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LE Magazine April 2005

Preventing Age-Related Cognitive Decline

By Laurie Barclay, MD

Ginkgo, Ginger, and Aspirin Improve Brain Circulation

Extract of ginkgo biloba, derived from the oldest living species of tree on Earth, is a potent antioxidant53 that helps to counteract age-related changes in blood flow to the brain.54 By dilating and toning blood vessels, interfering with platelet activity to decrease blood clotting, and preventing oxidative damage to mitochondria and nerve cells,54 ginkgo enhances brain activity and energy metabolism,55 and decreases symptoms of depression and memory impairment.56

Ginkgo may be helpful in mild to moderately severe cognitive impairment associated with early Alzheimer’s disease or vascular dementia, according to a study of 202 patients reported in the Journal of the American Medical Association. During one year of treatment, patients receiving ginkgo maintained cognitive function and improved slightly in social functioning, while the placebo group deteriorated in both areas.57

In a review of 40 clinical studies using ginkgo for cerebral vascular insufficiency and for age-related dementia, nearly all trials showed improvements relative to placebo in memory impairment, confusion, fatigue, anxiety, and other symptoms.58 Another review also showed promising benefits in cognitive symptoms without serious side effects in some studies, suggesting the need for a larger, well-designed trial.59

Based on European studies, Germany has approved ginkgo biloba extract for treatment of Alzheimer’s disease and other dementias. In a placebo-controlled study,20 outpatients with mild to moderate Alzheimer’s had significant improvement in attention and memory performance after three months of treatment.60

One study showed no difference in memory scores or perceptions of improvement in cognitive function in healthy adults after six weeks of supplementing with ginkgo,61 whereas another study showed improvements with similar doses.62 A placebo-controlled study in 60 healthy volunteers showed significant improvements after 30 days of ginkgo treatment in speed of information processing, working memory, and executive processing.63 Ginkgo may be most beneficial for short-term memory in healthy adults if given as a single dose of 120 mg rather than as 40 mg three times daily.64

A German study investigated how combining ginkgo and ginger affects learning, memory, and brain oxidative stress in aged rats.65 Like ginkgo, ginger has traditionally been used by herbalists as a circulatory tonic. The investigators found that the ginkgo and ginger combination significantly reduced two indicators of oxidative stress in the brains of aged rats. Additionally, the ginkgo and ginger supplement helped to facilitate spatial learning in the animals.

Low-dose acetylsalicylic acid, or aspirin, acts as a mild blood thinner and lowers the risk of vascular events in humans. Increasing evidence suggests aspirin may also reduce the rate of cognitive decline in the elderly.66 A large study of aspirin’s ability to prevent vascular dementia in the elderly is currently underway in Australia.

Other Nutrients Show Promise

In a mouse model of brain aging, green tea extract prevented both impairments in working memory and shrinking and oxidative DNA damage to brain regions involved in memory.67 An animal model of vascular injury to the brain showed a neuroprotective effect of antioxidants that included rutin, selenium, and garlic oil.68 Aged garlic extract contains phytochemicals that prevent oxidative damage, and has shown the ability to increase cognitive function, memory, and longevity in mouse models of aging.69

Chromium improves control of blood sugar. By increasing insulin-receptor activity within the hypothalamus, a vital center for brain control, it may rejuvenate the aging brain.70 In animal studies, chromium supplements increase activity of nerve chemicals involved in controlling moods, suggesting a possible antidepressant effect.71

Bioflavonoids are a diverse group of plant-derived compounds that exert myriad effects in the body. Quercetin, a bioflavonoid with strong antioxidant properties, is found in a variety of fruits and vegetables. In a study involving mice, quercetin significantly reversed age-related cognitive decline.72 Additionally, quercetin reversed increased markers of oxidative stress and the decline of the crucial antioxidant glutathione in the forebrain, two other age-associated changes.

North American ginseng contains numerous bioactive compounds that exert many beneficial effects. One of the ginsenoside compounds from North American ginseng has been found to prevent memory deficits in rats.73 This compound facilitates the release of the neurotransmitter acetylcholine from the hippocampus, an area of the brain involved in memory and mood.

Conclusion

As science advances our understanding of brain aging, we have discovered many promising paths to preserving cognition well into chronological old age. Lessons learned from animal studies suggest how nutrients may best be combined to prevent age-related cognitive decline.

