Treatment of Alzheimer's disease

doi:10.1017/CBO9780511544873.033

32 - Treatment of Alzheimer's disease

from Part IV - Alzheimer's disease

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Mary Sano: Affiliation:
Alzheimer's Disease Research Center, Department of Psychiatry, Mount Sinai School of Medicine, New York NY

Book contents

Get access

Summary

Overview

Over the past decade medications have been approved for the treatment of Alzheimer's disease (AD). The first of these worked via cholinergic stimulation, and targeted the symptoms of attention and memory. More recently Memantine, an NMDA receptor antagonist, has been added to the list of approved medications for AD. These treatments provide symptomatic benefits. Initiative for new therapeutics target the characteristic neuropathological features of AD or other biological mechanisms that may reflect the etiology of the disease in the hope of identifying preventative or curative agents.

Research into treatment of AD tends to focus on interventions at the earliest stage of the disease and the concept of mild cognitive impairment (MCI), a prodrome to dementia, has become the target of many interventions. This approach has the added challenge of determining diagnostic specificity of an entity, which does not yet constitute a diagnosis. At the same time, interest in treating the more impaired patient has grown with the approval of the first drug with an indication for moderate to severe AD and with new studies examining cholinesterase inhibitors in more advanced patients.

Awareness that AD may coexist with other CNS diseases or be difficult to distinguish from dementia of other etiologies may have contributed to the interest in treatments for individuals with other conditions including vascular and mixed dementia.

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 459 - 470

DOI: https://doi.org/10.1017/CBO9780511544873.033 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

AD2000 Collaborative Group (2004). Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomized double-blind trial. Lancet, 363, 2105–15CrossRef

Aisen, P.Davis, S., , K. L., Berg, J. D.et al. (2000). A randomized controlled trial of prednisone in Alzheimer's disease. Neurology, 54, 588–92CrossRef Google Scholar PubMed

Aisen, P. S., Egelko, S., Andrews, H.et al. (2003a). A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am. J. Geriatr. Psychiatr., 11(2), 246–9CrossRef Google Scholar

Aisen, P. S., Schafer, K. A., Grundman, M.et al. (2003b). Alzheimer's disease cooperative study. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. J. Am. Med. Assoc., 289(21), 2819–26CrossRef Google Scholar

Arends, Y. M., Duyckaerts, C., Rozemuller, J. M., Eikelenboom, P. & Hauw, J. (2000). Microglia, amyloid and dementia in Alzheimer's disease. A correlative study. Neurobiol. Agin., 21, 39–47CrossRef Google Scholar PubMed

Bales, K. R., Verina, T., Dodel, R. C.et al. (1997). Lack of apolipoprotein E dramatically reduces amyloid b-peptide deposition. Nat. Gene., 17, 263–4CrossRef Google Scholar

Barkats, M., Venault, P., Christen, Y. & Cohen-Salmon, C. (1995). Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains. Life Sci., 56, 213–22CrossRef Google Scholar PubMed

Birks, J., Grimley, E. V. & Dongen, M. (2002). Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst. Rev., (4), CD003120CrossRef Google Scholar

Birks, J., Grimley Evans, J., Iakovidou, V. & Tsolaki, M. (2003). Rivastigmine for Alzheimer's disease. [systematic review] Cochrane Dementia and Cognitive Improvement Group. Cochrane Database of Systematic Reviews, 2Google Scholar

Birks, J. S. & Harvey, R. (2003). Donepezil for dementia due to Alzheimer's disease. Cochrane Database of Systematic Reviews, (3), CD001190CrossRef Google Scholar PubMed

Brookmeyer, R., Gray, S. & Kawas, C. (1998). Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am. J. Public Hlth., 88, 1337–42CrossRef Google Scholar PubMed

Butterfield, D. A. (2002). Amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res., 36, 1307–13CrossRef Google Scholar PubMed

Caro, J. J., Salas, M., Ward, A., Getsios, D. & Mehnert, A. & AHEAD Study Group (2002). Assessment of Health Economics in Alzheimer's Disease Economic analysis of galantamine, a cholinesterase inhibitor, in the treatment of patients with mild to moderate Alzheimer's disease in the Netherlands. Dement. Geriatr. Cogn. Disord., 14(2), 84–9CrossRef Google Scholar

