The 'middle-aging' brain

• Published in: Trends in neurosciences (Regular ed.) Vol. 47; no. 4; pp. 259 - 272
• Main Authors: Dohm-Hansen, Sebastian, English, Jane A., Lavelle, Aonghus, Fitzsimons, Carlos P., Lucassen, Paul J., Nolan, Yvonne M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2024
• Subjects: cognition; inflammation; machine learning; neurodegeneration; neuroimaging; omics; neurodegeneration; omics; cognition; machine learning; inflammation; neuroimaging
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2024.02.001

Middle age (roughly the fifth and sixth decades of human life) has historically been understudied compared to more advanced age, but is emerging as marking a possible shift in brain aging that is predictive of future cognitive health, while still being amenable to intervention.Some age-related changes of the brain display approximately linear trajectories throughout adult life, whereas others change non-linearly in a life stage-specific manner. Middle age features accelerating changes in gait, reaction time, memory, functional connectivity, white matter integrity, and neuroinflammation, as well as in gene and protein expression.Aging processes in systems and organs other than the brain (such as the systemic circulation) impact upon brain aging and could even accelerate it.In females, menopause is a defining feature of middle age that is associated with non-linear changes of the brain, some of which have implications for cognitive aging.
Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan.
Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan.