Basal Cerebral Metabolism May Modulate the Cognitive Effects of Aβ in Mild Cognitive Impairment: An Example of Brain Reserve

• Published in: The Journal of neuroscience Vol. 29; no. 47; pp. 14770 - 14778
• Main Authors: Cohen, Ann D., Price, Julie C., Weissfeld, Lisa A., James, Jeffrey, Rosario, Bedda L., Bi, Wenzhu, Nebes, Robert D., Saxton, Judith A., Snitz, Beth E., Aizenstein, Howard A., Wolk, David A., DeKosky, Steven T., Mathis, Chester A., Klunk, William E.
• Format: Journal Article
• Language: English
• Published: Society for Neuroscience 25.11.2009
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3669-09.2009

Inverse correlations between amyloid-β (Aβ) 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 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.