Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. Enhancement of recovery from psychiatric illness by methylfolate.
The relevance of low folate levels as determinants of cognitive deficits and the usefulness of folate supplementation in the treatment of cognitive deficits was reviewed from the literature. Over 40 papers and book chapters published in English, French, German, Italian and Spanish were examined. This represents those papers published in the international literature in the last 10 years which were identified by various key words including folate, cognition and aging (or ageing). Among these papers, only 13 articles specifically addressed issues relevant to the criteria adopted for this review. The remaining papers were principally concerned with depression and or with other pathologies of the aged associated with folate deficiency. Although the specific role of low folate levels in the physiopathology of dementia is still under debate, a growing consensus is emerging in the literature where low folate as well as cobalamin levels in aged patients with cognitive deficits are being considered as a sign of functional problems in the absorption and utilization of vitamins, and not merely as a sign of bad eating habits. In studies where folate compounds were evaluated for treatment effects, the results of a majority of investigations indicated that folate treatment was effective in lessening cognitive deficits. Treatment efficacy, however, has not yet been sufficiently demonstrated by these results because there were no controlled studies and the methodology was heterogeneous for the evaluation of cognitive characteristics. An ad hoc double-blind, controlled versus placebo pilot study was undertaken to evaluate the efficacy of folic acid in 30 aged patients with abnormal cognitive decline and folate level below 3 ng/ml to better understand the value of this type of intervention. Our results from this preliminary study demonstrated that patients treated with folic acid for 60 days showed a significant improvement on both memory and attention efficiency when compared with a placebo group. The intensity of memory improvement was positively correlated with initial severity of folate deficiency. On the contrary, the severity of initial cognitive decline was unrelated to the degree of folate deficiency. Based on research demonstrating associations between folate, B-12 and B-6 vitamins and cognition and mood, we investigated the effects of short-term supplementation in 211 healthy younger, middle-aged and older women who took either 750 microg of folate, 15 microg of vitamin B-12, 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition, we examined associations between dietary intake of these vitamins and cognition and mood. Usual dietary intake status was estimated using a retrospective, self-report, quantified food frequency questionnaire. Participants completed alternate forms of standardized tests of cognitive processing resources, memory, executive function, verbal ability and self-report mood measures before and after supplementation. Supplementation had a significant positive effect on some measures of memory performance only, and no effect on mood. Dietary intake status was associated with speed of processing, recall and recognition and verbal ability. 41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.
The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.