Normative values of the brain health index in UK biobank

Background

The Brain Health Index (BHI) is an automated approach to quantifying brain integrity, combining different types of structural magnetic resonance imaging (MRI). Normative values derived from generally healthy individuals provide a vital baseline for understanding neurodegenerative change. Although commonplace in other areas of medicine, these are not always established when proposing new analytical approaches using MRI. The scale and quality of the UK Biobank imaging cohort (approximately N = 50k, as of 2022) allows for derivation of such values, and the wealth of additional lifestyle, physiological and demographic data enables validation of BHI through comparison with more established variables which may affect brain health.

Aim

This study aimed to: 1) establish normative BHI values in a cohort of ‘healthy’ participants, and 2) explore associations between BHI and risk factors for brain health.

Methods

The BHI was computed using voxel-based Gaussian mixture model cluster analysis of T1 and T2 FLAIR MRI in a sub-cohort of UK Biobank participants. From these data, normative score curves – with bounds described as 1, 2 and 3 standard deviations from the mean – were produced for males and females, using regression analyses to measure the scale of the BHI values as a function of age. Additional Pearson’s correlation testing was used to examine known risk factors to brain health and their relationship to BHI scores, with t-tests and ANOVAs used to determine between-group differences in BHI scoring.

Results

Data from 2,990 participants (50.07% male, 97.05% Caucasian, 43.6% with degree-level education) were used to derive normative BHI curves from 48 to 77 years old. BHI scores were higher in female than male participants (95% CI: 0.0103 to 0.0162, p <0.001, Cohen’s d = 0.0416), males with a degree (95% CI: 0.000 to 0.009; p < 0.05; Cohen’s d = 0.044), and lower in people with type 2 diabetes mellitus (95% CI: 0.018 to 0.033; p <0.001; Cohen’s d = 0.0417), hypertension (95% CI: 0.008 to 0.018; p <0.001; Cohen’s d = 0.0419), and regular smokers (95% CI: 0.009 to 0.017, p <0.001, Cohen’s d = 0.041). BHI scores were higher in those with lower waist-to-hip ratios (WHR; males: R² = 0.02121, F(1, 1466) = 31.77, p <0.001; females: R² = 0.02201, F(1, 1454) = 32.72, p <0.001), and lower pulse pressure (males: R² = 0.06261, F(1, 1215) = 81.16, p <0.001; females: R² = 0.07616, F(1, 1205) = 99.34, p <0.001).

Conclusions

BHI score curves may provide useful reference values for future clinical research. More work is required to determine normative values in more diverse populations.