Clarke, R., Smith, A. D., Jobst, K. A.et al. (1998). Vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch. Neurol., 55, 1449–55CrossRef Google Scholar PubMed

Eikelenboom, P. & Gool, W. A. (2004). Neuroinflammatory perspectives on the two faces of Alzheimer's disease. J. Neural. Transm., 111, 281–94CrossRef Google Scholar PubMed

Engelhart, M. J., Geerlings, M. I., Ruitenberg, A.et al. (2002). Dietary intake of antioxidants and risk of Alzheimer disease. J. Am. Med. Assoc., 287(24), 3223–9CrossRef Google Scholar PubMed

Erkinjuntti, T., Kurz, A., Gauthier, S., Bullock, R., Lilienfeld, S. & Damaraju, C. V. (2002). Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet, 359, 1283–90CrossRef Google Scholar PubMed

Etminan, M., Gill, S. & Samii, A. (2003). Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. Br. Med. J., 327, 128CrossRef Google Scholar PubMed

Gandy, S, ., Martins, R. N. & Buxbaum, J. (2003). Molecular and cellular basis for anti-amyloid therapy in Alzheimer disease. Alzheimer. Dis. Assoc. Disord., 17, 259–66CrossRef Google Scholar

Geldmacher, D. (1997). Donepezil (Aricept) therapy for Alzheimer's disease. Compr. Ther., 23(7), 492–3Google Scholar PubMed

Geldmacher, D. S., Provenzano, G., McRae, T., Mastey, V. & Ieni, D. E. G. Jr. (2003). Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. J. Am. Geriatr. Soc., 51, 937–44CrossRef Google Scholar PubMed

Heart Protection Study Collaborative Group (2002). MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet, 360, 23–33CrossRef

in t' Veld, B. A., Ruitenberg, A., Hofman, , et al. (2001). Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N. Engl. J. Med., 345, 1515–21CrossRef Google Scholar PubMed

Jick, H., Zornberg, G. L., Jick, S. S., Seshadri, S. & Drachman, D. A. (2000). Statins and the risk of dementia. Lancet, 356, 1627–31CrossRef Google Scholar

Kieburtzk, K., McDermott, M., Como, P.et al. (1994). The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group. Neurology, 44, 1756–9CrossRef Google Scholar

Kirschstein, R. (2002). Disease-specific estimates of direct and indirect costs of illness and NIH support. National Institutes of Health, 6–11. http://www1.od.nih.gov/osp/ospp/ecostudies/COIreportwebGoogle Scholar

Knapp, M. J., Knopman, D. S., Solomon, P. R., Pendlebury, W. W., Davis, C. S., Gracon, S. I. (1994). A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group. J. Am. Med. Assoc., 271(13), 985–91CrossRef Google Scholar PubMed

Knopman, D., Schneider, L., Davis, K.et al. (1996). Long-term tacrine (Cognex) treatment: effects on nursing home placement and mortality, Tacrine Study Group. Neurology, 47(1), 166–77CrossRef Google Scholar

Bars, P. L., Katz, M. M., Berman, N., Itil, T. M., Freedman, A. M. & Schatzberg, A. F. (1997). A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. J. Am. Med. Assoc., 278, 1327–32Google Scholar PubMed

Li, F., Calingasan, N., Yo, F.et al. (2004). Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J. Neurochem., 89, 1308–12CrossRef Google Scholar PubMed

Logsdon, R. G., Gibbons, L. E., McCurry, S. M. & Teri, L. (2002). Assessing quality of life in older adults with cognitive impairment. Psychosom. Med., 64(3), 510–19CrossRef Google Scholar PubMed

Marin, D., Amaya, K., Casciano, R.et al. (2003). Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer's disease. Int. Psychogeriatr., 15(4), 385–98CrossRef Google Scholar PubMed

Martin, B. K., Meinert, C. L. & Breitner, J. C. S. (2002). Double placebo design in a prevention trial for Alzheimer's disease. Controlled Clin. Trial., 23, 93–9CrossRef Google Scholar

