title: Influence of lifestyle modifications on age-related free radical injury to brain.
abstract: OBJECTIVE
  The Healthy Brain Initiative 2013-2018 seeks to optimize brain health as we age. Free radical injury is an important effector of molecular and cellular stress in the aging brain that derives from multiple sources.
  
  
  OBJECTIVE
  To identify potentially modifiable risk factors associated with increased markers of brain oxidative stress.
  
  
  METHODS
  This cross-sectional, academic multicenter study consisted of 320 research volunteers (172 women) aged 21 to 100 years who were medically healthy and cognitively normal.
  
  
  METHODS
  Free radical injury to the brain was assessed using cerebrospinal fluid (CSF) F2-isoprostane (F2-IsoP) concentrations correlated with age, sex, race, cigarette smoking, body mass index, inheritance of the ε4 allele of the apolipoprotein E gene (APOE), and CSF biomarkers of Alzheimer disease.
  
  
  RESULTS
  The concentration of CSF F2-IsoP increased with age by approximately 3 pg/mL (approximately 10%) from age 45 to 71 years in medically healthy, cognitively normal adults (P < .001). The CSF F2-IsoP concentration increased by approximately more than 10% for every 5-U increase in body mass index (P < .001). Current smoking had an approximately 3-fold greater effect on CSF F2-IsoPs compared with age (P < .001). Women had greater mean CSF F2-IsoP concentrations than men at all ages after adjusting for other factors (P = .02). Neither the concentration of CSF Alzheimer disease biomarkers nor inheritance of the APOE ε4 allele was associated with the CSF F2-IsoP concentration in this group of medically healthy, cognitively normal adults (P > .05). The association between CSF F2-IsoP concentrations and race was not significant after controlling for the effect of current smoking status (P = .45).
  
  
  CONCLUSIONS
  Our results are consistent with an age-related increase in free radical injury in the human brain and uniquely suggest that this form of injury may be greater in women than in men. Our results also highlighted 2 lifestyle modifications (ie, body mass index and smoking) that would have an even greater effect on suppressing free radical injury to the brain than would suppressing the processes of aging. These results inform efforts to achieve success in the Healthy Brain Initiative 2013-2018.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle2Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Shofer
authors.affiliation: Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Millard
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle2Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington3Department of Neurology, University of Washin.
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington5Department of Medicine, University of Washington, Seattle.
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle2Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland7Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center, Portland, Oregon.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.affiliation: Department of Pathology, University of Washington, Seattle.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015992:Body Mass Index; D001921:Brain / Q000378:metabolism*; D003430:Cross-Sectional Studies; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid*; D005260:Female; D005609:Free Radicals / Q000009:adverse effects*; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D028441:F2-Isoprostanes; D005609:Free Radicals