The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance.

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 age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both 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. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. 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 correlation. In insulin resistant younger adults, the association 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 of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

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 metabolism in ageing. We undertook a systematic literature review followed by pooled effect size and activation likelihood estimates (ALE) meta-analyses. Studies were retrieved from PubMed following the PRISMA guidelines. After reviewing 635 records, 21 studies with 22 independent samples (n = 911 participants) were included in the pooled effect size analyses. Eight studies with eleven separate 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 200 to 2640 mm3 . 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 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.

The older adult brain is less modular, more integrated, and less efficient at rest: A systematic review of large-scale resting-state functional brain networks in aging.

The literature on large-scale resting-state functional brain networks across the adult lifespan was systematically reviewed. Studies published between 1986 and July 2021 were retrieved from PubMed. After reviewing 2938 records, 144 studies were included. Results on 11 network measures were summarized and assessed for certainty of the evidence using a modified GRADE method. The evidence provides high certainty that older adults display reduced within-network and increased between-network functional connectivity. Older adults also show lower segregation, modularity, efficiency and hub function, and decreased lateralization and a posterior to anterior shift at rest. Higher-order functional networks reliably showed age differences, whereas primary sensory and motor networks showed more variable results. The inflection point for network changes is often the third or fourth decade of life. Age effects were found with moderate certainty for within- and between-network altered patterns and speed of dynamic connectivity. Research on within-subject bold variability and connectivity using glucose uptake provides low certainty of age differences but warrants further study. Taken together, these age-related changes may contribute to the cognitive decline often seen in older adults.