title: Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men.
abstract: BACKGROUND
  High serum homocysteine (HCY) levels have been associated with thromboembolic cerebrovascular disease, but their relationship to microvascular disease is uncertain. Homocysteine also has a direct neurotoxic effect and has been linked to brain atrophy and an increased risk of Alzheimer disease.
  
  
  OBJECTIVE
  To examine the relationship of HCY levels to brain and cognitive measures in a healthy community sample.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Individuals residing in Canberra and Queanbeyan, Australia, who were participating in the longitudinal PATH Through Life Project.
  
  
  METHODS
  Individuals aged 60 to 64 years selected randomly from the community, 196 men and 189 women.
  
  
  METHODS
  Regression coefficients with HCY level as the putative determinant and various magnetic resonance imaging measures (brain atrophy index, ventricle-brain ratios, volume of periventricular and deep white matter hyperintensities) and cognitive measures (information processing speed, verbal memory, fine motor speed) as dependent measures.
  
  
  RESULTS
  Homocysteine levels did not have a significant relationship with brain atrophy index or ventricle-brain ratios. High HCY levels were related to increased deep white matter hyperintensities but not periventricular white matter hyperintensities, after correcting for levels of folate, vitamin B(12), creatinine, and thyrotropin; hypertension; smoking; and diabetes, the relationship being significant only in men. Homocysteine levels were related to impairment in verbal memory and fine motor speed but not after the previously mentioned correction.
  
  
  CONCLUSIONS
  Total HCY level is independently related to leukoaraiosis in middle-aged men, and this may be functionally relevant in the form of mild cognitive impairment. The remediation of hyperhomocysteinemia should begin early in life if its deleterious effects on the brain are to be prevented.
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, Australia. p.sachdev@unsw.edu.au
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.forename: Ruth
authors.initials: R
authors.lastname: Parslow
authors.forename: Chris
authors.initials: C
authors.lastname: Salonikas
authors.forename: Ora
authors.initials: O
authors.lastname: Lux
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.forename: Daya
authors.initials: D
authors.lastname: Naidoo
authors.forename: Helen
authors.initials: H
authors.lastname: Christensen
authors.forename: Anthony
authors.initials: A
authors.lastname: Jorm
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology* / Q000502:physiology; D001927:Brain Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011859:Radiography; D012044:Regression Analysis; D012737:Sex Factors
chemical_list: D006710:Homocysteine