Biology subjects

Di Paolo, R.

Publications and source records attributed to Di Paolo, R..

3 recordsLinked to original sources

bioRxiv2024

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.

neuroscience↗

bioRxiv2024

Insulin resistance alters the coupling between cerebral blood flow and glucose metabolism in younger and older adults: Implications for neurovascular coupling

Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of insulin resistance and age to the coupling of cerebral blood flow and glucose metabolism; a critical process in the supply of energy for the brain. Thirty-four younger (20-42 years) and 41 older (66-86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive coupling. In insulin resistant younger adults, coupling showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates and coupling of cerebral blood flow and metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

neuroscience↗

bioRxiv2022

Lower Brain Glucose Metabolism in Normal Ageing is Predominantly Frontal and Temporal: A Systematic Review and Pooled Effect Size and Activation Likelihood Estimates Meta-Analyses.

This review provides a qualitative and quantitative analysis of cerebral glucose in ageing. We undertook a systematic review of the literature followed by pooled effect size and Activation Likelihood Estimates (ALE) meta-analyses. Studies were retrieved from PubMed following the PRISMA guidelines. After reviewing 653 records, 22 studies with 24 samples (n = 993 participants) were included in the pooled effect size analyses. Eight studies with 11 samples (n = 713 participants) were included in the ALE analyses. Pooled effect sizes showed significantly lower cerebral metabolic rates of glucose for older versus younger adults for the whole brain, as well as for the frontal, temporal, parietal and occipital lobes. Among the sub-cortical structures, the caudate showed a lower metabolic rate among older adults. In sub-group analyses controlling for changes in brain volume or partial volume effects, the lower glucose metabolism among older adults in the frontal lobe remained significant, whereas confidence intervals crossed zero for the other lobes and structures. The ALE identified nine clusters of lower glucose metabolism among older adults, ranging from 200mm3 to 2,640mm3. The two largest clusters were in the left and right inferior frontal and superior temporal gyri and the insula. Clusters were also found in the inferior temporal junction, the anterior cingulate and caudate. Taken together, the results of the meta-analyses are consistent with research showing less efficient glucose metabolism in the ageing brain. The findings are discussed in the context of theories of cognitive ageing and are compared to those found in neurodegenerative disease.

neuroscience↗