title: Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study.
abstract: BACKGROUND
  Individuals with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) have high plasma total homocysteine (tHcy) levels, which may be a risk factor for cognitive impairment. Whether treatment with high-dose B vitamins to decrease high tHcy levels improves cognition in persons with kidney disease is unknown.
  
  
  METHODS
  Randomized controlled trial.
  
  
  METHODS
  A substudy of 659 patients (mean age, 67.3 +/- 11.7 years) who participated in a randomized double-blind clinical trial 5 years in duration conducted in 36 US Department of Veterans Affairs medical centers of the effect on all-cause mortality of vitamin-induced lowering of plasma tHcy level. 236 (35.8%) were treated by using dialysis (ESRD) and 423 (64.2%) had a Cockcroft-Gault estimated creatinine clearance of 30 mL/min or less (advanced CKD). All had high tHcy levels (> or =15 micromol/L) at baseline. Cognitive assessments began during the follow-up period of the main trial 3 years after treatment began; participants subsequently were retested 1 year later to assess cognitive change.
  
  
  METHODS
  Daily high-dose B vitamin capsule (40 mg of folic acid, 100 mg of vitamin B(6), and 2 mg of vitamin B(12)) or placebo.
  
  
  RESULTS
  Cognitive function at initial assessment and 1 year later.
  
  
  METHODS
  Telephone Interview of Cognitive Status-modified, supplemented with attention, working memory, and executive function tests.
  
  
  RESULTS
  Initial cognitive function was impaired in approximately 19% of patients regardless of treatment assignment (vitamin or placebo) or kidney disease status (advanced CKD or ESRD). Treatment decreased tHcy levels by 26.7%. Unadjusted and adjusted analyses showed that treatment did not improve initial cognitive outcomes or affect subsequent cognitive status 1 year later.
  
  
  CONCLUSIONS
  Cognitive assessments began after treatment was initiated; cognitive assessment was limited.
  
  
  CONCLUSIONS
  Treatment with high daily doses of B vitamins, which decreased tHcy levels, did not affect cognitive outcomes in patients with advanced CKD and ESRD.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA. cbbrady@bu.edu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Brady
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Cxypoliski
authors.forename: Peter D
authors.initials: PD
authors.lastname: Guarino
authors.forename: James S
authors.initials: JS
authors.lastname: Kaufman
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Warren
authors.forename: Pamela
authors.initials: P
authors.lastname: Hartigan
authors.forename: David S
authors.initials: DS
authors.lastname: Goldfarb
authors.forename: Rex L
authors.initials: RL
authors.lastname: Jamison
mesh_terms: D000367:Age Factors; D000368:Aged; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014481:United States; D014493:United States Department of Veterans Affairs; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex