Lack of association between ¹¹C-PiB and longitudinal brain atrophy in non-demented older individuals☆

Abstract 

Amyloid-β plaques (Aβ) are a hallmark of Alzheimer's disease (AD), begin deposition decades before the incipient disease, and are thought to be associated with neuronal loss, brain atrophy and cognitive impairment. We examine associations between ¹¹C-PiB-PET measurement of Aβ burden and brain volume changes in the preceding years in 57 non-demented individuals (age 64–86; M=78.7). Participants were prospectively followed through the Baltimore Longitudinal Study of Aging, with up to 10 consecutive MRI scans (M=8.1) and an ¹¹C-PiB scan approximately 10 years after the initial MRI. Linear mixed effects models were used to determine whether mean cortical ¹¹C-PiB distribution volume ratios, estimated by fitting a reference tissue model to the measured time activity curves, were associated with longitudinal regional brain volume changes of the whole brain, ventricular CSF, frontal, temporal, parietal, and occipital white and gray matter, the hippocampus, orbito-frontal cortex, and the precuneus. Despite significant longitudinal declines in the volumes of all investigated regions (p<0.05), no associations were detected between current Aβ burden and regional brain volume decline trajectories in the preceding years, nor did the regional volume trajectories differ between those with highest and lowest Aβ burden. Consistent with a threshold model of disease, our findings suggest that Aβ load does not seem to affect brain volume changes in individuals without dementia.

Keywords: Alzheimer's disease, BLSA, Volumetric MRI, Normal aging: PET, ¹¹C-PiB