When Age Is More Than a Number: Acceleration of Brain Aging in Neurodegenerative Diseases.

Aging of the brain is characterized by deleterious processes at various levels including cellular/molecular and structural/functional changes. Many of these processes can be assessed in vivo by means of modern neuroimaging procedures, allowing the quantification of brain age in different modalities. Brain age can be measured by suitable machine learning strategies. The deviation (in both directions) between a person's measured brain age and chronologic age is referred to as the brain age gap (BAG). Although brain age, as defined by these methods, generally is related to the chronologic age of a person, this relationship is not always parallel and can also vary significantly between individuals. Importantly, whereas neurodegenerative disorders are not equivalent to accelerated brain aging, they may induce brain changes that resemble those of older adults, which can be captured by brain age models. Inversely, healthy brain aging may involve a resistance or delay of the onset of neurodegenerative pathologies in the brain. This continuing education article elaborates how the BAG can be computed and explores how BAGs, derived from diverse neuroimaging modalities, offer unique insights into the phenotypes of age-related neurodegenerative diseases. Structural BAGs from T1-weighted MRI have shown promise as phenotypic biomarkers for monitoring neurodegenerative disease progression especially in Alzheimer disease. Additionally, metabolic and molecular BAGs from molecular imaging, functional BAGs from functional MRI, and microstructural BAGs from diffusion MRI, although researched considerably less, each may provide distinct perspectives on particular brain aging processes and their deviations from healthy aging. We suggest that BAG estimation, when based on the appropriate modality, could potentially be useful for disease monitoring and offer interesting insights concerning the impact of therapeutic interventions.