Several clinical trials suggest that acetyl-L-carnitine delays onset of ARCD and improves overall cognitive function in the elderly. In a controlled clinical trial, acetyl-L-carnitine was given to elderly people with mild cognitive impairment. After 45 days of acetyl-L-carnitine supplementation at 1,500 mg per day, significant improvements in cognitive function (especially memory) were observed.¹⁶ Another large trial of acetyl-L-carnitine for mild cognitive impairment in the elderly found that 1,500 mg per day for 90 days significantly improved memory, mood, and responses to stress. The favorable effects persisted at least 30 days after treatment was discontinued.¹⁷ Controlled^18,19,20 and uncontrolled²¹ clinical trials on acetyl-L-carnitine corroborate these findings.

Most^{22,23,24,25,26,27,28,29} but not all³⁰ clinical trials, many of them double-blind, have found ginkgo supplementation to be a safe and effective treatment for ARCD.³¹

Animal studies have found the Ayurvedic herb bacopa has constituents that enhance several aspects of mental function and learning ability.^32,33,34 A controlled study found that a syrup containing an extract of dried bacopa herb given to children improved several measures of mental performance.³⁵ A double-blind trial in adults found that a standardized extract of bacopa (300 mg per day for people weighing under 200 lbs and 450 per day for people over 200 lbs) improved only one out of several measures of memory function after three months.³⁶ Another double-blind trial lasting twelve weeks found 300 mg per day of bacopa improved four out of fifteen measures of learning, memory, and other mental functions in adults.³⁷ A third double-blind trial found that 300 mg per day of bacopa improved memory acquisition and retention in healthy elderly people.³⁸ Similar results were found in a 12-week double-blind study of elderly individuals who had no evidence of dementia.³⁹ A fourth double-blind study found no effects on mental function in a group of healthy adults given 300 mg of standardized bacopa and tested two hours later. Bacopa has not been tested on people with memory problems.⁴⁰

In a double-blind trial, elderly people with high homocysteine levels received 800 mcg of folic acid per day or a placebo for three years. Compared with placebo, folic acid supplementation significantly slowed the rate of decline of memory and of other measures of cognitive function.⁴¹

Huperzine A, an isolated alkaloid from the Chinese medicinal herb huperzia(Huperzia serrata), has been found to improve cognitive function in elderly people with memory disorders. One double-blind trial found that huperzine A (100 to 150 mcg two to three times per day for four to six weeks) was more effective for improving minor memory loss associated with ARCD than the drug piracetam.⁴² More research is needed before the usefulness of huperzine A is confirmed for mild memory loss associated with ARCD.

Melatonin is a hormone secreted by the pineal gland in the brain. It is partially responsible for regulating sleep-wake cycles. Cognitive function is linked to adequate sleep and normal sleep-wake cycles. Cognitive benefits from melatonin supplementation have been suggested by preliminary research in a variety of situations and may derive from the ability of melatonin to prevent sleep disruptions.^43,44,45,46 A double-blind trial of ten elderly patients with mild cognitive impairment showed that 6 mg of melatonin taken two hours before bedtime significantly improved sleep, mood, and memory, including the ability to remember previously learned items.⁴⁷ However, in a double-blind case study of one healthy person, 1.6 mg of melatonin had no immediate effect on cognitive performance.⁴⁸

The long-term effects of regularly taking melatonin supplements remain unknown, and many healthcare practitioners recommend that people take no more than 3 mg per evening. A doctor familiar with the use of melatonin should supervise people who wish to take it regularly.

Phosphatidylserine (PS) derived from bovine brain phospholipids has been shown to improve memory, cognition, and mood in the elderly in at least two placebo-controlled trials. In both trials, geriatric patients received 300 mg per day of PS or placebo. In an unblinded trial of ten elderly women with depressive disorders, supplementation with PS produced consistent improvement in depressive symptoms, memory, and behavior after 30 days of treatment.⁴⁹ A double-blind trial of 494 geriatric patients with cognitive impairment found that 300 mg per day of PS produced significant improvements in behavioral and cognitive parameters after three months and again after six months.⁵⁰

Most research has been conducted with PS derived from bovine tissue, but what is available commercially is made from soy. The soy- and bovine-derived PS, however, are not structurally identical.⁵¹ Doctors and researchers have debated whether the structural differences could be important,^52,53 but so far only a few trials have studied the effects of soy-based PS.

Preliminary animal research shows that the soy-derived PS does have effects on brain function similar to effects from the bovine source.^54,51,56 An isolated, unpublished double-blind human study used soy-derived PS in an evaluation of memory and mood benefits in nondemented, nondepressed elderly people with impaired memories and accompanying depression.⁵⁷ In this three-month study, 300 mg per day of PS was not significantly more effective than a placebo. In a double-blind study, soy-derived PS was administered in the amount of 300 or 600 mg per day for 12 weeks to people with age-related memory impairment. Compared with the placebo, soy-derived PS had no effect on memory or on other measures of cognitive function.⁵⁸ While additional research needs to be done, currently available evidence suggests that soy-derived PS is not an effective treatment for age-related cognitive decline.

A double-blind trial found both 30 mg and 60 mg per day of vinpocetine improved symptoms of dementia in patients with various brain diseases.⁶⁰ Another double-blind trial gave 30 mg per day of vinpocetine for one month, followed by 15 mg per day for an additional two months, to people with dementia associated with hardening of the arteries of the brain, and significant improvement in several measures of memory and other cognitive functions was reported.⁶¹ Other double-blind trials have reported similar effects of vinpocetine in people with some types of dementia or age-related cognitive decline.^62,63 However, a study of Alzheimer patients in the United States found vinpocetine given in increasing amounts from 30 mg to 60 mg per day over the course of a year neither reversed nor slowed the decline in brain function measured by a number of different tests.⁶⁴

Vitamin B6 (pyridoxine) deficiency is common among people over age 65.⁶⁵ A Finnish study demonstrated that approximately 25% of Finnish and Dutch elderly people are deficient in vitamin B6 as compared to younger adults. In a double-blind trial, correcting this deficiency with 2 mg of pyridoxine per day resulted in small psychological improvements in the elderly group. However, the study found no direct correlation between amounts of vitamin B6 in the cells or blood and psychological parameters.⁶⁶ A more recent double-blind trial of 38 healthy men, aged 70 to 79 years, showed that 20 mg pyridoxine per day improved memory performance, especially long-term memory.⁶⁷

In a study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 5.4 years had no effect on cognitive function. However, supplementation appeared to prevent age-related cognitive decline in the 30% of women who had low dietary intake of B vitamins.⁶⁸

Supplementation with homocysteine-lowering B vitamins (folic acid, vitamin B12, and vitamin B6) also slowed the rate of brain atrophy in elderly people who had mild cognitive impairment and high homocysteine levels.⁶⁹

Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).⁷⁰ Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.

Caution: Synthetic beta-carotene has been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.

In a double-blind trial, supplementation with beta-carotene in the amount of 50 mg every other day for 18 years appeared to slow the loss of cognitive function in middle-aged healthy males. Short-term supplementation (one year) was not beneficial.⁷⁴

Use of vitamin C or vitamin E supplements, or both, has been associated with better cognitive function and a reduced risk of certain forms of dementia (not including Alzheimer’s disease).⁷⁵ Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.