title: Long-term survival in adults 65 years and older with white matter hyperintensity: association with performance on the digit symbol substitution test.
abstract: OBJECTIVE
  White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST).
  
  
  METHODS
  Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58% women, 84% white) with WMH (0-9 points), DSST (0-90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5-18.1] years).
  
  
  RESULTS
  WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio [HR; 95% confidence interval {CI}] for WMH >3 points = 1.48 [1.35-1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27-1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95% CI] = 0.66 [0.55-0.81] and 0.72 [0.62-0.83], respectively).
  
  
  CONCLUSIONS
  WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA. rosanoc@edc.pitt.edu
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
authors.forename: Yue-Fang
authors.initials: YF
authors.lastname: Chang
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Studenski
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianaros
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.forename: William T
authors.initials: WT
authors.lastname: Longstreth
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008019:Life Style; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011930:Reaction Time / Q000502:physiology; D012737:Sex Factors; D020521:Stroke / Q000401:mortality; D017741:Survivors / Q000706:statistics & numerical data
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers
keywords: information processing; mortality; white matter hyperintensity