June 2002
E H Reynolds
It is becoming clear that folic acid affects mood and cognitive function, especially in older people. Edward Reynolds draws together the evidence
Folic acid is important for functioning of the nervous system at all ages. In the fetus the relation between maternal folate status and the risk of neural tube defects is well established: clinical trials have shown that periconceptual preventive treatment with 400 μg or higher of folic acid significantly reduces the risks of such defects.
In neonates, infants, children, and adolescents, inborn errors of folate transport and metabolism are associated with a variety of overlapping syndromes which are influenced by age of clinical presentation. These include developmental delay, cognitive deterioration, motor and gait abnormalities, behavioural or psychiatric symptoms, seizures, signs of demyelination or failure of myelination, and vascular changes seen on magnetic resonance imaging or postmortem examination. Less commonly, subacute combined degeneration and peripheral neuropathy may also occur.
In adult patients presenting with megaloblastic anaemia due to folate deficiency, approximately two thirds have neuropsychiatric disorders which overlap considerably with those associated with anaemia due to vitamin B-12 deficiency. However, depression is commoner in patients with folate deficiency, and subacute combined degeneration with peripheral neuropathy is more frequent in those with vitamin B-12 deficiency.
The degree of anaemia is poorly correlated with the presence of neuropsychiatric disorders, but if these anaemias were left untreated nearly all patients would eventually develop neuropsychiatric complications.
Over the past 35 years numerous studies have shown a high incidence of folate deficiency correlated with mental symptoms, especially depression and cognitive decline in epileptic, neurological, psychiatric, geriatric, and psychogeriatric populations.
Furthermore, recent studies in elderly people suggest a link between folic acid, homocysteine, ageing, depression, and dementia, including Alzheimer's disease and vascular disease.
In this paper I review the evidence relating folate deficiency to depression and dementia, especially in the ageing nervous system.
