Objective:

To investigate the age-dependent acceleration of white matter disease (WMD) volume progression across different age groups.

Background:

WMD is common among aging populations and is associated with adverse neurological outcomes. While age is a known risk factor for WMD burden, the precise relationship between age and the rate of WMD volume progression remains unclear.

Design/Methods:

This retrospective study included 2356 patients aged 40 years or older who underwent longitudinal MRI brain scans between 2011 and 2019 at Mayo Clinic. Baseline demographic and clinical characteristics, including vascular risk factors, were collected. The primary outcome was the annual rate of WMD volume progression, which was analyzed across the five age groups (40-49, 50-59, 60-69, 70-79, and 80-99 years). Analysis of Covariance (ANCOVA) assessed the effect of different age groups on WMD progression, while linear ridge regression was used to identify predictors of WMD progression.

Results:

The mean age of the cohort was 67.61 ± 11.45 years, with 52.7% female and 95.1% White. The baseline WMD volume averaged 13.05 ± 14.49 cm³, increasing to 18.30 ± 17.10 cm³ after a median follow-up of 4.78 years, corresponding to an annual progression rate of 1.19 ± 3.01 cm³/year. The annualized rate of WMD volume progression increased significantly with age, from 0.42 cc/year in the 40-49 age group to 1.65 cc/year in the 80-99 age group (p< 0.001). Additionally, the linear ridge regression model identified age, female sex, ever-smoker, diabetes, and baseline WMD volume as significant predictors of faster WMD progression (p<0.05).

Conclusions:

Our study revealed a significant age-dependent acceleration in WMD volume progression. Age, female sex, ever smoker, diabetes, and baseline WMD volume emerged as significant predictors of the rate of WMD volume progression.