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

Abstract

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 b-amyloid (Ab) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Ab burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Ab 1 vs Ab 2 ), and the interaction between SMCs and Ab 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 Ab 1 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 Ab status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Ab, 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. Neurology ® 2017;88:1759-1767 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; CN 5 cognitively normal; FDG 5 fluorodeoxyglucose; FDR 5 false discovery rate; GDS 5 Geriatric Depression Scale; MFG 5 middle frontal gyrus; MGH 5 Massachusetts General Hospital; MTL 5 medial temporal lobe; PiB 5 Pittsburg compound B; ROI 5 region of interest; SMC 5 subjective memory complaint.Subjective memory complaint (SMC) is defined by self-reports of memory worsening and objective memory performance in the normal adjusted range. SMCs are common in the elderly population without dementia, with an estimated prevalence range between 22% and 56%, 1 and have been associated with increased risk of incident Alzheimer disease (AD). 2 Despite the high prevalence of self-perceived changes in memory among older adults, relatively little is known about its functional and pathologic correlates, especially in the preclinical stages of AD. This information is crucial because SMCs alone may have insufficient sensitivity and specificity to predict the development of dementia.With regard to SMCs and b-amyloid (Ab; one hallmark of AD pathology most commonly used to define the preclinical stage), previous studies have found conflicting results. Whereas most studies have reported an a...

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