Alzheimer’s Disease and Non-Alzheimer’s Dementia
  • Principal Proposed Natural Treatments
  • Other Proposed Natural Treatments
  • References
En Español (Spanish Version)

Alzheimer's disease is the most common cause of severe mental deterioration (dementia) in the elderly. It has been estimated that 30% to 50% of people over 85 years old suffer from this condition. Its cause is not known. However, microscopic examination of the brains of people who have died of Alzheimer’s shows loss of cells in the thinking part of the brain, particularly cells that release a chemical called acetylcholine.

Alzheimer's begins with subtle symptoms, such as loss of memory for names and recent events. It progresses from difficulty learning new information to a few eccentric behaviors to depression, loss of spontaneity, and anxiety. Over the course of the disease, the person gradually loses the ability to carry out the activities of everyday life. Disorientation, asking questions repeatedly, and an inability to recognize friends are characteristics of moderately severe Alzheimer's. Eventually, virtually all mental functions fail.

Similar symptoms may be caused by conditions other than Alzheimer's disease, such as multiple small strokes (called multi-infarct or vascular dementia), severe alcoholism, and certain more rare causes. It is very important to begin with an examination to discover what is causing the symptoms of mental decline. Various easily treatable conditions, such as depression, can mimic the symptoms of dementia.

Four drugs have shown at least modest benefit for Alzheimer's disease or non-Alzheimer's dementia: Reminyl, Exelon, Aricept, and Cognex. These medications usually produce a modest improvement in mild to moderate Alzheimer's disease by increasing the duration of action of acetylcholine. However, they can cause sometimes severe side effects due to the exaggeration of acetylcholine's action in other parts of the body.

Principal Proposed Natural Treatments
There are two natural treatments for Alzheimer's disease with significant scientific evidence behind them: ginkgo and phosphatidylserine . Huperzine A and vinpocetine , while more like drugs than natural remedies, may also improve mental function in people with dementia. Acetyl-L-carnitine was once considered a promising option for this condition as well, but current evidence suggests that it does not work.

The most well-established herbal treatment for Alzheimer's disease is the herb Ginkgo biloba . Numerous high quality double-blind, placebo-controlled studies indicate that ginkgo is effective for treating various forms of dementia. 1-4,76,79,80,83,91 A 1997 US trial enrolled more than 300 participants with Alzheimer’s disease or non-Alzheimer’s dementia. 80 Participants were given either 40 mg of Ginkgo biloba extract or placebo 3 times daily for a period of 52 weeks. The results showed significant but not entirely consistent improvements in the treated group.

Another study published in 2007 followed 400 people for 22 weeks, and used twice the dose of ginkgo employed in the study just described. 79 The results of this trial indicated that ginkgo was significantly superior to placebo. The areas in which ginkgo showed the most marked superiority as compared to placebo included, “apathy/indifference, anxiety, irritability/lability, depression/dysphoria and sleep/nighttime behavior.”

On the other hand, one fairly large study of ginkgo extract drew headlines for concluding that ginkgo is ineffective. 5 This 24-week, double-blind, placebo-controlled study of 214 participants with either mild to moderate dementia or ordinary age-associated memory loss found no effect with ginkgo extract at a dose of 240 mg or 160 mg daily. However, this study has been sharply criticized for a number of serious flaws in its design. 6 In another community-based study among 176 elderly subjects with early-stage dementia, researchers found no beneficial effect for 120 mg of ginko extract given daily for 6 months. 86

A 2011 systematic review of 9 placebo-controlled, randomized trials did find more promising evidence for ginkgo. 91 The trials, which involved 2,372 people with Alzheimer's disease or another form of dementia, ranged from 12-52 weeks. Those in the ginkgo group did have improvements in their cognition scores. A subgroup of people with Alzheimer's disease also showed improvements in their activities of daily living.

The ability of ginkgo to prevent or delay a decline in cognitive function is less clear. In a placebo-controlled trial of 118 cognitively intact adults 85 years or older, ginkgo extract seemed to effectively slow the decline in memory function over 42 months. The researchers also reported a higher incidence of stroke in the group that took ginkgo, a finding that requires more investigation. 82

In a 2009 review of 36 randomized trials involving 4,423 patients with declining mental function (including dementia), researchers concluded ginkgo appears safe. However, they also found inconsistent evidence regarding whether it works. 89

For more information, including dosage and safety issues, see the full Ginkgo article.

Phosphatidylserine (PS) is one of the many substances involved in the structure and maintenance of cell membranes. Double-blind studies involving a total of more than 1,000 people suggest that phosphatidylserine is an effective treatment for Alzheimer's disease and other forms of dementia.

The largest of these studies followed 494 elderly subjects in northeastern Italy over a course of 6 months. 7 All suffered from moderate to severe mental decline, as measured by standard tests. Treatment consisted of 300 mg daily of either PS or placebo. The group that took PS did significantly better in both behavior and mental function than the placebo group. Symptoms of depression also improved.

These results agree with those of numerous smaller double-blind studies involving a total of more than 500 people with Alzheimer's and other types of age-related dementia. 8-15

However, the form of phosphatidylserine available as a supplement has altered since the studies described above were performed, and the currently available form may not be equivalent. For more information, including dosage and safety issues, see the full Phosphatidylserine article.

Huperzine A
Huperzine A is a chemical derived from a particular type of club moss ( Huperzia serrata ). Like caffeine and cocaine, huperzine A is a medicinally active, plant-derived chemical that belongs to the class known as alkaloids. This substance is really more a drug than an herb, but it is sold over-the-counter as a dietary supplement for memory loss and mental impairment.

According to 3 Chinese double-blind trials enrolling a total of more than 450 people, use of huperzine A can significantly improve symptoms of Alzheimer’s disease and other forms of dementia. 32-34 However, one double-blind trial failed to find evidence of benefit, but it was a relatively small study. 35 In a review of 6 randomized controlled trials, researchers concluded that, on balance, huperzine A is probably of some benefit in Alzheimer’s disease, but the variable quality of these studies weakens this conclusion. 84

For more information, including dosage and safety issues, see the full Huperzine A article.

Vinpocetine is a chemical derived from vincamine, a constituent found in the leaves of common periwinkle ( Vinca minor ) as well as the seeds of various African plants. It is used as a treatment for memory loss and mental impairment.

Developed in Hungary more than 20 years ago, vinpocetine is sold in Europe as a drug under the name Cavinton. In the US, it is available as a so-called dietary supplement, although the substance probably does not fit that category by any rational definition. Vinpocetine does not exist to any significant extent in nature. Producing it requires significant chemical work performed in the laboratory.

Several double-blind studies have evaluated vinpocetine for the treatment of Alzheimer's disease and related conditions. 23,43-49 Unfortunately, most of these suffered from significant flaws in design and reporting. A review of the literature found three studies of acceptable quality, enrolling a total of 583 people. 23 Perhaps the best of these was a 16-week, double-blind, placebo-controlled trial of 203 people with mild to moderate dementia which found significant benefit in the treated group. 43 However, even this trial suffered from several technical limitations, and the authors of the review concluded that vinpocetine cannot yet be regarded as a proven treatment. Currently, several better quality trials are underway. 23

For more information, including dosage and safety issues, see the full Vinpocetine article.

Carnitine is a vitamin-like substance that is often used for angina, congestive heart failure, and other heart conditions. A special form of carnitine, acetyl-L-carnitine, has been extensively tested for the treatment of dementia: double- or single-blind studies involving a total of more than 1,400 people have been reported. 53-64,68

However, while early studies found evidence of modest benefit, two large and well-designed studies failed to find acetyl-L-carnitine effective at all. The first of these was a double-blind, placebo-controlled trial that enrolled 431 participants for 1 year. 65 Overall, acetyl-L-carnitine proved no better than placebo. However, because a close look at the data indicated that the supplement might help people who develop Alzheimer's disease at an unusually young age, researchers performed a follow-up trial. This 1-year, double-blind, placebo-controlled trial evaluated acetyl-L-carnitine in 229 patients with early-onset Alzheimer's. 64 Unfortunately, no benefits were seen here either.

One review of literature interpreted the cumulative results to mean that acetyl-L-carnitine may be mildly helpful for mild Alzheimer’s disease. 22 However, another review concluded that if acetyl-L-carnitine does offer benefits for any form of Alzheimer’s disease, they are too minor to make much of a practical difference. 21

For more information, including dosage and safety issues, see the full Carnitine article.

Other Proposed Natural Treatments
Two small double-blind studies performed by a single research group found evidence that the herbs sage20 and lemon balm19 can improve cognitive function in people with mild to moderate Alzheimer’s disease.

