Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve.
Inverse correlations between amyloid-beta (Abeta) load measured by Pittsburgh Compound-B (PiB) positron emission tomography (PET) and cerebral metabolism using [(18)F]fluoro-2-deoxy-d-glucose (FDG) in Alzheimer's disease (AD) patients, suggest local Abeta-induced metabolic insults. However, this relationship has not been well studied in mild cognitive impairment (MCI) or amyloid-positive controls. Here, we explored associations of Abeta deposition with metabolism via both region-of-interest-based and voxel-based analyses in amyloid-positive control subjects and patients with MCI or AD. Metabolism in parietal and precuneus cortices of AD patients was negatively correlated with PiB retention locally, and more distantly with PiB retention in frontal cortex. In amyloid-positive controls, no clear patterns in correlations were observed. In MCI patients, there were essentially no significant, negative correlations, but there were frequent significant positive correlations between metabolism and PiB retention. Metabolism in anterior cingulate showed positive correlations with PiB in most brain areas in MCI, and metabolism and PiB retention were positively correlated locally in precuneus/parietal cortex. However, there was no significant increase in metabolism in MCI compared to age-matched controls, negating the possibility that Abeta deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating Abeta deposition or increasing the level of Abeta necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive Abeta deposition has been present for longer periods of time does Abeta become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.
Cohen
Ann D
AD
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Price
Julie C
JC
Weissfeld
Lisa A
LA
James
Jeffrey
J
Rosario
Bedda L
BL
Bi
Wenzhu
W
Nebes
Robert D
RD
Saxton
Judith A
JA
Snitz
Beth E
BE
Aizenstein
Howard A
HA
Wolk
David A
DA
Dekosky
Steven T
ST
Mathis
Chester A
CA
Klunk
William E
WE
D000222:Adaptation, Physiological / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001481:Basal Metabolism / Q000502:physiology*; D001931:Brain Mapping; D054022:Cerebrum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000378:metabolism; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides