Sex differences in the rates and association of cerebral blood flow and glucose metabolism in normative ageing.

It is well established that there is a local increase in cerebral blood flow and glucose metabolism in response to neuronal events. However, there is a paucity of sex disaggregated studies measuring the relationship between cerebral blood flow and glucose metabolism, despite metabolic and vascular factors being considered primary drivers of age-related cognitive decline and dementias like Alzheimers, which disproportionally affect women. Here we address this gap by assessing the association of cerebral blood flow and glucose metabolism in the functional networks of 79 younger and older females and males, who completed a simultaneous MR/PET scan and cognitive battery. Our results extend previously reported age-related declines in CBF and CMRglc by demonstrating that their interrelationship changes with age and sex. Older age was associated with a reduction in the correlation strength between network CBF and CMRglc. CBF-CMRglc associations across people were moderated by sex, with significant negative associations in older females, a pattern not seen in older males nor younger adults. People with higher CBF-CMRglc correlations had better cognitive performance. We conclude that older adults lose synchronised vascular and metabolic dynamics in large-scale functional network, which are necessary for cognitive processes. Older females show strong, negative network CBF-CMRglc correlations, possibly reflecting a compensatory response in the face or attenuated rates of blood flow and glucose metabolism. The associations of CBF and CMRglc may serve as a biomarker for brain heath and neurological conditions.