Brain β-Amyloid and Atrophy in Individuals at Increased Risk of Cognitive Decline.

Abstract

The relationship between brain β-amyloid and regional atrophy is still incompletely understood in elderly individuals at risk of dementia. Here, we studied the associations between brain β-amyloid load and regional GM and WM volumes in older adults who were clinically evaluated as being at increased risk of cognitive decline based on cardiovascular risk factors. Forty subjects (63-81 years of age) were recruited as part of a larger study, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. Neuroimaging consisted of PET using 11C Pittsburgh compound-B and T1-weighted 3D MR imaging for the measurement of brain β-amyloid and GM and WM volumes, respectively. All subjects underwent clinical, genetic, and neuropsychological evaluations for the assessment of cognitive function and the identification of cardiovascular risk factors. Sixteen subjects were visually evaluated as showing cortical β-amyloid (positive for β-amyloid). In the voxel-by-voxel analyses, no significant differences were found in GM and WM volumes between the samples positive and negative for β-amyloid. However, in the sample positive for β-amyloid, increases in 11C Pittsburgh compound-B uptake were associated with reductions in GM volume in the left prefrontal (P = .02) and right temporal lobes (P = .04). Our results show a significant association between increases in brain β-amyloid and reductions in regional GM volume in individuals at increased risk of cognitive decline. This evidence is consistent with a model in which increases in β-amyloid incite neurodegeneration in memory systems before cognitive impairment manifests.