Free radicals are a significant culprit, interfering with energy metabolism, blood flow, and nerve structure and function. Mitochondrial energy boosters, vitamins, hormones, and other antioxidants are effective weapons in the war against oxidative stress, safely enhancing energy production and blood flow, suppressing inflammation, maintaining the structural integrity of nerve cell components, and facilitating neuronal activity.

Because these antioxidants are involved in vital functions in virtually all organ systems, supplementation to prevent age-related cognitive decline may also help protect against other age-related conditions. Nutrients have different mechanisms of action, so combining them may increase their benefits beyond that expected when each is used individually. Some physicians can offer specific advice about potential interactions of these supplements with prescription medications such as Coumadin®.

Thanks to this nutritional armamentarium, there is reason to hope that age-related cognitive decline need not be an inevitable consequence of aging. With further research, application of these strategies to early Alzheimer’s and other dementias might ultimately help reduce the toll of these dreaded and increasingly common diseases.

Table 1. Formulation of a Dietary Supplement Designed to Reduce
Oxidative Stress and Inflammation, Maintain Membrane and
Mitochondrial Integrity, and Enhance Insulin Sensitivity (mouse doses).

Vitamin B1	0.72 mg/day	Flaxseed oil	21.6 mg/day
Vitamin B3	0.72 mg/day	Folic Acid	0.01 mg/day
Vitamin B	60.72 mg/day	Garlic	21.6 mcg/day
Vitamin B12	0.72 mcg/day	Ginger	7.2 mg/day
Vitamin C	3.6 mg/day	Ginkgo Biloba	1.44 mg/day
Vitamin D	2.5 IU/day	Ginseng (North American)	8.64 mg/day
Vitamin E	1.44 IU/day	Green Tea Extracts	7.2 mg/day
Acetyl-L-Carnitine	14.4 mg/day	L-Glutathione	0.36 mg/day
Lipoic Acid	0.72 mg/day	Magnesium	0.72 mg/day
Aspirin	2.5 mg/day	Melatonin	0.01 mg/day
Beta-Carotene	50.0 IU/day	N-Acetylcysteine	7.2 mg/day
Bioflavonoids	4.32 mg/day	Potassium	0.36 mg/day
Chromium Picolinate	1.44 mcg/day	Rutin	0.72 mg/day
Cod Liver Oil	5.04 IU/day	Selenium	1.08 mcg/day
Coenzyme Q10	0.44 mg/day	Zinc (chelated)	0.14 mg/day
DHEA	0.15 mg/day
Source: Lemon JA, Boreham DR, Rollo CD. A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes. Exp Biol Med (Maywood). 2003 Jul;228(7):800-10.

References

1. Lemon JA, Boreham DR, Rollo CD. A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes. Exp Biol Med (Maywood.). 2003 Jul;228(7):800-10.

2. Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or R-alpha-lipoic acid. Proc Natl Acad Sci USA. 2002 Feb 19;99(4):1876-81.

3. Hagen TM, Liu J, Lykkesfeldt J, et al. Feed- ing acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA. 2002 Feb 19;99(4):1870-5.

4. Aureli T, Di Cocco ME, Capuani G, et al. Effect of long-term feeding with acetyl-L-carnitine on the age-related changes in rat brain lipid composition: a study by 31P NMR spectroscopy. Neurochem Res. 2000 Mar;25(3):395-9.

5. Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mito-chondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha-lipoic acid. Proc Natl Acad Sci USA. 2002 Feb 19;99(4):2356-61.

6. Available at: www.berkeley.edu/news/media/releases/2002/02/19_diet.html. Accessed January 14, 2005.

7. McDaniel MA, Maier SF, Einstein GO. “Brain-specific” nutrients: a memory cure? Nutrition. 2003 Nov;19(11-12):957-75.

8. Brooks JO, III, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer’s disease: a reanalysis of a double-blind, placebo-con- trolled study using the trilinear approach. Int Psychogeriatr. 1998 Jun;10(2):193-203.

9. Bliznakov G, Hunt GL. The Miracle Nutrient: Coenzyme Q10. New York: Bantam Books; 1988.

10. Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentra- tions and exerts neuroprotective effects. Proc Natl Acad Sci USA. 1998 Jul 21;95(15):8892-7.

11. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the function- al decline. Arch Neurol. 2002 Oct;59(10):1541-50.

12. Gamoh S, Hashimoto M, Hossain S, Masumura S. Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. Clin Exp Pharmacol Physiol. 2001 Apr;28(4):266-70.

13. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004 Nov;6(6):461-7.

14. Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord. 1998 Mar;48(2-3):149-55.

15. Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998 Mar 1;43(5):315-9.

16. Maes M, Christophe A, Delanghe J, et al. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res. 1999 Mar 22;85(3):275-91.

17. Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6.

18. Suzuki M, Wright LS, Marwah P, Lardy HA, Svendsen CN. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. Proc Natl Acad Sci USA. 2004 Mar 2;101(9):3202-7.

19. Kahonen MH, Tilvis RS, Jolkkonen J, Pitkala K, Harkonen M. Predictors and clin- ical significance of declining plasma dehydroepiandrosterone sulfate in old age. Aging (Milano.). 2000 Aug;12(4):308-14.

20. Racchi M, Balduzzi C, Corsini E. Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the “fountain of youth”. CNS Drug Rev. 2003;9(1):21-40.

21. Rhodes ME, Li PK, Flood JF, Johnson DA. Enhancement of hippocampal acetylcholine release by the neurosteroid dehydroepiandrosterone sulfate: an in vivo microdialysis study. Brain Res. 1996 Sep 16;733(2):284-6.

22. Maurice T, Junien JL, Privat A. Dehy- droepiandrosterone sulfate attenuates dizocilpine-induced learning impairment in mice via sigma 1-receptors. Behav Brain Res. 1997 Feb;83(1-2):159-64.

23. Murialdo G, Nobili F, Rollero A, et al. Hip- pocampal perfusion and pituitary-adrenal axis in Alzheimer’s disease. Neuropsychobiology. 2000;42(2):51-7.

24. Danenberg HD, Haring R, Fisher A, et al. Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer’s amyloid precursor protein. Life Sci. 1996;59(19):1651-7.

25. Swierczynski J, Kochan Z, Mayer D. Dietary alpha-tocopherol prevents dehydroepiandrosterone-induced lipid peroxidation in rat liver microsomes and mitochondria. Toxicol Lett. 1997 Apr 28;91(2):129-36.

26. Metzger C, Mayer D, Hoffmann H, et al. Sequential appearance and ultrastructure of amphophilic cell foci, adenomas, and carcinomas in the liver of male and female rats treated with dehydroepiandrosterone. Toxicol Pathol. 1995 Sep;23(5):591-605.

27. Magri F, Sarra S, Cinchetti W, et al. Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians. J Pineal Res. 2004 May;36(4):256-61.

28. Peck JS, LeGoff DB, Ahmed I, Goebert D. Cognitive effects of exogenous melatonin administration in elderly persons: a pilot study. Am J Geriatr Psychiatry. 2004 Jul;12(4):432-6.

29. Morris MC, Evans DA, Bienias JL, et al. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1093-9.

30. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adeno-sylmethionine) in neurological disorders. Drugs. 1994 Aug;48(2):137-52.

31. McDowell I. Alzheimer’s disease: insights from epidemiology. Aging (Milano.). 2001 Jun;13(3):143-62.

32. La Rue A, Koehler KM, Wayne SJ, et al. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr. 1997 Jan;65(1):20-9.

33. Wang HX, Wahlin A, Basun H, et al. Vita- min B(12) and folate in relation to the development of Alzheimer’s disease. Neurology. 2001 May 8;56(9):1188-94.

34. Hassing L, Wahlin A, Winblad B, Backman L. Further evidence on the effects of vitamin B12 and folate levels on episodic memory functioning: a population-based study of healthy very old adults. Biol Psychiatry. 1999 Jun 1;45(11):1472-80.

35. Carmel R. Subtle cobalamin deficiency. Ann Intern Med. 1996 Feb 1;124(3):338-40.

36. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;(4):CD004514.

37. Calvaresi E, Bryan J. B vitamins, cognition, and aging: a review. J Gerontol B Psychol Sci Soc Sci. 2001 Nov;56(6):327-39.

38. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry. 2001 Jun;16(6):609-14.

39. Deijen JB, van der Beek EJ, Orlebeke JF, van den BH. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology (Berl). 1992;109(4):489-96.

40. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998 Apr;78(2):547-81.

41. Fukui K, Omoi NO, Hayasaka T, et al. Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Ann NY Acad Sci. 2002 Apr;959:275- 84.

42. Miyamoto M, Murphy TH, Schnaar RL, Coyle JT. Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther. 1989