One study found that vitamin E (dl-alpha-tocopherol) may slow the progression of Alzheimer's disease, but another did not. 66,72 A very large study failed to find that use of vitamin E reduced risk of general mental decline (whether caused by Alzheimer’s or not) in women over 65. 75

Vitamins B6 , B12 , and folate have also been studied. Researchers found that daily intake of these vitamins did not improve cognitive ability in older men with high blood pressure, nor did it reduce the risk of dementia. 90

Very preliminary evidence suggests that N-acetylcysteine (NAC) might be helpful for slowing the progression of Alzheimer's disease. 67

Lavender oil used purely as aromatherapy (treatment involving inhaling essential oils) has been advocated for reducing agitation in people with dementia 52 ; however, people with dementia tend to lose their sense of smell, making this approach seem somewhat unlikely to work. 69 Topical use of essential oil of the herb lemon balm has also shown promise for reducing agitation in people with Alzheimer's disease 51 ; the researchers who tested it considered their method aromatherapy because the fragrance wafts up from the skin, but essential oils are also absorbed through the skin and this mechanism of action seems more plausible. Oral use of lemon balm extract has also shown promise. 70

As we explained at the beginning of this article, drugs used for Alzheimer’s disease affect levels of acetylcholine in the body. The body makes acetylcholine out of the nutrient choline. On this basis, supplements containing choline or the related substance phosphatidylcholine have been proposed for the treatment of Alzheimer’s disease, but the results of studies have not been positive. 24-28 One special form of choline, however, has shown more promise. In a 6-month, double-blind study of 261 people with Alzheimer’s disease, use of choline alfoscerate at a dose of 400 mg 3 times daily significantly improved cognitive function as compared to placebo. 18

Colistrinin, a substance derived from colostrum , has shown some promise for treatment of Alzheimer's. 71

Bee pollen , carnosine , citrulline , DMAE , 42,50inositol , magnesium , pregnenolone , vitamin B 1 , and zinc have also been suggested as treatments for Alzheimer's disease. However, as yet there is no reliable scientific evidence to support their use. Elevated blood levels of the substance homocysteine have been suggested as a contributor to Alzheimer's disease and multi-infarct dementia. However, a double-blind, placebo-controlled study failed to find that homocysteine-lowering treatment using B-vitamins was helpful for multi-infarct dementia. 73 Similarly, two studies failed to find benefits in people with Alzheimer’s disease. 81,88 In another study, a mixture of B-vitamins did not improve quality of life in people with mild cognitive impairment of various causes. 78 Early reports suggested that declining levels of the hormone DHEA cause impaired mental function in the elderly. On this basis, DHEA has been promoted as a cognition-enhancing supplement. However, the one double-blind study that tested DHEA for Alzheimer's disease found little to no benefit. 16,17

Studies of fish oil have failed to find it helpful for Alzheimer's disease, whether for delaying its onset, slowing its progression, or improving its symptoms. 74,77,87

In a sizable Danish trial, researchers investigated the effects of melatonin and light therapy (bright light exposure during daylight hours) on mood, sleep, and cognitive decline in elderly patients, most of whom suffered from dementia. 85 They found that melatonin 2.5 mg, given nightly for an average of 15 months, slightly improved quality of sleep, but it worsened mood. Melatonin apparently had no significant effect on cognition. On the other hand, light therapy alone slightly decreased cognitive and functional decline and improved mood. Combining melatonin with light therapy improved mood and quality of sleep. In a systematic review of 5 randomized trials including 323 people with dementia, researchers failed to find evidence that melatonin is helpful in enhancing memory and other cognitive abilities. 92 In 2 of the trials, however, melatonin was associated with short-term improvement in mood and behavior.

