In a double-blind placebo-controlled study of 5-methyltetrahydrofolate (a form of folate), 50 mg/d, patients with dementia who were depressed experienced significant improvements in both mood and memory after 4 weeks of therapy.11 However, the relationship between cognitive functioning and folate remains unclear. A Cochrane systematic review of 4 controlled studies concluded that there is insufficient evidence to support the use of folic acid(Drug information on folic acid) with or without B12 as a treatment for dementia or other forms of severe cognitive impairment.12 Supplementation with large dosages of thiamine(Drug information on thiamine) (3 to 8 g/d) may result in mild improvement in cognitive impairment in patients with AD.13
A few small open studies have evaluated the efficacy of B12 as a cognition-enhancing agent in elderly patients who were moderately impaired and nondemented. Eighteen elderly patients with low serum B12 levels were given injections of B12 following a strict protocol: daily 1-mg injections for the first week, followed by weekly 1-mg injections for 1 month, then monthly 1-mg injections for 6 months. All patients in the study improved, and those who had been cognitively impaired for less than 1 year experienced the most significant gains.14
Vitamins C and E
These important antioxidants function as free-radical scavengers throughout the body and brain, possibly slowing progression of AD and other neurodegenerative diseases. The findings of a large epidemiologic study show a correlation between intake of vitamin C and E in the form of supplements and reduced risk of AD.15 This effect was greatest for vitamin E(Drug information on vitamin e).
Anecdotal reports suggest that supplementation with vitamins C and E improves cognitive functioning in patients with AD, but few controlled studies have been done, and the findings of observational studies are inconclusive or negative.16,17 A Cochrane review identified only one study of vitamin E in dementia that met rigorous inclusion criteria. That study failed to provide clear evidence of improved global or cognitive functioning or reduced behavioral disturbances in persons with moderate dementia.18
Combining vitamins E and C may reduce the prevalence and incidence of AD. A prospective 5-year study followed 4740 adults aged 65 and older.19 At the end of the study, there were 104 new cases of AD. A strong inverse correlation was found between the incidence and prevalence of AD and combined use of vitamin C (at least 500 mg/d) and vitamin E (at least 400 IU/d). However, there was no association between the use of vitamin C alone, vitamin E alone, or a multivitamin alone and the incidence or prevalence of AD. Large doses of vitamin E are associated with an increased risk of bleeding. Persons who are at increased risk of stroke should consult their physician before starting a high-dose vitamin E regimen.
Dehydroepiandros-terone (DHEA) is a precursor of testosterone and other hormones. DHEA binds to both g-aminobutyric acid receptors and N-methyl-d-aspartate receptors, but it is not clear whether these receptor affinities are related to its putative cognition-enhancing role.20 A Cochrane systematic review and meta-analysis found no support for the use of DHEA as a cognitive enhancer in healthy older persons.21 However, there is limited evidence that DHEA 200 mg/d may improve symptoms of cognitive impairment in patients with multi-infarct dementia.22 To date, no controlled trials have been done on DHEA in AD.
Limited evidence suggests that testosterone replacement therapy may improve global functioning in persons with mild AD. In a 6-month, randomized, double-blind, placebo-controlled study, 47 men aged 50 and older were randomized to receive testosterone 75 mg/d or placebo together with their usual medications. The study included healthy controls and patients with mild dementia. Global quality of life improved in both the mildly demented group and the healthy controls. Patients with mild dementia who received testosterone experienced less decline in overall functioning and visual-spatial abilities. Men who have benign prostatic hypertrophy or prostate cancer should avoid the use of testosterone.
Essential oils can be used as aromatherapy or applied directly to the skin during massage. Recent findings suggest that certain essential oils have beneficial calming effects on agitation in patients with dementia. A Cochrane systematic review found only 1 study that met inclusion criteria, and although the outcome of that study was positive, the reviewers concluded that methodologic problems limited the significance of its findings.23 In other studies, the essential oils of lemon balm and lavender reduced agitated behavior in persons with dementia when topically applied directly to the face and arms.24,25