Patient Care Neurology & Psychiatry - November 2007 - (Page 18)

I Dementia ChEI therapy with rivastigmine, donepezil, or galantamine is recommended as standard first-line therapy in patients with mild to moderate AD.39 Treatment with ChEIs, alone or in combination with memantine as appropriate for the stage of disease, may be considered as a first-line option when nonpharmacologic strategies are deemed insufficient for problem behaviors.40 Future therapies As the mechanisms that cause AD are discovered, therapeutic targets are identified and agents are developed to interrupt these pathogenic mechanisms (see the illustration, page 11). The natural tendency for amyloid beta (Abeta) to aggregate into a 12-molecule oligomer (a dodecamer) at 37ºC (body temperature) has led researchers to demonstrate that these dodecamers (termed ADDLs, for Abeta-derived diffusible ligands) disrupt synaptic plasticity, therefore memory and learning, attach to receptors on cholinergic neurons and disrupt the geometry and cytoskeleton of the neuron, and promote programmed cellular death.41 ADDLs appear to disaggregate when exposed to curcumin, the potent antioxidant found in turmeric. 42 In locations where turmeric is plentiful in diet and in traditional medicine, such as India, the prevalence of AD is markedly lower than it is in the US population. Omega-3 fatty acid appears protective as well, as are statins, pPAR gamma inhibitors, sulindac and ibuprofen, estrogen and selective estrogen receptor modulators, most antioxidants (vitamin C and E in combination), calcium channel blockers, ACE inhibitors, angiotensin receptor blockers used in controlling BP alcohol in moderation, and staying , active mentally. Pharmacologic therapy with currently available agents should ideally be continued until there are no meaningful social interactions and quality of life has irreversibly deteriorated. Kindness and loving care should ideally be continued indefinitely. I Drs Standridge and Talbert disclose that they have no financial relationship with any manufacturer in this area of medicine. 22. Trinh NH, Hoblyn J, Mohanty S, et al. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289(2):210-216. 23. Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med. 2007;357(14):1382-1392. 24. Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology. 2004;63(2):214-219. 25. Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003; 169(6):557-564. 26. Geldmacher DS, Provenzano G, McRae T, et al. Donepezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51(7):937-944. 27. Farlow M, Potkin S, Koumaras B, et al. Analysis of outcome in retrieved dropout patients in a rivastigmine vs placebo, 26-week, Alzheimer disease trial. Arch Neurol. 2003;60(6):843-848. 28. Hashimoto M, Kazui H, Matsumoto K, et al. Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer’s disease? Am J Psychiatry. 2005;162(4):676-682. 29. Arias E, Ales E, Gabilan NH, et al. Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors. Neuropharmacology. 2004;46(1):103-114. 30. Takada Y, Yonezawa A, Kume T, et al. Nicotinic acetylcholine receptormediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons. J Pharmacol Exp Ther. 2003;306(2):772-777. 31. Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330:613-622. 32. Shimizu E, Tang YP, Rampon C, et al. NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science. 2000;290:1170-1174. 33. Danysz W, Parsons CG, Möbius HJ, et al. Neuroprotective and symptomalogical action of memantine relevant for Alzheimer’s disease—a unified glutamatergic hypothesis on the mechanism of action. Neurotoxicity Res. 2000;2:85-97. 34. Tariot PN, Farlow MR, Grossberg GT, et al; for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. JAMA. 2004; 291(3):317-324. 35. Reisberg B, Doody R, Stoffler A, et al; for the Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003;348(14):1333-1341. 36. Winblad B, Poritis N. Memantine in severe dementia: Results of the 9MBest Study. Int J Geriatr Psychiatry. 1999;14:135-146. 37. Winblad B, Kilander L, Eriksson S, et al; Severe Alzheimer’s Disease Study Group. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. Lancet. 2006;367(9516): 1057-1065. 38. Feldman HH, Schmitt FA, Olin JT; Memantine MEM-MD-02 Study Group. Activities of daily living in moderate-to-severe Alzheimer disease: an analysis of the treatment effects of memantine in patients receiving stable donepezil treatment. Alzheimer Dis Assoc Disord. 2006;20(4):263-268. 39. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007;120(5):388-397. 40. Beier MT. Treatment strategies for the behavioral symptoms of Alzheimer’s disease: focus on early pharmacologic intervention. Pharmacotherapy. 2007;27(3):399-411. 41. Lambert MP, Barlow AK, Chromy BA, et al. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A. 1998;95(11):6448-6453. 42. Yang F, Lim GP, Begum AN, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892-5901. 18 PATIENT CARE NEUROLOGY & PSYCHIATRY www.patientcareonline.com http://www.patientcareonline.com

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Patient Care Neurology & Psychiatry - November 2007 Contents Research Digest Medicine in the News The 15-Minute Visit Dementia workup and treatment: Do the drugs really work? Help for Your Patients Who Suffer from Specific Phobias Clinical Clips Case & Comment The Science of Healing Classified Advertising

Patient Care Neurology & Psychiatry - November 2007

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