Review Article

Complementary and Integrative Approaches to Dementia

Authors: Víctor S. Sierpina, MD, Michelle Sierpina, MS, Jose A. Loera, MD, Loretta Grumbles, MD

Abstract

This is a review that evaluates complementary and alternative approaches to dementia and places them into an integrative framework. While many therapies in popular use have yet to be supported by “best-evidence” trials or meta-analysis, conventional treatments for dementia are clearly suboptimal. This encourages both health care providers and patients' families to expand their search for options for this difficult condition. We provide an in-depth review of mind-body and biologic therapies that have been studied or are in use for Alzheimer disease to provide a context for the busy clinician along with levels of evidence supporting them. Several principles emerge: the need for holism of care, support for care providers, the importance of social engagement and behavioral interventions, and the limited role of medication, nutriceuticals, and botanicals. Without dramatic and well-proven therapies, we find there is hope for the future in clinical care and research advances based on a number of promising therapies we describe.

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References

1. Hamdy R. Featured CME topic: dementia. Fact sheets. South Med J 2001;94:673–677.
 
2. Pryse-Phillips W. Do we have drugs for dementia? No. Arch of Neurology 1999;56:735–737.
 
3. Hensley S. New hope seen for vaccine for Alzheimer's. Wall Street Journal July 22, 2004:B1–B2.
 
4. Sierpina V, Wollschlaeger B, Blumenthal M. Ginkgo biloba. Am Fam Physician 2003;68:923–926.
 
5. Joseph J, Denisova N, Arendash G, et al. Bluebery supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci 2003;6:153–162.
 
6. Khalsa D. The Cortisol Connection, Healthy Aging, in: Brain Longevity. New York, Warner Books, 1997, pp 3–23.
 
7. Null G. Ultimate Anti-Aging Program. New York, Broadway Books, 1999.
 
8. Whitehouse P. The end of Alzheimer disease. Alzheimer Dis Assoc Disord 2001;15:59–62.
 
9. Astin J, Shapiro S, Eisenberg D, et al. Mind-body medicine: state of the science, implications for practice. J Am Bd Fam Prac 2003;16:131–147.
 
10. Fischer P, Laschinger H. A relaxation training program to increase self-efficacy for anxiety control in Alzheimer family caregivers. Holistic Nurs Prac 2001;15:47–58.
 
11. Rowe M, Alfred D. The effectiveness of slow stroke massage in diffusing agitated behavior in individuals with Alzheimer's disease. J Ger Nurs 1999;25:22–34.
 
12. Cohen-Mansfield J. Nonpharmacological interventions for inappropriate behaviors in dementia. Am J Psychiatr 2001;9:261–381.
 
13. Kim E, Buschmann M. The effect of expressive physical touch. Int J Nurs Studies 1999;36:235–243.
 
14. Woods D, Dimond M. The effect of therapeutic touch on agitated behavior and cortisol in persons with Alzheimer's disease. Biol Res Nursing 2002;4:104–114.
 
15. Kircher T, Teutsch E, Wormstall H, et al. Effects of autogenic training in elderly patients [article in German]. Z Gerontol Geriatr 2002;35:157–165.
 
16. Oken B. Complementary Therapies in Neurology: An Evidence-based Approach. New York, Parthenon Publishing, 2004.
 
17. Simon E, Canonico M. Use of hypnosis in controlling lumbar puncture distress in an adult needle-phoic dementia patient. Int J Clin Exp Hypn 2001;49:56–67.
 
18. Adams L, Gatchel R, Gentry C. CAM for cognitive functioning in the elderly. ATHM 2001;7:52–61.
 
19. Lubar J. Neocortical dynamics: implications for understanding the role of neurofeedback and related techniques for the enhancement of attention. Appl Psychophysiol Biofeedback 1997;22:111–126.
 
20. Hanley I, Mcguire R, Boyd W. Reality orientation and dementia: a controlled trial of two approaches.Br J Psychiatr 1981;138:10–14.
 
21. Mace N. The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer's Disease, Related Dementing Illnesses, and Memory Loss in Later Life. Baltimore, Johns Hopkins University Press, 1999, ed 3.
 
22. Teri L, Gibbons LE, McCurry SM, et al. Exercise plus behavior management in patients with Alzheimer's disease: a randomized controlled trial. JAMA 2003;290:2015–2022.
 
23. Heliker D. Transformation of story to practice: an innovative approach to long-term care. Issues in Mental Health Nursing 1999;20:513–525.
 
