Brain Network Segregation and Glucose Energy Utilization: Relevance for Age-Related Differences in Cognitive Function

Abstract

The human brain is organized into segregated networks with strong within-network connections and relatively weaker between-network connections. This “small-world” organization may be essential for maintaining an energetically efficient system, crucial to the brain which consumes 20% of the body’s energy. Brain network segregation and glucose energy utilization both change throughout the lifespan. However, it remains unclear whether these processes interact to contribute to differences in cognitive performance with age. To address this, we examined fluorodeoxyglucose-positron emission tomography and resting-state functional magnetic resonance imaging from 88 participants aged 18–73 years old. Consistent with prior work, brain network segregation showed a negative association with age across both sensorimotor and association networks. However, relative glucose metabolism demonstrated an interaction with age, showing a negative slope in association networks but a positive slope in sensorimotor networks. Overall, brain networks with lower segregation showed significantly steeper age-related differences in glucose metabolism, compared with highly segregated networks. Sensorimotor network segregation mediated the association between age and poorer spatial cognition performance, and sensorimotor network metabolism mediated the association between age and slower response time. These data provide evidence that sensorimotor segregation and glucose metabolism underlie some age-related changes in cognition. Interventions that stimulate somatosensory networks could be important for treatment of age-related cognitive decline.

Shifted Dynamics of Glucose Metabolism in the Hippocampus During Aging

“…Since neurons require high energy consumption to function normally, notably to drive a sodium gradient across the cell membrane via the Na+/K+-ATPase, the cell's energy production capability is vital for the execution of brain physiological functions (Dienel, 2019 ). Although previous research demonstrates that energy metabolism is altered in the aged brain compared to the young adult brain, a more specific and quantitative description of energy metabolic pathways in the brain (Hoyer, 1990 ; Camandola and Mattson, 2017 ; Drulis-Fajdasz et al, 2018 ; Manza et al, 2020 ), especially in animals completing behavioral tasks, is not well-understood. Glucose is the major energy resource responsible for supporting brain activity under non-starvation conditions (Mergenthaler et al, 2013 ; Dienel, 2019 ).…”

Genetic variants link lower segregation of brain networks to higher blood pressure and worse cognition within the general aging population

“…High within-network connectivity but low betweennetwork connectivity, called system segregation, is a key global feature associated with higher cognitive performance across the life-span 3,4 . During aging and disease, system segregation decreases 3,[5][6][7][8][9] (for review see 10,11 ), resulting in poorer cognitive functions 3,5,9,[12][13][14]15 (for review see 4 ). In contrast, relatively preserved system segregation enhances cognitive resilience to brain alterations in older adults 16 .…”

Long-term prognosis and educational determinants of brain network decline in older adult individuals

“…This 'dedifferentiation' of functional systems has been associated with age-accompanied differences in patterns of brain activity, worse cognitive and motor ability, lower energy metabolism and altered neurotransmitter levels (for example, refs. [43][44][45][46][47] ). Cross-sectional comparisons have also revealed that middle-aged adults with lower socioeconomic status (SES) (35-64 years of age) exhibit lower brain system segregation than that of their peers of the same age with higher SES 48 , suggesting that there may exist environmental determinants of brain network aging.…”