Vitamins that may be helpful
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.28 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.29 Controlled30 31 32 and uncontrolled33 clinical trials on acetyl-L-carnitine corroborate these findings.
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.34 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.35
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.36 Doctors and researchers have debated whether the structural differences could be important,37 38 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the soy-derived PS does have effects on brain function similar to effects from the bovine source.39 40 41 An isolated, unpublished double-blind human study used soy-derived PS in an evaluation of memory and mood benefits in nondemented, nondepressed elderly people with impaired memories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.42 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.43 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.
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.44 Whether folic acid would slow cognitive decline in people with normal homocysteine levels is not known.
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.45 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.46 Other double-blind trials have reported similar effects of vinpocetine in people with some types of dementia or age-related cognitive decline.47 48 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.49
Vincamine, the unmodified compound found naturally in Vinca minor, has also been tested in people with dementia. A large double-blind trial found 60 mg per day of vincamine was more effective than placebo for improving several measures of cognitive function in patients with either Alzheimer’s disease or dementia associated with vascular brain disease.50 A small double-blind study of vascular dementia also reported benefits using 80 mg per day of vincamine.
Vitamin B6 (pyridoxine) deficiency is common among people over age 65.51 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.52 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.53
Supplementation with vitamin B12 may improve cognitive function in elderly people who have been diagnosed with a B12 deficiency. Such a deficiency in older people is not uncommon. In a preliminary trial, intramuscular injections of 1,000 mcg of vitamin B12 were given once per day for a week, then weekly for a month, then monthly thereafter for 6 to 12 months. Researchers noted “striking” improvements in cognitive function among 22 elderly people with vitamin B12 deficiency and cognitive decline.54 Cognitive disorders due to vitamin B12 deficiency may also occur in people who do not exhibit the anemia that often accompanies vitamin B12 deficiency. For example, in a study of 141 elderly people with cognitive abnormalities due to B12 deficiency, 28% had no anemia. All participants were given intramuscular injections of vitamin B12, and all showed subsequent improvement in cognitive function.55
Vitamin B12 injections put more B12 into the body than is achievable with absorption from oral supplementation. Therefore, it is unclear whether the improvements in cognitive function described above were due simply to correcting the B12 deficiency or to a therapeutic effect of the higher levels of vitamin B12 obtained through injection. Elderly people with ARCD should be evaluated by a healthcare professional to see if they have a B12 deficiency. If a deficiency is present, the best way to proceed would be initially to receive vitamin B12 injections. If the injections result in cognitive improvement, some doctors would then recommend an experimental trial with high amounts of oral B12, despite a current lack of scientific evidence. If oral vitamin B12 is found to be less effective than B12 shots, the appropriate treatment would be to revert to injectable B12. At present, no research trials support the use of any vitamin B12 supplementation in people who suffer from ARCD but are not specifically deficient in vitamin B12.
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.56 57 58 59 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.60 However, in a double-blind case study of one healthy person, 1.6 mg of melatonin had no immediate effect on cognitive performance.61
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.
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).62 Clinical trials of these antioxidants are needed to confirm the possible benefits suggested by this study.
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
1. Craik FIM, Salthouse TA. Handbook of Aging and Cognition. Hillsdale, NJ: Erlbaum, 1992.
2. Smith GE, Petersen RC, Parisi JE, et al. Definition, course, and outcome of mild cognitive impairment. Aging Neuropsychol Cogn 1996;3:141–7.
3. Brayne C, Gill C, Paykel ES, et al. Cognitive decline in an elderly population—a two wave study of change. Psychological Study of Medicine 1995;25:673–83.
4. Youngjohn JR, Larrabee GJ, Crook TH. Discriminating age-associated memory impairment and Alzheimer’s disease. Psychol Assess 1992;4:54–9.
5. Hänninen T. Age-associated memory impairment: A neuropsychological and epidemiological study. Neurologian klinikan julkaisusarja 1996;39 [abstract].
6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994, 684.
7. Levy R. Aging-associated cognitive decline. Int Psychogeriatr 1994;6:63–8 [review].
8. Rubin EH, Storandt M, Miller JP, et al. A prospective study of cognitive function and onset of dementia in cognitively healthy elders. Arch Neurol 1998;55(3):395–401.
9. Bolla KI, Lindgren KN, Bonaccorsy C, Bleecker ML. Memory complaints in older adults: Fact or fiction? Arch Neurol 1991;48:61–4.
