title: Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility--Reykjavik Study.
abstract: BACKGROUND
  Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort.
  
  
  METHODS
  The analysis includes 3,543 men and women (born 1907-1935) participating in the Age, Gene, Environment Susceptibility-Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0-10) years, with 647 deaths. Cox regression was used to analyze the association of mortality to brain atrophy, adjusting for demographics, cardiovascular risk factors, and cerebral vascular disease.
  
  
  RESULTS
  Reduced risk of mortality was significantly associated with higher total brain volume (hazard ratio, 95% confidence interval = 0.71, 0.65-0.78), white matter (0.85, 0.78-0.93), total GM (0.74, 0.68-0.81), and cortical GM (0.78, 0.70-0.87). Overall, the associations were similar for cardiovascular and noncardiovascular-related deaths.
  
  
  CONCLUSIONS
  Independent of multiple risk factors and cerebral vascular damage, global brain volume predicts mortality in a large nondemented stroke-free community-dwelling older cohort. Total brain volume may be an integrated measure reflecting a range of health and with further investigation could be a useful clinical tool when assessing risk for mortality.
authors.affiliation: Department of Radiology, Leiden University Medical Centre, the Netherlands;
authors.forename: Saskia S G C
authors.initials: SS
authors.lastname: Van Elderen
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, Bethesda, Maryland;.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland;
authors.forename: Sigudur
authors.initials: S
authors.lastname: Sigurdsson
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, Bethesda, Maryland;.
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Haight
authors.affiliation: Department of Neurology, University of Pittsburgh, Pennsylvania;
authors.forename: Oscar
authors.initials: O
authors.lastname: Lopez
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland;
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.affiliation: Landspitali Hospital, Reykjavik, Iceland.
authors.forename: Palmi
authors.initials: P
authors.lastname: Jonsson
authors.affiliation: Department of Radiology, Leiden University Medical Centre, the Netherlands;
authors.forename: Laura
authors.initials: L
authors.lastname: de Jong
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, Bethesda, Maryland;.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, Bethesda, Maryland;.
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Icelandic Heart Association, Kopavogur, Iceland;
authors.forename: Vilmundar
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: Department of Radiology, Leiden University Medical Centre, the Netherlands;
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, Bethesda, Maryland;. launerl@nia.nih.gov.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002423:Cause of Death; D002561:Cerebrovascular Disorders / Q000453:epidemiology; D003710:Demography; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009026:Mortality; D009929:Organ Size; D016016:Proportional Hazards Models; D012307:Risk Factors; D013223:Statistics as Topic
keywords: Brain aging; Epidemiology; Mortality risking.; Neuroimaging