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β‐amyloid burden is not associated with rates of brain atrophy
Author(s) -
Josephs Keith A.,
Whitwell Jennifer L.,
Ahmed Zeshan,
Shiung Maria M.,
Weigand Stephen D.,
Knopman David S.,
Boeve Bradley F.,
Parisi Joseph E.,
Petersen Ronald C.,
Dickson Dennis W.,
Jack Clifford R.
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21223
Subject(s) - atrophy , amyloid (mycology) , amyloid β , medicine , neuroscience , pathology , psychology , disease
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