DIFFERENTIAL EFFECT OF GLUCOSE METABOLISM AND INTRINSIC FUNCTIONAL CONNECTIVITY ON MEMORY PERFORMANCE OVER THE SPECTRUM OF ALZHEIMER'S DISEASE

Abstract

While alterations in glucose metabolism are a well-established feature of Alzheimer's disease and linked to cognitive decline, aberrant patterns of spontaneous neural activity at rest are increasingly recognized as a characteristic of the disorder and are also evident in preclinical stages. The regional interrelationship of glucose consumption and resting-state activity and the differential contributions of these measures to memory function are still not well understood. The aim of the present study was to characterize this relationship and to assess the individual effects of the two modalities on memory function. Patients with subjective memory complaints (n=11), mild cognitive impairment (MCI) due to Alzheimer's disease (n=9), and early stage Alzheimer's dementia (n=10) were included in the analysis. We simultaneously acquired resting-state functional MRI (rs-fMRI) and [18F]fluorodeoxyglucose (FDG) PET data using a hybrid PET-MRI scanner. Independent component analysis was used to decompose rs-fMRI data into 75 spatially independent components of temporally synchronized neural activity. Using a combination of automated methods, we selected two default mode network components for the subsequent analysis. We performed voxel-wise regression analysis of intrinsic network connectivity and [18F]FDG uptake in the selected networks, correcting for voxelwise effects of gray matter volume. Mean values for both modalities were extracted from brain regions showing a significant effect of glucose consumption on intrinsic functional connectivity (p < 0.05 FWE-corrected) and entered into multiple regression models to estimate their effect on verbal memory performance (delayed recall of Logical Memory). Within the whole group, glucose uptake was significantly positively correlated with intrinsic connectivity in the ventral default mode network. Crucially, intrinsic connectivity but not glucose uptake predicted memory performance in patients with Alzheimer's disease (in the combined group of MCI and early stage dementia patients, as well in the early stage dementia group only). While glucose metabolism and intrinsic functional connectivity of resting state networks are closely interrelated, the disruption of functional connectivity in the default mode network better predicts memory performance. These results contribute to the development of rs-fMRI changes as a diagnostic marker and potential therapeutic target for Alzheimer's disease.