References Kleijnen J, Knipschild P. Ginkgo biloba.Lancet. 1992;340:1136-1139. Kanowski S, Herrmann WM, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996;29:47-56. Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Hum Psychopharmacol. 1994;9:215-222. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998. van Dongen MC, van Rossum E, Kessels AG, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183-1194. Le Bars P. Conflicting results on ginkgo research. Forsch Komplementarmed Klass Naturheilkd. 2002;9:19-20. Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano). 1993;5:123-133. Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, et al. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand. 1986;73:136-140. Engel RR, Satzger W, Gunther W, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol. 1992;2:149-155. Nerozzi D, Aceti F, Melia E, et al. Phosphatidylserine and memory disorders in the aged [in Italian; English abstract]. Clin Ther. 1987;120:399-404. Funfgeld EW, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer's type (SDAT). Prog Clin Biol Res. 1989;317:1235-1246. Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull. 1992;28:61-66. Amaducci L. Phosphatidylserine in the treatment of Alzheimer's disease: results of a multicenter study. Psychopharmacol Bull. 1988;24:130-134. Villardita C, Grioli S, Salmeri G, et al. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin Trials J. 1987;24:84-93. Palmieri G, Palmieri R, Inzoli MR, et al. Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin Trials J. 1987;24:73-83. Knopman D, Henderson VW. DHEA for Alzheimer's disease: a modest showing by a superhormone. Neurology. 2003;60:1060-1061. Wolkowitz OM, Kramer JH, Reus VI, et al. DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study. Neurology. 2003;60:1071-1076. De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25:178-193. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003;74:863-866. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther. 2003;28:53-59. Hudson S, Tabet N. Acetyl-l-carnitine for dementia. Cochrane Database Syst Rev. 2003;CD003158. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003;18:61-71. Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive impairment and dementia [review]. Cochrane Database Syst Rev. 2003;CD003119. Leathwood PD, Schlosser B. Phosphatidylcholine, choline and cholinergic function. Int J Vitam Nutr Res Suppl. 1986;29:49-67. Gauthier S, Bouchard R, Bacher Y, et al. Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Can J Neurol Sci. 1989;16:543-546. Etienne P, Dastoor D, Gauthier S, et al. Alzheimer disease: lack of effect of lecithin treatment for 3 months. Neurology. 1981;31:1552-1554. Weintraub S, Mesulan MM, Auty R, et al. Lecithin in the treatment of Alzheimer's disease. Arch Neurol. 1983;40:527-528. Heyman A, Schmechel D, Wilkinson W, et al. Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease. J Neural Transm Suppl. 1987;24:279-286. Zeisel SH. Dietary influences on neurotransmission. Adv Pediatr. 1986;33:23-47. Wurtman RJ, Growdon JH. Dietary enhancement of CNS neurotransmitters. Hosp Pract. 1978;13:71-77. Russell RW. Continuing the search for cholinergic factors in cognitive dysfunction. Life Sci. 1996;58:1965-1970. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao. 1995;16:391-395. Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders [in Chinese; English abstract]. Zhongguo Yao Li Xue Bao. 1991;12:250-252. Zhang Z, Wang X, Chen Q, et al. Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. Zhonghua Yi Xue Za Zhi. 2002;82:941-944. Xu SS, Cai ZY, Qu ZW, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao. 1999;20:486-490. Wood JL, Allison RG. Effects of consumption of choline and lecithin on neurological and cardiovascular systems. Fed Proc. 1982;41:3015-3021. Hirsch MJ, Growdon JH, Wurtman RJ. Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism. 1978;27:953-960. Davis KL, Berger PA. Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis. Biol Psychiatry. 1978;13:23-49. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr. 1992;11:473-481. Sanchez CJ, Hooper E, Garry PJ, et al. The relationship between dietary intake of choline, choline serum levels, and cognitive function in healthy elderly persons. J Am Geriatr Soc. 1984;32:208-212. Leathwood PD, Schlosser B. Phosphatidylcholine, choline and cholinergic function. Int J Vitam Nutr Res Suppl. 1986;29:49-67. Ferris SH, Sathananthan G, Gershon S, et al. Senile dementia: treatment with Deanol. J Am Geriatr Soc. 1977;25:241-244. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. 1991;6:31-43. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc. 1987;35:425-430. Dragunow M, Faull RL. Neuroprotective effects of adenosine. Trends Pharmacol Sci. 1988;9:193-194. Fenzl E, Apecechea M, Schaltenbrand R, et al. Efficacy and tolerance of vinpocetine administered intravenously, in addition of standard therapy, to patients suffering from an apoplectic insult. In: Krieglstein J, ed. Pharmacology of Cerebral Ischemia: Proceedings of the International Symposium on Pharmacology of Cerebral Ischemia. New York, NY: Elsevier Science Publishers; 1986: 430-434. Manconi E, Binaghi F, Pitzus F. A double-blind clinical trial of vinpocetine in the treatment of cerebral insufficiency of vascular and degenerative origin. Curr Ther Res Clin Exp. 1986;30:702-709. Cited by: Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. 1991;6:31-43. Peruzza M, DeJacobis M. A double-blind placebo controlled evaluation of the efficacy and safety of vinpocetine in the treatment of patients with chronic vascular or degenerative senile cerebral dysfunction. Adv Ther. 1986;3:201-209. Cited by: Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. 