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
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
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An isolated, unpublished double-blind human study used soy-derived PS in an evaluation of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
In a double-blind trial, supplementing with 50 mg of beta-carotene every other day for 18 years appeared to
slow the loss of cognitive function in middle-aged healthy males. Short-term supplementation
(1 year) was not beneficial.44
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.45 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.46 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.47 Other double-blind trials have reported similar effects of vinpocetine
in people with some types of dementia or age-related cognitive decline.48
49 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
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.51 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 65.52 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.53 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
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.55 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.56
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.57 58 59 60 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.61 However, in a double-blind case study of one
healthy person, 1.6 mg of melatonin had no immediate effect on cognitive
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).63 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
4. Youngjohn JR, Larrabee GJ, Crook TH. Discriminating age-associated
memory impairment and Alzheimer’s disease. Psychol Assess
5. Hänninen T. Age-associated memory impairment: A
neuropsychological and epidemiological study. Neurologian klinikan julkaisusarja
6. American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association,
7. Levy R. Aging-associated cognitive decline. Int Psychogeriatr
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
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:
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:
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
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
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
19. Perrig WJ, Perrig P, Stahelin HB. The relation between antioxidants
and memory performance in the old and very old. J Am Geriatr Soc
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
23. Williams P, Lord SR. Effects of group exercise on cognitive
functioning and mood in older women. Aust N Z J Public Health
24. Emery CF, Huppert FA, Schein RL. Relationships among age, exercise,
health, and cognitive function in a British sample. Gerontologist
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
27. Abraham IL, Neundorfer MM, Currie LJ. Effects of group interventions
on cognition and depression in nursing home residents. Nurs Res
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
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
32. Bonavita E. Study of the efficacy and tolerability of
L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol
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
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
44. Grodstein F, Kang JH, Glynn RJ, et al. A randomized trial of beta
carotene supplementation and cognitive function in men: the Physicians' Health Study II.
Arch Intern Med 2007;167:2184–90
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. Fischhof PK, Moslinger-Gehmayr R, Herrmann WM, et al. Therapeutic
efficacy of vincamine in dementia. Neuropsychobiology 1996;34:29–35.
52. 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.
53. 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.
54. 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.
55. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of
cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr
56. 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.
57. 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
58. 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.
59. Dori D, Casale G, Solerte SB, et al. Chrono-neuroendocrinological
aspects of physiological aging and senile dementia. Chronobiologia
60. Comperatore CA, Lieberman HR, Kirby AW, et al. Melatonin efficacy in
aviation missions requiring rapid deployment and night operations. Aviat Space Environ
61. Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep,
mood, and cognition in elderly with mild cognitive impairment. J Pineal Res
62. Slotten HA, Krekling S. Does melatonin have an effect on cognitive
performance? Psychoneuro-endocrinology 1996;21(8):673–80.
63. 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
64. 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
65. 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.
66. 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.
67. Wesnes K, Simmons D, Rook M. A double-blind, placebo-controlled trial
of Tanakan in the treatment of idiopathic impairment in the elderly. Human
68. 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.
69. 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.
70. 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
71. 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.
72. 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.
73. Singh HK, Dhawan BN. Neuropsychopharmacological effects of the
Ayurvedic nootropic Bacopa monniera Linn. (Brahmi). Indian J Pharmacol
74. 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.
75. Singh HK, Dhawan BN. Effect of Bacopa monniera Linn. (brahmi) extract
on avoidance responses in rat. J Ethnopharmacol 1982;5:205–14.
76. Sharma R, Chaturvedi C, Tewari PV. Efficacy of Bacopa monniera in
revitalizing intellectual functions in children. J Res Edu Ind Med 1987:1:12.
77. Roodenrys S, Booth D, Bulzomi S, et al. Chronic effects of Brahmi
(Bacopa monnieri) on human memory. Neuropsychopharmacology. 2002;27:279–81.
78. Calabrese C, Gregory WL, Leo M, et al. Effects of a standardized
Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a
randomized, double-blind, placebo-controlled trial. J Altern Complement Med
79. 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.
80. 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