24. Heliker D, Brophy E, Naughton-Walsh M, et al. A study of professional health care students attitudes toward the elderly. J Nurs Educ 1993;32:370–373.
 
25. Connell C, Shaw B, Holmes S, et al. The development of an Alzheimer's disease channel for the Michigan Interactive Health Kiosk Project. Health Communication 2003;8:11–22.
 
26. Briones D, Ramirez A, Guerrero M, et al. Determining cultural and psychosocial factors in Alzheimer's disease among Hispanic populations. Alzheimer Dis Assoc Disord 2002;16(suppl 2):S86–S88.
 
27. Davis R, Massman P, Doody R. Cognitive intervention in Alzheimer disease: a randomized placebo controlled study. Alzheimer Dis Assoc Disord 2001;15:1–9.
 
28. Monsch A, Ermini-Funfschilling D, Mulligan R, et al. Memory clinics in Switzerland. Collaborative group of Swiss Memory Clinics. Ann Med Interne 1998;149:221–222.
 
29. Gurka P, Marksteiner J. Psychosocial therapy of patients with dementia [article in German]. Wien Med Wochenschr 2002;152102–106.
 
30. Teri L. Behavior treatment of depression in patients with dementia. Alzheimer's Disease Assoc Disord 1994;8(suppl 3):66–74.
 
31. Merrick J, Cahana C, Lotan M, et al. Snoezelen or controlled multisensory stimulation. Treatment aspects from Israel. Scientific World Journal 2004;4:307–314.
 
32. The Alzheimer's Information Site. Available at: http://www.alzinfo.org/news/1_5_04.aspx. Accessed October 21, 2004.
 
33. Fitzsimmons S, Buettner L. Health promotion for the mind, body, and spirit: a college course for older adults with dementia. Am J Alzheimers Dis Other Demen 2003;18:282–290.
 
34. Snyder M, Tseng Y, Brandt C, et. al. Challenges of implementing intervention research in persons with dementia: example of a glider swing intervention. Am J Alzheimers Dis Other Demen 2001;16:51–56.
 
35. Basting A. TimeSlips© Educational Guide. Milwaukee, University of Wisconsin Press, 2002.
 
36. Basting A. It's 1924 and Somewhere in Texas, Two Nuns Are Driving a Backwards Volkswagen: Storytelling with People with Dementia, in McFadden SH, Atchley RC (eds): Aging and the Meaning of Time. New York, Springer, 2001, pp 131–149.
 
37. Brotons M, Marti P. Music therapy with Alzheimer's patients and their family caregivers: a pilot project. Journal of Music Therapy 2003;40:138–150.
 
38. Clark ME, Lipe AW, Bilbrey M. Use of music to decrease aggressive behaviors in people with dementia. Journal of Gerontological Nursing 1998;24:7–10.
 
39. Lustbader J, Cirilli M, Lin C, et al. ABAD directly linked AB to mitochondrial toxicity in Alzheimer's Disease. Science 2004;304:448–452.
 
40. Masterson D. Cholinesterase inhibitors in the treatment of Alzheimer's disease and related dementias. Clin Geriatr Med 2004;20:59–68.
 
41. Budavari S. The Merck Index. Whitehouse Station, Merck & Co., 1996, ed 12.
 
42. Liu J, Zhu Y, Yu C, et al. The Structure of huperzine A and B, two new alkaloids exhibiting marked anticoholinesterase activity. Can J Chem 1986;64:837–839.
 
43. Skolnick AA. Old chinese herbal medicine used for fever yields possible new Alzheimer disease therapy. JAMA 1997;277:776.
 
44. Xu S, Gao Z, Weng Z, et al. Efficacy of tablet huperzine: a memory, congnition and behavior in Alzheimer's disease. Zhongguo Yao Li Xue Bao 1995;16:391–395.
 
45. Xu S, Cai Z, Qu Z, et al. Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Zhongguo Yao Li Xue Bao 1999;20:486–490.
 
46. Zhang R, Tang X, Han Y, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. Zhongguo Yao Li Xue Bao 1991;12:250–252.
 
47. Wang X, Zhang J, Yang H, et al. Modulation of NMDA receptor by huperzine A in rat cerebral cortex.Zhongguo Yao Li Xue Bao 1999;20:31–35.
 
48. Natural Medicines Comprehensive Database. Available at:http://www.naturaldatabase.com/(ydk2ga55h3zyw055dglukn55)/home.aspx?li=1&st=2&cs=&s=ND. Accessed October 21, 2004.
 
