Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort

Abstract

An individual's brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer's, dementia, and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972-73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.

Fig. 1. The distribution of chronological age and brain-age amongst the Dunedin Study members.

While there is very little variation in chronological age, there is a large amount of variation in brain-age.

Fig. 2. Associations betweeen brainAGE, cognitive function and biological aging.

a Associations between older age-45 brainAGE and lower cognitive function. The left panel displays the association between older brainAGE and lower childhood IQ. The right panel displays the association between older brainAGE and lower IQ measured at age 45. b Associations between older age-45 brainAGE and accelerated biological aging. The left panel displays the association between accelerated pace of biological aging between ages 26 and 45 and older brainAGE. The pace of aging quantifies study members’ rate of biological aging in year‐equivalent units of physiological decline occurring per chronological year. The average study member experienced 1 year of physiological decline per each chronological year, a pace of aging of 1. The right panel displays the association between older facial age and older brainAGE. To illustrate facial aging, the right panel shows digitally averaged faces of the ten male and female Study members rated as looking the oldest and the ten male and female Study members rated as looking the youngest. Facial Age is standardized to M = 0, SD = 1.

Fig. 3. The associations of brainAGE with cognitive functioning and cognitive decline.

Those with younger age-45 brainAGE had the highest IQ scores in both childhood and adulthood. In addition, cognitive decline was greatest among those with older age-45 brainAGE; the slopes connecting childhood to adulthood are steeper among Study members with older brainAGEs. Sample sizes for each decile from the lowest to the highest brainAGE were: 86, 86, 85, 86, 85, 86, 86, 85, 86, and 86.