A Cochrane review (abstract , review [Abstract]) included 8 studies with a total of 1 523 patients. Four trials enrolled healthy older people, and four recruited participants with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Two studies involved a combination of folic acid and vitamin B12. Pooling the data was not possible owing to heterogeneity. There was no adequate evidence of benefit from folic acid supplemententation with or without vitamin B12 on cognitive function and mood of unselected healthy elderly people. However, in one trial enrolling a selected group of healthy elderly people with high homocysteine levels (n=818), 800 µg/day folic acid supplementation over three years was associated with significant benefit in terms of global functioning (WMD 0.05, 95% CI 0.004 to 0.096); memory storage (WMD 0.14, 95% CI 0.04 to 0.24) and information-processing speed (WMD 0.09, 95% CI 0.02 to 0.16). .
In one pilot trial enrolling people with Alzheimer's disease, the overall response to cholinesterase inhibitors significantly improved with folic acid at a dose of 1 mg/day (OR 4.06, 95% CI 1.22 to 13.53) and there was a significant improvement in scores on the Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients (WMD 4.01, 95% CI 0.50 to 7.52). Other trials involving people with cognitive impairment did not show any benefit in measures of cognitive function from folic acid, with or without vitamin B12. Folic acid plus vitamin B12 was effective in reducing serum homocysteine concentrations (WMD -5.90, 95% CI -8.43 to -3.37). Folic acid was well tolerated and no adverse effects were reported.
Comment: The quality of evidence is downgraded by indirectness (the range of folic acid dosage may have been too low; some outcome measures may have been affected by learning from repetition; participants with cognitive impairment or dementia were heterogeneous) and by imprecise results (limited study size for each comparison). In only one small trial a low folate level was used as inclusion criteria. There is no data on the effectiveness of vitamin B12 in patients with low levels of this vitamin.
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