49. Pepping J. Huperzine A. Review. American Journal of Health System Pharmacy 2000;57:530,533–534.
 
50. Mayeux R, Sano M. Treatment of Alzheimer's disease. N Engl J Med 1999;341:1670–1679.
 
51. Ott B, Owens N. Complementary and alternative medicines for Alzheimer's disease. J Geriatr Psyciatry Neurol 1998;11:163–173.
 
52. Sano M, Ernest D, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer disease. The Alzheimer’s Disease Cooperative Study. NEJM 1997;336:1216–1222.
 
53. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimers dementia. Curr Med Res Opin 1990;11:638–647.
 
54. Pettegrew J, Klunk W, Panchalingam K, et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995;16:1–4.
 
55. Thal L, Carta A, Clarke W, et al. 1-year muticenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology 1996;47:705–711.
 
56. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology 1991;41:1726–1732.
 
57. Brooks Jr., Yesavage J, Carta A, et al. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study of the trilinear approach.Int Psychogeriatr 1998;10:193–203.
 
58. Montgomery S, Thal L, Amrein R. Meta-analysis of double blind randomized controlled clinical trials acetyl-L-carnitine versus placebo in treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 2003;18:61–71.
 
59. Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev2003;2:CD003158.
 
60. Tan J, Bluml S, Hoang T, et al. Lack of effect of Oral choline supplement on the concentrations of choline metabolites in human brain. Magn Reson Med 1998;39:1005–1010.
 
61. Mohs R, Davis K, Tinklenberg J, et al. Choline chloride effects on memory in the elderly. Neurobiol Aging 1980;1:21–25.
 
62. Brinkman S, Smith R, Meyer J, et al. Lecithin and memory training in suspected Alzheimer's disease. J Gerontol 1982;37:4–9.
 
63. Pomara N, Domino E, Yoon H, et al. Failure of single-dose lecithin to alter aspects of central choliner activity in Alzheimer's disease. J Clin Psychiatry 1983;44:293–295.
 
64. Etienne P, Dastoor D, Gauthier S, et al. Alzheimer disease: lack of effect of lecithin treatment for 3 months. Neurology 1981;31:1552–1554.
 
65. Heiss W, Kessler J, Mielke R, et al. Long-term effects of phosphatidyslerine, pyritinol and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Dementia1994;5:88–98.
 
66. Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer's disease.Psychopharmacol Bull 1992;28:61–66.
 
67. Delwaide P, Gyselynck-Mambourg A, Hurlet A, et al. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand 1986;73:136–140.
 
68. Funfgeld E, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidyslerine (PS) in Parkinsonian patients with senile dementia of Alzheimer's types (SDAT). Prog Clin Biol Res1989;317:1235–1246.
 
69. Mecocci P, Polidori M, Cherubini A, et al. J. Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer's Disease. Arch Neurol 2002;59:794–798.
 
70. Ishizuka K, Kimura T, Yoshitake J, et al. Possible assessment for antioxidant capacity in Alzheimer's disease by measuring lymphocyte heme-oxygenase-1 expression with real-time RT-PCR.Ann NY Acad Sci 2002;977:173–178.
 
71. Rinaldi P, Polidori M, Metastasio A, et al. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiology of Aging 2003;24:915–919.
 
72. Selley M, Close D, Stern S. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiology of Aging 2002;23:383–388.
 
73. Morris M, Evans D, Bienias J, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer's disease in a biracial community study. JAMA 2002;287:3230–3237.
 
74. Luchsinger J, Tang M, Shea S, et al. Antioxidant vitamin intake and risk of Alzheimer's disease.Arch Neurol 2003;60:203–208.
 
75. Williamson K, Gabbita S, Mou S, et al. The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer's brain. Nitric Oxide: Biology and Chemistry 2002;6:221–227.
 
76. Weyer G, Babej-Dolle R, Hadler D, et al. A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. Neuropsychobiology 1997;36:73–82.
 
77. Gutzmann H, Hadler D. Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2-year double-blind multicentre study. J Neural Transm Suppl 1998;54:301–310.
 
78. Chandra R. Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects. Nutrition 2001;17:709–712.
 
79. Stewart WF, Kawas C, Corrada M, et al. Risk of Alzheimer's disease and duration of NSAID use [see comment]. Neurology 1997;48:626–632.
 
