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 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 mm 3 . 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.

Peripheral insulin resistance attenuates cerebral glucose metabolism and impairs working memory in healthy adults

“…These results are consistent with our recent meta-analyses showing that CMRGLC differences in ageing are largest in the frontal and temporal regions and the insula. 2 Cortical thickness explained more than 10% of the variance in CMRGLC in five of eight subcortical structures. Adding age explained a relatively small amount of additional variance (2% to 7%).…”

“…Among healthy adults, the cerebral metabolic rate of glucose (CMRGLC) has been reported in most regions to be in the order of 4-7 mg of glucose per 100ml per minute. 2 The rate of cerebral glucose metabolism is also considered to be a reliable measure of neuronal activity 1 and be related to cognitive performance in health 3 and disease. 4 Cerebral metabolism is most commonly measured in vivo with F-18 fluorodeoxyglucose (18F-FDG or FDG) Positron Emission Tomography (PET).…”

“…8 In a recent systematic review and meta-analyses of FDG-PET studies in ageing, we found consistently lower CMRGLC among older compared to younger adults. 2 Pooled effect size metaanalysis across 21 studies identified lowered CMRGLC among older adults ranging from 8% in the occipital lobe to 12% in the frontal lobe. The association between lower CMRGLC and older age was partially mediated by concurrent structural brain changes with ageing.…”

“…Our systematic review and meta-analyses summarised the available research and identified several limitations in the existing literature. Many of the studies of CMR GLC in ageing were conducted 20 or more years ago on scanners with relatively poor spatial resolution (see ref 2 and Table 1). Consequently, the in vivo quantification of CMR GLC has mostly been limited to the whole brain or the lobular level.…”

Multinuclear Magnetic Resonance Spectroscopy at Ultra-High-Field: Assessing Human Cerebral Metabolism in Healthy and Diseased States

“…The common metabolic substrates and their relevant characteristic features are summarized in Table 2. Glucose [16] Obligatory substrate for adult brain 1-2.5 mM [31] All brain cells Aging [32] AD, PD, MS [16] Lactate [33] Maintain neuroenergetics and neuroplasticity ~1 mM [34] All brain cells, synthesized in astrocytes and delivered to neurons Stress [35], Exercise [36],…”