was assessed with the Mini-Mental State Examination, the Geriatric Depression Scale, the Clinical Dementia Rating, and a battery of neuropsychologic tests of executive function, verbal memory, and nonverbal memory. Overall, 30 subjects were clinically normal, 24 had MCI (seven amnestic, 13 nonamnestic, and four other MCI), and seven had dementia.
Comparisons of subjects’ cognitive function, based on neuropsychologic 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.
Beta-amyloid deposition did not correlate with cognitive impairment. The lack of an association might be explained by deposition’s status as an initiating event, the consequences of which, such as neuronal death and synaptic loss, had not yet occurred in these subjects, said Dr. Marchant.
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.
Marchant NL, Reed BR, Sanossian N, et al. The aging brain and cognition: contribution of vascular injury and Ab to mild cognitive dysfunction. JAMA Neurol. 2013 Apr 1:1-8 [Epub ahead of print].