10. Lezak M. Neuropsychological Assessment, 3rd ed. New York: Oxford, 1995.
11. Spreen O, Strauss E. A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary. New York: Oxford, 1991.
12. La Rue A. Aging and Neuropsychological Assessment. New York: Plenum, 1992.
13. Nussbaum, PD, ed. Handbook of Neuropsychology and Aging. New York: Plenum, 1997.
14. Ferris SH, Kluger A. Commentary on age-associated memory impairment, age-related cognitive decline and mild cognitive impairment. Aging Neuropsychol Cogn 1996;3:148–53.
15. Rediess S, Caine ED. Aging, cognition, and DSM-IV. Aging Neuropsychol Cogn 1996;3:105–17.
16. Solfrizzi V, Panza F, Torres F, et al. High monounsaturated fatty acids intake protects against age-related cognitive decline. Neurology 1999;52(8):1563–9.
17. Jarvis MJ. Does caffeine enhance absolute levels of cognitive performance? Psychopharmacology (Berl) 1993;110(1–2):45–52.
18. Joseph JA, Shukitt-Hale B, Denisova NA, et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci 1998;18(19):8047–55.
19. Perrig WJ, Perrig P, Stahelin HB. The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc 1997;45(6):718–24.
20. White LR, Petrovitch H, Ross GW, et al. Brain aging and midlife tofu consumption. J Am Coll Nutr 2000;19:242–55.
21. Di Carlo A, Baldereschi M, Maggi S, et al. Prevalence and risk factors of age-related cognitive decline: The Italian longitudinal study on aging (ILSA). American Academy of Neurology, 50th Annual Meeting [abstract] P04.103.
22. Kilander L, Nyman H, Boberg M, et al. Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. Hypertension 1998;31(3):780–6.
23. Williams P, Lord SR. Effects of group exercise on cognitive functioning and mood in older women. Aust N Z J Public Health 1997;21(1):45–52.
24. Emery CF, Huppert FA, Schein RL. Relationships among age, exercise, health, and cognitive function in a British sample. Gerontologist 1995;35(3):378–85.
25. West RL, Crook TH. Video training of imagery for mature adults. Appl Cogn Psychol 1991;6: 307–20.
26. Caprio-Prevette MD, Fry PS. Memory enhancement program for community-based older adults: development and evaluation. Exp Aging Res 1996;22(3):281–303 [review].
27. Abraham IL, Neundorfer MM, Currie LJ. Effects of group interventions on cognition and depression in nursing home residents. Nurs Res 1992;41(4):196–202.
28. Cipolli C, Chiari G. [Effects of L-acetylcarnitine on mental deterioration in the aged: initial results.] Clin Ter 1990;132(6 Suppl):479–510 [in Italian].
29. Salvioli G, Neri M. L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res 1994;20(4):169–76.
30. Genazzani E. [A controlled clinical study on the efficacy of L-acetylcarnitine in the treatment of mild to moderate mental deterioration in the aged. Conclusions.] Clin Ter 1990;132(6 Suppl):511–2.
31. Garzya G, Corallo D, Fiore A, et al. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res 1990;16(2):101–6.
32. Bonavita E. Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol 1986;24(9):511–6.
33. Passeri M, Iannuccelli M, Ciotti G, et al. Mental impairment in aging: selection of patients, methods of evaluation and therapeutic possibilities of acetyl-L-carnitine. Int J Clin Pharmacol Res 1988;8(5):367–76.
34. Maggioni M, Picotti GB, Bondiolotti GP, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand 1990;81(3):265–70.
35. 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(2):123–33.
36. Sakai M, Yamatoya H, Kudo S. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J Nutr Sci Vitaminol (Tokyo) 1996;42:47–54.
37. Kidd PM. Don’t believe everything you read. . .a sequel. Point. Townsend Letter for Doctors Patients 1997;July:122–4 [editorial].
38. Gaby AR. Don’t believe everything you read. CounterPoint. Townsend Letter for Doctors Patients 1997;July:125–6 [editorial].
39. Furushiro M, Suzuki S, Shishido Y, et al. Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice. Jpn J Pharmacol 1997;75:447–50.
40. Sakai M, Yamatoya H, Kudo S. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J Nutr Sci Vitaminol (Tokyo) 1996;42:47–54.
41. Blokland A, Honig W, Brouns F, et al. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS. Nutrition 1999;15:778–83.
42. Gindin J, Novikov M, Kedar D, et al. The effect of plant phosphatidylserine on age-associated memory impairment and mood in the functioning elderly. Rehovot, Israel: Geriatric Institute for Education and Research, and Department of Geriatrics, Kaplan Hospital, 1995.
43. Jorissen BL, Brouns F, Van Boxtel MPJ, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr Neurosci 2001;4:121–34.
44. Durga J, van Boxtel MPJ, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208–16.
45. 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.
46. 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;35:425–30.
