Metabolic connectivity in ageing.

Information transfer across the brain has a high energetic cost and requires the efficient use of glucose. Positron emission tomography (PET) studies have shown that ageing is associated with a decline in regional rates of cerebral glucose metabolism. However, until recently, it has not been possible to measure the timecourse of molecular activity within an individual using PET, preventing the study of metabolic network connectivity across the brain. Here we report the results of the first high temporal resolution functional PET study examining metabolic connectivity and cognitive function in ageing. The metabolic connectomes of 40 younger (mean age 27.9 years; range 20-42) and 46 older (mean 75.8; 60-89) adults were characterised by high connectivity strength in the frontal, temporal, motor, parietal and medial cortices. Ageing was associated with lower global integration of metabolic hub regions, indicating disrupted information transfer across the metabolic network in older adults. In younger adults, a high proportion of glucose was used to support hubs in the frontal regions. Older adults had a smaller energy budget in comparison to younger adults, and older adults used a higher proportion of energy to support mostly posterior hub regions. This difference in the metabolic network topology in older adults was associated with worse cognitive performance. We conclude that ageing is associated with reduced metabolic connectivity, an altered metabolic network topology and a high glucose cost in hub regions. Our results highlight the fundamental role that metabolism plays in supporting information transfer in the brain and the unique insights that metabolic connectivity provides into the ageing brain.