Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden.

OBJECTIVE: To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. METHODS: Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET ß-amyloid (Aß) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aß burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aß+ vs Aß-), and the interaction between SMCs and Aß status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates. RESULTS: Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aß+ individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aß status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aß, even after adjustment for age, hippocampal volume, or depressive symptoms. CONCLUSIONS: These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline.