Metabolic brain networks in aging and preclinical Alzheimer's disease

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N=64, ages 69–89) compared to young adults (N=17, ages 20–30) and patients with Alzheimer's disease (N=22, ages 69–89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease. •Healthy aging and Alzheimer's disease had opposite effects on metabolic brain networks.•Healthy aging led to widespread elevation of metabolic brain network correlations.•Alzheimer's disease led to reduced metabolic brain network correlations.•Independent metabolic function was lost in normal aging due to desegregation of ICNs.•Together Aβ and ApoE ε4 altered the metabolic brain networks in old age.