Changes in premorbid brain volume predict Alzheimer's disease pathology.
OBJECTIVE
To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology.


METHODS
Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI.


RESULTS
Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results.


CONCLUSIONS
MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.
Silbert
L C
LC
Aging and Alzheimer's Disease Center, Department of Neurology, Oregon Health and Science University, Portland 97201, USA. silbertl@ohsu.edu
Quinn
J F
JF
Moore
M M
MM
Corbridge
E
E
Ball
M J
MJ
Murdoch
G
G
Sexton
G
G
Kaye
J A
JA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D003072:Cognition Disorders / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles; D009922:Oregon; D058225:Plaque, Amyloid; D011237:Predictive Value of Tests; D011379:Prognosis