TY - JOUR
T1 - Basal cerebral metabolism may modulate the cognitive effects of Aβ in mild cognitive impairment
T2 - An example of brain reserve
AU - Cohen, Ann D.
AU - Price, Julie C.
AU - Weissfeld, Lisa A.
AU - James, Jeffrey
AU - Rosario, Bedda L.
AU - Bi, Wenzhu
AU - Nebes, Robert D.
AU - Saxton, Judith A.
AU - Snitz, Beth E.
AU - Aizenstein, Howard A.
AU - Wolk, David A.
AU - DeKosky, Steven T.
AU - Mathis, Chester A.
AU - Klunk, William E.
PY - 2009/11/25
Y1 - 2009/11/25
N2 - Inverse correlations between amyloid-β (Aβ) load measured by PittsburghCompound-B(PiB) positron emission tomography (PET) and cerebral metabolism using [18F]fluoro-2-deoxy-D-glucose (FDG) in Alzheimer's disease (AD) patients, suggest local Aβ-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 Aβ 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 Aβ deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating Aβ deposition or increasing the level of Aβ necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive Aβ deposition has been present for longer periods of time does Aβ become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.
AB - Inverse correlations between amyloid-β (Aβ) load measured by PittsburghCompound-B(PiB) positron emission tomography (PET) and cerebral metabolism using [18F]fluoro-2-deoxy-D-glucose (FDG) in Alzheimer's disease (AD) patients, suggest local Aβ-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 Aβ 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 Aβ deposition directly caused reactive hypermetabolism. This suggests that, in MCI, higher basal metabolism could either be exacerbating Aβ deposition or increasing the level of Aβ necessary for cognitive impairment sufficient for the clinical diagnosis of AD. Only after extensive Aβ deposition has been present for longer periods of time does Aβ become the driving force for decreased metabolism in clinical AD and, only in more vulnerable brain regions such as parietal and precuneus cortices.
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U2 - 10.1523/JNEUROSCI.3669-09.2009
DO - 10.1523/JNEUROSCI.3669-09.2009
M3 - Article
C2 - 19940172
AN - SCOPUS:72449133293
SN - 0270-6474
VL - 29
SP - 14770
EP - 14778
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 47
ER -