Biology subjects

Deery, H.

Publications and source records attributed to Deery, H..

4 recordsLinked to original sources

bioRxiv2024

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.

neuroscience↗

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↗

bioRxiv2023

Metabolic rates of glucose in the brain networks of healthy adults vary as a function of age and levels of peripheral insulin resistance, and predict cognition

People with insulin resistance are at increased risk for cognitive decline. Insulin resistance has previously been considered primarily a condition of ageing but it is increasingly seen in younger adults. Here, we explore the question that changes in insulin function in early adulthood have both proximal effects, and moderate or even accelerate changes in cerebral metabolism in ageing. Thirty-six younger (mean 27.8 years) and 43 older (mean 75.5) participants completed a battery of tests, including blood sampling, cognitive assessment and a simultaneous PET/MR scan. Cortical thickness and cerebral metabolic rate of glucose were derived for 100 regions and 17 functional networks. Older adults had lower rates of regional cerebral glucose metabolism than younger adults across the brain even after adjusting for lower cortical thickness in older adults. In younger adults, higher insulin resistance was associated with attenuated rates of regional cerebral glucose metabolism, but this was not seen in older adults. The largest effects of insulin resistance in younger adults were in prefrontal, parietal and temporal regions; and in the control, salience ventral attention, default and somatomotor networks. Higher rates of network glucose metabolism were associated with lower reaction time and psychomotor speed. Higher levels of insulin resistance were associated with lower working memory. Our results underscore the importance of insulin sensitivity to brain health and cognitive function across the adult lifespan, even in early adulthood. Significance StatementWe show that preventing insulin resistance in early adulthood is important for ensuring efficient fuel supply for the brain and the maintenance of cognitive health across the adult lifespan. Glucose is the primary source of energy for the brain. Decreased glucose metabolism in the brain due to clinically significant levels of insulin resistance is associated with cognitive impairment. Although sub-clinical levels of insulin resistance have also been associated with brain changes, their impact on cerebral metabolism in healthy individuals is unclear. We showed for the first time that - while older adults have lower rates of cerebral metabolism - peripheral insulin resistance attenuates cerebral metabolism more so in healthy younger than healthy older adults, and impairs working memory.

neuroscience↗