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Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study
Christopher B Brady1, J Michael Gaziano, Roberta A Cxypoliski
1Geriatric Research, Education, and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA 02130, USA. cbbrady@bu.edu
Insights
High-dose B vitamins did not improve cognitive function in patients with advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD), despite lowering homocysteine levels. Further research is needed to understand cognitive impairment in these populations.
Area of Science:
- Nephrology
- Neurology
- Nutritional Science
Background:
- Individuals with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) often exhibit elevated plasma total homocysteine (tHcy) levels.
- Elevated tHcy is a potential risk factor for cognitive impairment in this patient group.
- The efficacy of B vitamin supplementation in improving cognition in kidney disease patients remains undetermined.
Purpose of the Study:
- To investigate whether high-dose B vitamin treatment, aimed at reducing tHcy levels, can improve cognitive function in patients with advanced CKD and ESRD.
- To assess the impact of B vitamin supplementation on cognitive status over a one-year period in the studied population.
Main Methods:
- A randomized controlled trial involving 659 patients with advanced CKD or ESRD and high tHcy levels.
- Participants received daily high-dose B vitamins (folic acid, B6, B12) or a placebo for five years.
- Cognitive function was assessed at baseline and after one year of treatment using standardized tests.
Main Results:
- Approximately 19% of patients presented with cognitive impairment at baseline, irrespective of treatment or kidney disease status.
- B vitamin treatment successfully reduced tHcy levels by 26.7%.
- No significant improvement in initial cognitive outcomes or subsequent cognitive status was observed in the B vitamin group compared to the placebo group.
Conclusions:
- High-dose daily B vitamin supplementation, while effective in lowering tHcy levels, did not demonstrate a benefit for cognitive outcomes in patients with advanced CKD and ESRD.
- Limitations include the timing of cognitive assessments relative to treatment initiation and the overall scope of cognitive evaluation.
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 (> 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.
Intervention:
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.
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.
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