Prediction of brain age and cognitive age: Quantifying brain and cognitive maintenance in aging

Abstract

The concept of brain maintenance refers to the preservation of brain integrity in older age, while cognitive reserve refers to the capacity to maintain cognition in the presence of neurodegeneration or aging-related brain changes. While both mechanisms are thought to contribute to individual differences in cognitive function among older adults, there is currently no "gold standard" for measuring these constructs. Using machine-learning methods, we estimated brain and cognitive age based on deviations from normative aging patterns in the Whitehall II MRI substudy cohort (N = 537, age range = 60.34-82.76), and tested the degree of correspondence between these constructs, as well as their associations with premorbid IQ, education, and lifestyle trajectories. In line with established literature highlighting IQ as a proxy for cognitive reserve, higher premorbid IQ was linked to lower cognitive age independent of brain age. No strong evidence was found for associations between brain or cognitive age and lifestyle trajectories from midlife to late life based on latent class growth analyses. However, post hoc analyses revealed a relationship between cumulative lifestyle measures and brain age independent of cognitive age. In conclusion, we present a novel approach to characterizing brain and cognitive maintenance in aging, which may be useful for future studies seeking to identify factors that contribute to brain preservation and cognitive reserve mechanisms in older age.

Keywords: aging; brain maintenance; cognitive reserve; lifestyle; machine learning; neuroimaging; trajectories.

FIGURE 1

Conceptual illustration of brain age (left) and cognitive age (right), where the distance between estimated brain age/cognitive age (colored dots) and the expected brain age/cognitive age (black line) represents brain age gap (BAG) and cognitive age gap (CAG)

FIGURE 2

An overview of the variables of interest provided at each phase of the WHII study (for a full description of data available at all study phases, please see https://www.ucl.ac.uk/epidemiology‐health‐care/research/epidemiology‐and‐public‐health/research/whitehall‐ii/data‐collection). Phases were selected based on the availability of measures of alcohol consumption, smoking habits, and physical activity. Composite measures of healthy lifestyle scores were derived from five phases (average length of time [mean ± SD] = 16.3 years ± 1.4), with an MRI scan administered at the fifth timepoint

FIGURE 3

Trajectories of the three‐class solution that was identified as the best fit, which are described in Section 3.3. Shaded areas reflect 95% confidence intervals