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Folate in dementia and cognitive dysfunction

An association between serum tHcy concentration or B-vitamins levels and the cognitive performance has been observed in clinical trials with dementia free subjects at baseline (1). Low folate status and HHCY are associated with a higher prevalence of cognitive impairment or Alzheimer’s disease. In a recent meta-analysis involving > 8,600 participants (mean age range: 47 – 81 years, mean study duration: 5 years) of 8 cohort studies Wald et al. reported a significant association between serum tHcy and the incidence of dementia (2). The OR for a 5 μmol/L increase in serum tHcy was 1.35 (95% CI = 1.02 – 1.79) while the OR for a 3 μmol/L decrease in serum tHcy (the average reduction expected using FA and B12 supplements) was 0.78 (95% CI = 0.66 – 0.93) (2). A prospective study on elderly subjects (> 70 years) has shown that low folate or B12 were associated with doubling the risk of Alzheimer's disease (3).

Mild cognitive impairment (MCI) is common (14 – 18%) in elderly people (> 70 years). Fifty percent of people with MCI can develop Alzheimer’s disease or other forms of dementia within 5 years (4). Moreover, tHcy-lowering by B-vitamins (0.8 mg FA, 0.5 mg B12, and 20 mg B6) slowed the rate of accelerated brain atrophy in elderly with MCI (5). In a recent randomized controlled trial on participants (age: ≥ 70 years) with MCI 133 participants were supplemented with 0.8 mg FA, 0.5 mg B12, and 20 mg B6 and 133 participants received placebo for 2 years (6). The supplementation with B-vitamins appeared to slow the cognitive decline in the elderly with MCI, particularly in those with elevated tHcy.


1.     Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476-83.
2.     Wald DS, Kasturiratne A, Simmonds M. Serum homocysteine and dementia: Meta-analysis of eight cohort studies including 8669 participants. Alzheimers Dement 2011;7:412-7.
3.     McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C. Homocysteine and cognitive decline in healthy elderly. Dement Geriatr Cogn Disord 2001;12:309-13.
4.     DeCarli C. Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol 2003;2:15-21.
5.     Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE 2010;5:e12244.
6.     de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 2012;27:592-600.