Advertisement

REGARDLESS OF THEIR LOCATION, WHITE MATTER HYPERINTENSITIES ARE ASSOCIATED WITH ADVANCED BRAIN AGING THROUGHOUT ADULTHOOD IN THE STUDY OF HEALTH IN POMERANIA

      Background

      White matter hyperintensities (WMH) have shown to be associated with increased risk of dementia. However, studies reporting the association of specific WMH locations with brain aging and dementia are scarce. We sought to investigate the association of WMH appearance in predefined anatomical brain regions and cardiovascular risk with brain atrophy patterns related to brain aging (BA), throughout adulthood in the general population, leveraging state of the art pattern analysis methods and structural equation modeling.

      Methods

      We delineated WMH using a fully automated segmentation method in a large population-based sample (n=2,367) covering most of the adulthood life span (range 20-90 years, median=53 years), from the Study of Health in Pomerania, Germany. We automatically quantified WMH volume within four anatomical WM regions of interest i) frontal, ii) parietal -temporal, iii) deep structures including fornix and internal capsule and iv) occipital, using a multi-atlas segmentation method. Using machine-learning methods, we calculated the SPARE-BA score, a subject-specific index that captures and quantifies age-related brain atrophy patterns. The Framingham cardiovascular disease risk score (CVD-RS) was used to summarize the individual cardiovascular risk profile. We used four structural equation models independently; we modelled the SPARE-BA index as dependent variable, age as independent variable as well as CVD-RS and WMH volume within each region of interest as mediators.

      Results

      Structural equation modeling showed that the age effect on brain aging patterns captured by the SPARE-BA score was mediated by WMH volume in frontal (8.7% Variance explained (VE), P<0.0001), parietal-temporal (9.5% VE, P<0.0001), deep WM structures including fornix and internal capsule (2.8%, VE, P<0.0001) and occipital (6.6% VE, P<0.0001) regions. The cardiovascular risk score was associated with WMH in frontal (P<0.0001), occipital (P<0.0001) and parietal-temporal (P<0.0001) regions but not in deep structures.

      Conclusions

      Our results indicate that, regardless of their location, WMH might accelerate the brain aging process throughout adulthood in the general population as a result of vascular risk factors, but also independent of them. Preventive strategies against WMH could help to delay brain aging.
      Figure thumbnail fx1
      Figure 1Four structural equation models showing potential causal association of regional WMH in the A) frontal, B) parietal -temporal, C) deep structures including fornix and internal capsule and D) occipital regions, with brain aging patterns of atrophy (SPARE-BA) across the adulthood life span from the SHIP sample (range 20-90 years, median = 53 years).