Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders

Abstract

Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict "healthy" brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.

Figure 1

Distribution of brain age differences across the test cohort. Standard deviation is 3.72 years.

Figure 2

Age predicted by the deep neural network developed here, and linearly adjusted for age using coefficients calculated from the training set, plotted against calendar age for all participants in the test set. The diagonal line is y = x, or a perfect predictor. Colour indicates the density of the scatter with brighter being denser. The Pearson r is 0.82.

Figure 3

Regions of the brain highlighted by importance on age predictions from T1-weighted brain MRI. Each region (139 total) is overlaid with a constant color representing the decrease in accuracy the results from removing information in that region. Brighter color overlay indicates that a region was more salient to brain age differences as defined by permutation importance.

Figure 4

Manhattan type plot showing the significance of association (p-value) between 1,410 UK Biobank traits and brain age difference, coloured by trait category. The Bonferroni-corrected significance threshold is marked by a horizontal red line (p-value = 2.35 × 10^–5) and the 5% FDR correction threshold with a blue line (p-value = 1.45 × 10^–3). More details on significant traits is found in Table 1. Trait label 1: Time taken to start entering values in symbol-digit matching test, 2: Number of symbol digit matches made correctly, 3: Number of symbol digit matches attempted, 4: Multiple sclerosis, 5: Essential (primary) hypertension, 6: Diagnoses—secondary ICD10: Type 1 diabetes, 7: Type 2 diabetes, 8: Systolic brachial blood pressure during pulse wave analysis (PWA), 9: Central systolic blood pressure during PWA, 10: Cardiac index during PWA, 11: End systolic pressure during PWA, 12: Stroke volume during PWA, 13: Central augmentation pressure during PWA, 14: Cardiac output during PWA, 15: Central pulse pressure during PWA, 16: Peripheral pulse pressure during PWA, 17: Ventricular rate, 18: Diastolic blood pressure, 19: Body mass index (BMI), 20: Hand grip strength (left), 21: Hand grip strength (right), 22: Systolic blood pressure, 23: Taking insulin, 24: Number of treatments/medications taken.