47. 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;3:201–9.
48. 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.
49. Thal LJ, Salmon DP, Lasker B, et al. The safety and lack of efficacy of vinpocetine in Alzheimer's disease. J Am Geriatr Soc 1989;37:515–20.
50. Fischhof PK, Moslinger-Gehmayr R, Herrmann WM, et al. Therapeutic efficacy of vincamine in dementia. Neuropsychobiology 1996;34:29–35.
51. Madigan SM, Tracey F, McNulty H, et al. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people. Am J Clin Nutr 1998;68(2):389–95.
52. Tolonen M, Schrijver J, Westermarck T, et al. Vitamin B6 status of Finnish elderly. Comparison with Dutch younger adults and elderly. The effect of supplementation. Int J Vitam Res 1988;58(1):73–7.
53. Deijen JB, van der Beek EJ, Orlebeke JF, et al. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology (Berl) 1992;109(4):489–96.
54. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992;40(2):168–72.
55. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720–8.
56. Myers BL, Badia P. Changes in circadian rhythms and sleep quality with aging: mechanisms and interventions. Neurosci Biobehav Rev 1995;19(4):553–71. Published erratum appears in Neurosci Biobehav Rev 1996;20(2):I–IV.
57. Dollins AB, Zhdanova IV, Wurtman RJ, et al. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A 1994;91(5):1824–8.
58. Dori D, Casale G, Solerte SB, et al. Chrono-neuroendocrinological aspects of physiological aging and senile dementia. Chronobiologia 1994;21(1–2):121–6.
59. Comperatore CA, Lieberman HR, Kirby AW, et al. Melatonin efficacy in aviation missions requiring rapid deployment and night operations. Aviat Space Environ Med 1996;67(6):520–4.
60. Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 1998;25(3):177–83.
61. Slotten HA, Krekling S. Does melatonin have an effect on cognitive performance? Psychoneuro-endocrinology 1996;21(8):673–80.
62. Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000;54:1265–72.
63. Allain H, Raoul P, Lieury A, et al. Effects of two doses of ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects. Clin Ther 1993;15(3):549–58.
64. Rai GS, Shovlin C, Wesnes KA. A double-blind, placebo-controlled study of Ginkgo biloba extract (‘tanakan’) in elderly patients with mild to moderate memory impairment. Curr Med Res Opin 1991;12(6):350–5.
65. Brautigam MRH, Blommaert FA, Verleye G, et al. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double-blind placebo-controlled study. Phytomedicine 1998;5:425–34.
66. Wesnes K, Simmons D, Rook M. A double-blind, placebo-controlled trial of Tanakan in the treatment of idiopathic impairment in the elderly. Human Psychopharmacol 1987;2:159–69.
67. Israel L, Dell’Accio E, Martin G, Hugonot R. Ginkgo biloba extract and memory training programs—comparative assessment on elderly outpatients. Psychologie Médicale 1987;19:1431–9.
68. Gräbel E. The influence of Ginkgo biloba extract (EGb 761) on mental performance: A double-blind study under computerized measurement conditions in patients with cerebral insufficiency. Fortschr Med 1992;110:73–6.
69. Winther K, Randlov C, Rein E, Mehlsen J. Effects of Ginkgo biloba extract on cognitive function and blood pressure in elderly subjects. Curr Ther Res 1998;59:881–8.
70. Van Dongen M, van Rossum E, Kessels AGH, 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;48:1183–94.
71. Wang Z, Ren G, Zhao Y, et al. A double-blind study of huperzine A and piracetam in patients with age-associated memory impairment and dementia. In: Kanba S, Richelson E, eds. Herbal Medicines for Nonpsychiatric Diseases. Tokyo: Seiwa Shoten Publishers, 1999, 39–50.
72. Singh HK, Dhawan BN. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. (Brahmi). Indian J Pharmacol 1997;29:S359–S365.
73. Singh HK, Rastogi RP, Srimal RC, Dhawan BN. Effect of bacosides A and B on avoidance responses in rats. Phytother Res 1988;2:70–5.
74. Singh HK, Dhawan BN. Effect of Bacopa monniera Linn. (brahmi) extract on avoidance responses in rat. J Ethnopharmacol 1982;5:205–14.
75. Sharma R, Chaturvedi C, Tewari PV. Efficacy of Bacopa monniera in revitalizing intellectual functions in children. J Res Edu Ind Med 1987:1:12.
76. Roodenrys S, Booth D, Bulzomi S, et al. Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27:279–81.
77. Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001;156:481–4.
78. Nathan PJ, Clarke J, Lloyd J, et al. The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects. Hum Psychopharmacol 2001;16:345–51.