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

Abstract

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.

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

“…Our results are also consistent with studies in which reductions in CBF were associated with declining processing speed in healthy older adults 27 and impaired memory and executive function in adults with type 2 diabetes 45,46 . They are also consistent with recent work in which we showed that lower rates of network glucose metabolism are associated with slower reaction time and psychomotor speed 28 .…”

“…Older insulin resistant adults showed a pattern of moderate (r > 0.2), positive correlations in 79% of regions. We www.nature.com/scientificreports/ recently reported the relationship between CMR GLC , age and insulin resistance in the same sample used in the current study 28 . Insulin resistance had a small, non-significant negative effect on CMR GLC in older adults.…”

“…The links between insulin resistance and reduced CMR GLC are also well established (see 9 , for review). In recent work, we demonstrated that older adults had lower CMR GLC than younger adults, but insulin resistance significantly reduced CMR GLC in younger but not older adults 28 .…”