Functional connectivity of the anterior and posterior hippocampus: differential effects of glucose in younger and older adults

The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory.Here we probe age, glucose and human cognition with a special emphasis on resting state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design thirty-two healthy adults (16 young and 16 older) ingested a drink containing 25g glucose or placebo across two counterbalanced sessions. They then underwent resting state functional magnetic resonance imaging and cognitive testing. There was a clear dissociation in the effects of glucose by age. In older participants rsFC between posterior hippocampus (pHPC) and medial prefrontal cortex (mPFC) increased after glucose ingestion, whereas in younger participants connectivity decreased. Magnitude change in rsFC from pHPC to mPFC was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants. This study is the first to demonstrate the selective modulation of pHPC connectivity in the acute setting.