title: Lower microstructural integrity of brain white matter is related to higher mortality.
abstract: 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.
authors.affiliation: From 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.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: From 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.
authors.forename: Lotte G M
authors.initials: LG
authors.lastname: Cremers
authors.affiliation: From 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.
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.affiliation: From 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.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From 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.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: From 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.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: From 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.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: From 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.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: From 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.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From 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. m.vernooij@erasmusmc.nl.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000368:Aged; D016880:Anisotropy; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000401:mortality*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology*; D018672:Community Health Planning; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009426:Netherlands; D066127:White Matter / Q000000981:diagnostic imaging*