PET-based measures of metabolic connectivity outperform fMRI-based measures of functional connectivity in predicting age and cognition

The brain relies on a constant supply of glucose and oxygen to fuel complex cognitive processes. However, until the recent development of high temporal resolution functional (18F)-fluorodeoxyglucose positron emission tomography (fPET), it has not been possible to measure the brain’s metabolic connectome in individuals. Although connectomes derived from the BOLD signal in fMRI undergo a reconfiguration in ageing, those BOLD signal changes may reflect age-related alterations in one or more metabolic, haemodynamic and vascular components of neuronal activity. Here we use simultaneous fPET/fMRI to compare metabolic and functional connectivity and test their predictive utility for healthy ageing and cognition. Whole-brain fPET connectomes showed moderate topological similarities to fMRI connectomes in 40 younger (mean age 27.9 years; range 20-42) and 46 older (mean 75.8; 60-89) adults. The within-network connectivity was lower and between-network connectivity less variable in the fPET than the fMRI connectomes. However, within and between-network connectivity and graph metrics showed more wide-spread age differences and were significantly associated with performance in more cognitive domains in fPET than fMRI. These results likely reflect that fPET directly measures dynamic glucose metabolism at the post-synaptic neuron, whereas the fMRI signal indirectly indexes neuronal metabolism and has multiple physiological underpinnings. We conclude that metabolic connectivity has greater predictive utility for age and cognition than functional connectivity and offers promise as a means for indexing glucodynamic changes in ageing and disease.