β‐amyloid burden is not associated with rates of brain atrophy

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Abstract
Objective To test the hypothesis that β‐amyloid (Aβ) burden is associated with rates of brain atrophy. Methods Forty‐five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease who had two volumetric head magnetic resonance imaging scans were identified. Compact and total (compact + diffuse) Aβ burden was measured using a computerized image analyzer with software program to detect the proportion of gray matter occupied by Aβ. Visual ratings of Aβ burden were also performed. The boundary shift integral was used to calculate change over time in whole‐brain and ventricular volume. All boundary shift integral results were annualized by adjusting for scan interval. Demographics, cognitive measures, clinical diagnoses, apolipoprotein E genotype, neurofibrillary tangle (NFT) pathology, and vascular lesion burden were determined. Results There was no correlation between compact or total Aβ burden, or visual Aβ ratings, and rates of brain loss or ventricular expansion in all subjects. However, significant correlations were observed between rates of brain loss and age, Braak NFT stage, and change over time in cognitive measures. These features also correlated with rates of ventricular expansion. The rates of brain loss and ventricular expansion were greater in demented compared with nondemented subjects. Interpretation These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Aβ in the gray matter. Ann Neurol 2007