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Published on: May 19, 2015
Lower microstructural integrity of brain white matter is related to higher mortality
Sanaz Sedaghat1, Lotte G M Cremers1, Marius de Groot1
1From the Departments of Epidemiology (S.S., L.G.M.C., M.d.G., A.H., O.H.F., A.D., M.A.I., M.W.V.), Radiology (L.G.M.C., M.d.G., A.v.d.L., W.J.N., M.A.I., M.W.V.), Medical Informatics (M.d.G., W.J.N.), and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam; and Imaging Science and Technology (W.J.N.), Faculty of Applied Sciences, Delft University of Technology, the Netherlands.
Objective:
To investigate the association of cerebral white matter microstructural integrity with mortality.
Methods:
We included 4,294 individuals, free from stroke and dementia (mean age 63.6 years, 44% male) from the population-based Rotterdam Study (2006-2011). Diffusion-MRI was used to assess the microstructural integrity of the white matter, both globally and for specific white matter tracts. Fractional anisotropy and mean diffusivity were the measures used to quantify white matter integrity. All-cause mortality and cause-specific mortality was recorded with a median follow-up time of 5.4 and 4.6 years, respectively. Cox regression models, adjusted for age, sex, APOE ε4 allele carriership, cardiovascular risk factors, and macrostructural MRI changes, were used to estimate hazard ratios.
Results:
During the follow-up time, 216 participants (5.0%) died of all causes, 31 (0.7%) of cardiovascular causes, and 102 individuals (2.4%) died of noncardiovascular causes. Each SD decrease in fractional anisotropy and each SD increase in mean diffusivity was associated with a 1.37-fold (95% confidence interval: 1.20-1.57) and a 1.49-fold (95% confidence interval: 1.28-1.75) higher hazard of all-cause mortality, respectively. The associations were more prominent with cardiovascular mortality than with noncardiovascular mortality. In tract-specific analyses, we observed that association tracts were more prominently related to mortality.
Conclusions:
Our findings suggest that impairments in cerebral white matter, even at early stages, are not limited to adverse brain outcomes and they are related to mortality, especially from cardiovascular causes.
Insights
Reduced white matter integrity, indicated by lower fractional anisotropy and higher mean diffusivity, is linked to increased mortality risk. This association is particularly strong for cardiovascular causes of death, highlighting brain health
Area of Science:
- Neuroimaging
- Epidemiology
- Gerontology
Background:
- Cerebral white matter integrity is crucial for cognitive function.
- Age-related white matter changes are common but their association with mortality is not fully understood.
Purpose of the Study:
- To investigate the association between cerebral white matter microstructural integrity and all-cause and cause-specific mortality.
- To determine if white matter integrity predicts mortality risk, independent of other risk factors.
Main Methods:
- Utilized diffusion magnetic resonance imaging (dMRI) to assess white matter integrity (fractional anisotropy, mean diffusivity) in 4,294 participants from the population-based Rotterdam Study.
- Followed participants for mortality (all-cause, cardiovascular, noncardiovascular) using Cox regression models, adjusting for relevant covariates.
- Analyzed global and tract-specific white matter integrity in relation to mortality outcomes.
Main Results:
- A decrease in fractional anisotropy and an increase in mean diffusivity were significantly associated with a higher hazard of all-cause mortality.
- These associations were more pronounced for cardiovascular mortality compared to noncardiovascular mortality.
- Tract-specific analyses revealed that association tracts were more strongly related to mortality risk.
Conclusions:
- Impaired cerebral white matter microstructural integrity, even in early stages, is associated with increased mortality risk.
- White matter integrity is a predictor of mortality, particularly from cardiovascular causes.
- These findings underscore the systemic implications of brain health beyond neurological outcomes.
