Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study

• Published in: American journal of kidney diseases Vol. 54; no. 3; p. 440
• Main Authors: Brady, Christopher B, Gaziano, J Michael, Cxypoliski, Roberta A, Guarino, Peter D, Kaufman, James S, Warren, Stuart R, Hartigan, Pamela, Goldfarb, David S, Jamison, Rex L
• Format: Journal Article
• Language: English
• Published: United States 01.09.2009
• Subjects: Age Factors; Aged; Cognition - drug effects; Cognition - physiology; Cognition Disorders - blood; Cognition Disorders - drug therapy; Cognition Disorders - etiology; Double-Blind Method; Female; Follow-Up Studies; Homocysteine - blood; Humans; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - drug therapy; Male; Middle Aged; Risk Factors; United States; United States Department of Veterans Affairs; Vitamin B Complex - therapeutic use; United States
• ISSN: 1523-6838
• DOI: 10.1053/j.ajkd.2009.05.013

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. Randomized controlled trial. 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. 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. Cognitive function at initial assessment and 1 year later. Telephone Interview of Cognitive Status-modified, supplemented with attention, working memory, and executive function tests. 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. Cognitive assessments began after treatment was initiated; cognitive assessment was limited. Treatment with high daily doses of B vitamins, which decreased tHcy levels, did not affect cognitive outcomes in patients with advanced CKD and ESRD.