80. Luo Y, Smith J, Burdick A, et al. Inhibition of amyloid-beta aggregation and caspase-3 activation by the gingko biloba extract EGb 761. Proc Natl Acad Sci USA 2004;99:12197–12202.
 
81. Le Bars P. Magnitude of effect and special approach to gingko biloba extract EGb 761 in cognitive disorders. Pharmacopsychiatry 2003;36(suppl 1):S44–49.
 
82. Ahlemeyer B, Krieglstein J. Pharmacological studies supporting the therapeutic use of ginkgo biloba extract for Alzheimer's disease. Pharmacopsychiatry. 2003;36(suppl 1):S8–14.
 
83. Kanowski S, Hoerr R. Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry2003;36:297–303.
 
84. 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.
 
85. Hoskin E, Tang M, Manly J, et al. Elevated sex-hormone binding globulin in elderly women with Alzheimer's disease. Neurobiology of Aging 2004;25:141–147.
 
86. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial [see comment]. JAMA 2003;289:2651–2662.
 
87. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study [see comment]. JAMA 2004;291:2947–2958.
 
88. Kroboth P, Salek F, Pittenger A, Fabian T, Frye R. DHEA and DHEA-S: a review. J Clin Pharmacol1999;39:327–348.
 
89. Sunderland T, Merril C, Harrington M, et al. Reduced plasma dehydroepiandrosterone concentrations in Alzheimer's disease. Lancet 1989;2(8662):570.
 
90. Nasman B, Olsson T, Backstrom T, et al. Viitanene M Serum dehydroepiandrosterone sulfate in Alzheimer's disease and multi-infarct dementia. Biol Psychiatry 1991;30:684–690.
 
91. Wolkowitz O, Kramer J, Reus V, et al. DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study [see comment]. Neurology 2003;60:1071–1076.
 
92. Kuritzky L. DHEA: science or wishful thinking? Hosp Pract (OffEd) 1998;33(5):85–86,92.
 
93. Stoll B. Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk. Eur J Clin Nutr 1999;53:771–775.
 
94. Morales A, Haubrich R, Hwang J, et al. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulationg sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf) 1998;49:421–432.
 
95. Pepeu G, Spignoli G. Nootropic drugs and brain cholinergic mechanics, Prog.Neuropsychopharmaol Biol Psychiatry 1989;1(supp 1):S77–88.
 
96. McDaniel M, Maier S, Einstein G. Brain-specific nutrients: a memory cure? Nutrition 2003;19:957–975.
 
97. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. NEJM 2002;346:476–483.
 
98. Mattson MP. Will caloric restriction and folate protect against AD and PD? Neurology 2003;60:690–695.
 
99. Miller J, Green R, Mungas D, et al. Homocysteine, vitamin B6, and vascular disease in AD patients.Neurology 2002;58:1471–1475.
 
100. Zetterberg H, Nexo E, Regland B, et al. The transcobalamin (TC) codon 259 genetic polymorphism influences holo-TC concentration in cerebrospinal fluid from patients with Alzheimer's disease. Clinical Chemistry 2003;49:1195–1198.
 
101. Nilsson K, Gustafson L, Faldt R, et al. Hyperhomocysteinaemia—a common finding in a psychogeriatric population. Eur J Clin Invest 1996;26:853–859.
 
102. Wang H, Wahlin A, Basun H, et al. Vitamin B12 and folate in relation to the development of Alzheimer's disease. Neurology 2001;56:1188–1194.
 
103. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Intl J Geriatr Psychiatry 2001;16:609–614.
 
104. Clarke R, Smith A, Jobst K, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer's disease. Arch Neurol 1998;55:1449–1455.
 
105. Diaz-Arrastia R. Hyperhomocysteinemia: a new risk factor for Alzheimer's disease? Arch Neurol1988;55:1407–1408.
 
106. Gibson GE, Sheu KF, Blass JP, et al. Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease. Archives of Neruology 1988;45:836–840.
 
107. Eder L, Hirt L, Dunant Y. Possible involvement of thiamine in acetylcholine release. Nature1976;264:186–188.
 
108. Eder L, Dunant Y. Thiamine and cholinergic transmission in the electric organ of Torpedo. I. Cellular localization and functional changes of thiamine and thiamine phosphate esters. Journal of Neurochemistry 1980;35:1278–1286.
 
109. Nolan K, Black R, Sheu K, et al. A trial of thiamine in Alzheimer's disease. Archives of Neurology1991;48:81–83.