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 (11)C-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 (11)C-PiB scan approximately 10 years after the initial MRI. Linear mixed effects models were used to determine whether mean cortical (11)C-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.

Figure 1. Scatterplot of mean cortical PiB DVR by age in the BLSA neuroimaging sample

Participants were also divided into equal tertiles (N=19 each) for additional analyses involving high and low PiB-binding groups. Males are denoted in blue, females in red.

Figure 2. Predicted longitudinal trajectories by tertiles of mean PiB DVR for select brain volume changes (cm³)

Age-related changes (y-axis) in (A) whole brain volume, (B) total grey matter, (C) the hippocampus, and (D) the precuneus were not related to mean cortical PiB retention. Thin lines represent individual volumes over time for a random sample of participants; bold lines represent mean trajectories for each tertile.

Figure 3. Group differences in cortical PiB DVR between High- and Low-amyloid retention groups; all non-demented

The mean of spatially normalized parametric PiB images (Zhou et al., 2007) for the 19 individuals in the upper tertile and 19 individuals in the lower tertile determined using SPM5 (Wellcome Department of Cognitive Neurology, London, England) were overlaid on an MRI template using Amide software (Loening and Gambhir, 2003). Being in the high-amyloid group or having a mean cortical DVR score in the upper tertile does not imply that an individual has an AD-like PiB scan. The scans of participants in the present study are easily distinguishable from those in other studies examining AD patients, despite the qualitative differences between the High- and Low-amyloid groups in this non-demented sample.