1991;6:31-43. Blaha L, Erzigkeit H, Adamczyk A, et al. Clinical evidence of the effectiveness of vinpocetine in the treatment of organic psychosyndrome. Hum Psychopharmacol. 1989;4:103-111. Cited by: Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. 1991;6:31-43. Fisman M, Mersky H, Helmes E. Double-blind trial of 2-dimethylaminoethanol in Alzheimer's disease. Am J Psychiaty. 1981;138:970-972. Ballard CG, O'Brien JT, Reichelt K, et al. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry. 2002;63:553-558. Holmes C, Hopkins V, Hensford C, et al. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry. 2002;17:305-308. Calvani M, Carta A, Caruso G, et al. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer's disease. Ann N Y Acad Sci. 1992;663:483-486. Cipolli C, Chiari G. Effects of L-acetylcarnitine on mental deterioration in the aged: initial results [in Italian; English abstract]. Clin Ther. 1990;132(suppl 6):479-509. Passeri M, Cucinotta D, Bonati, PA, et al. Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res. 1990;10:75-79. Salvioli G, Neri M. L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994;20:169-176. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology. 1991;41:1726-1732. Vecchi GP, Chiari G, Cipolli C, et al. Acetyl-L-carnitine treatment of mental impairment in the elderly: evidence from a multicenter study. Arch Gerontol Geriatr. 1991;2(suppl 2):159-168. Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996;47:705-711. Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl-levocarnitine in patients with Alzheimer's disease. Arch Neurol. 1992;49:1137-1141. Campi N, Todeschini GP, Scarzella L. Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. Clin Ther. 1990;12:306-314. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia. Curr Med Res Opin. 1990;11:638-647. Bonavita E. Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol. 1986;24:511-516. Thal LJ, Calvani M, Amato A, et al. A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology. 2000;55:805-810. Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996;47:705-711. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997;336:1216-1222. Stough C, Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants. Int J Neuropsychopharm. 2001;4:131-134. Hudson S, Tabet N. Acetyl-l-carnitine for dementia. Cochrane Database Syst Rev. 2003;CD003158. Snow LA, Hovanec L, Brandt J. A Controlled trial of aromatherapy for agitation in nursing home patients with dementia. J Altern Complement Med. 2004;10:431-437. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003;74:863-866. Bilikiewicz A, Gaus W. Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease. J Alzheimers Dis. 2004;6:17-26. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005 April 13. [Epub ahead of print] Stott DJ, Macintosh G, Lowe GD, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82:1320-1326. Freund-Levi YF, Eriksdotter-Jonhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD Study. Arch Neurol. 2006;63:1402-1408. Kang JH, Cook N, Manson J, et al. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2006;166:2462-2468. Napryeyenko O, Borzenko I. Ginkgo biloba special extract in dementia with neuropsychiatric features: a randomised, placebo-controlled, double-blind clinical trial. Arzneimittelforschung. 2007;57:4-11. Freund-Levi Y, Basun H, Cederholm T, et al. Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry. 2007 Jun 21. [Epub ahead of print] van Uffelen JG, Chin A Paw MJ, Hopman-Rock M, et al. The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial. Qual Life Res. 2007 Jul 7. [Epub ahead of print] Scripnikov A, Khomenko A, Napryeyenko O. Effects of Ginkgo biloba extract EGb 761® on neuropsychiatric symptoms of dementia: findings from a randomised controlled trial. Wien Med Wochenschr. 2007;157:295-300. Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997;278:1327-1332. Sun Y, Lu CJ, Chien KL, et al. Efficacy of multivitamin supplementation containing vitamins B(6) and B(12) and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in taiwanese patients. Clin Ther. 2007;29:2204-2214. Dodge HH, Zitzelberger T, Oken BS, et al. A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline. Neurology. 2008 Feb 27. Bornhoft G, Maxion-Bergemann S, Matthiessen PF. External validity of clinical trials for treatment of dementia with ginkgo biloba extracts.] Z Gerontol Geriatr. 2008 Mar 11. Li J, Wu HM, Zhou RL, Liu GJ, Dong BR. Huperzine A for Alzheimer's disease. Cochrane Database of Systematic Reviews. 2008;(2):CD005592. Riemersma-van der Lek RF, Swaab DF, Twisk J, et al. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299:2642-2655. McCarney R, Fisher P, Iliffe S, et al. Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial. Int J Geriatr Psychiatry. 2008 Jun 9. Jia X, McNeill G, Avenell A. Does taking vitamin, mineral and fatty acid supplements prevent cognitive decline? A systematic review of randomized controlled trials. J Hum Nutr Diet. 2008;21:317-336. Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300:1774-1783. Birks J, Evans JG. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews. 2009;(1):CD003120. Ford AH, Flicker L, Alfonso H, et al. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology. 2010;75(17):1540-1547. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010;10:14. Jansen S, Forbes D, Duncan V, Morgan D, Malouf R. Melatonin for the treatment of dementia. Cochrane Database Syst Rev. 2011;(1):CD003802.
Last Reviewed August 2013

Health Information Library content is provided by EBSCO Publishing, fully accredited by URAC. URAC is an independent, nonprofit health care accrediting organization dedicated to promoting health care quality through accreditation, certification and commendation.


This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.


To send comments or feedback to EBSCO's Editorial Team regarding the content please e-mail