Brain imaging evidence of preclinical Alzheimer's disease in normal aging.
OBJECTIVE
This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people.


METHODS
We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini-Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores.


RESULTS
Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid-temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini-Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini-Mental State Examination decline.


CONCLUSIONS
These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology.
Jagust
William
W
School of Public Health, University of California, Berkeley, USA.
Gitcho
Amy
A
Sun
Felice
F
Kuczynski
Beth
B
Mungas
Dan
D
Haan
Mary
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006630:Hispanic or Latino; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008297:Male; D011939:Mental Recall / Q000502:physiology; D008609:Mental Status Schedule / Q000706:statistics & numerical data; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D049268:Positron-Emission Tomography
D019788:Fluorodeoxyglucose F18; D005947:Glucose