Homocysteine Lowering and Cognition in CKD: The Veterans Affairs Homocysteine Study
Received 30 January 2009; accepted 26 May 2009. published online 24 July 2009.
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.
Study Design
Randomized controlled trial.
Setting & Participants
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 (≥15 μmol/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.
Intervention
Daily high-dose B vitamin capsule (40 mg of folic acid, 100 mg of vitamin B6, and 2 mg of vitamin B12) or placebo.
Outcomes
Cognitive function at initial assessment and 1 year later.
Measurements
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.
Limitations
Cognitive assessments began after treatment was initiated; cognitive assessment was limited.
Conclusion
Treatment with high daily doses of B vitamins, which decreased tHcy levels, did not affect cognitive outcomes in patients with advanced CKD and ESRD.
1Geriatric Research, Education, and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA
2Department of Neurology, Boston University School of Medicine, Boston, MA
3Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
4Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, MA
5Veterans Affairs Cooperative Studies Program Coordinating Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT
6Renal Section, Veterans Affairs Boston Healthcare System, Boston, MA
7Renal Section, Boston University School of Medicine, Boston, MA
8Veterans Affairs Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, New Mexico Veterans Affairs Health Care System, Albuquerque, NM
9College of Pharmacy, University of New Mexico, Albuquerque, NM
10Nephrology Section, New York Harbor Healthcare System, New York, NY
11New York University School of Medicine, New York, NY
12Veterans Affairs Palo Alto Health Care System, Palo Alto, CA
13Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
Address correspondence to Christopher B. Brady, PhD, GRECC(182), VA Boston Healthcare System, 150 S Huntington Ave, Boston, MA 02130
This is a US Government Work. There are no restrictions on its use.
Because an author of this manuscript is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Michael Shlipak, MD, MPH, University of California, San Francisco) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Editorial Policies section of the AJKD website.
ABSTRACT