McCaddon, A., Davies, G., Hudson, P., Tandy, S. & Cattell, H. (1998). Total serum homocysteine in senile dementia of Alzheimer type. Int. J. Geriatr. Psychiatr., 13, 235–93.0.CO;2-8>CrossRef Google Scholar PubMed

Morris, M. C., Evans, D. A., Bienias, J. L.et al. (2002). Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. Am. Med. Assoc., 287, 3230–7CrossRef Google Scholar

Nilsson, I. N., Bales, K. R., DiCarlo, G.et al. (2001). Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease. J. Neurosci., 21(5), 1444–51CrossRef Google Scholar

Oken, B. S., Storzbach, D. M. & Kaye, J. A. (1998). The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch. Neurol., 55, 1409–15CrossRef Google Scholar PubMed

Olin, J. & Schneider, L. (2004). Galantamine for dementia due to Alzheimer's disease. [systematic review] Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews, 2

Peskind, E. R., Potkin, S. G., Pomara, N., McDonald, D., Xie, Y. & Gergel, I. (2004). Memantine monotherapy is elective and safe for the treatment of mild to moderate AD. Am. J. Geriatr. Psychiatry.Google Scholar

Reines, S. A., Block, G. A., Morris, J. C.et al. (2004). Rofecoxib Protocol 091 Study Group. No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology, 62(1), 66–71CrossRef Google Scholar

Reisberg, B., Doody, R., Stoffler, A., Schmitt, F., Ferris, S. & Mobius, H. J. Memantine Study Group (2003). Memantine in moderate-to-severe Alzheimer's disease. N. Engl. J. Med. 348(14), 1333–41CrossRef Google Scholar PubMed

Rockwood, K., Kirkland, S., Hogan, D. B.et al. (2002). Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch. Neurol., 59, 223–7CrossRef Google Scholar PubMed

Rogers, J., Kirby, L. C., Hempelman, S. R.et al. (1993). Clinical trial of indomethacin in Alzheimer's disease. Neurology, 43, 1609–11CrossRef Google Scholar PubMed

Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R. & Friedhoff, L. T. Donepezil Study Group (1998). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 50(1), 136–45CrossRef Google Scholar PubMed

Sano, M. (2002). Prevention of Alzheimer's disease: the problem of the drugs and the designs. Curr. Neurol. Neurosci. Rep., 2, 392–9CrossRef Google Scholar

Sano, M., Ernesto, C., Thomas, R. G.et al. The Alzheimer's Disease Cooperative Study. (1997). A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N. Engl. J. Med., 24(336), 1216–22CrossRef Google Scholar

Sano, M., Wilcock, G., Baelen, B. & Kavanagh, S. (2003). The effects of galantamine treatment on caregiver time in Alzheimer's disease. Int. J. Geriatr. Psychiatr., 18, 1–9CrossRef Google Scholar PubMed

Scharf, S., Mander, A., Ugoni, A., Vajda, F. & Christophidis, N. (1999). A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology, 53, 197–201CrossRef Google Scholar PubMed

Scholtyssek, H., Damerau, W., Wessel, R. & Schimke, I. (1997). Antioxidative activity of ginkgolides against superoxide in an aprotic environment. Chem.-Biol. Interaction., 106, 83–90CrossRef Google Scholar

Seshadri, S., Beiser, A., Selhub, J.et al. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N. Engl. J. Med., 14(346), 476–83CrossRef Google Scholar

Shepherd, J., Blauw, G. J., Murphy, M. B.et al. PROSPER study group (2002). PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet, 360, 1623–30CrossRef Google Scholar PubMed

Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., Gergel, I.; Memantine Study Group (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. J. Am. Med. Assoc., 291(3), 317–24CrossRef Google Scholar PubMed

Torian, I., Davidson, E., Fulop, G., Sell, I. & Fillit, H. (1992). The effect of dementia on acute care in a geriatric medical unit. Int. Psychogeriatr., 4(2), 231–9CrossRef Google Scholar

Dongen, M. C., Rossum, E., Kessels, A. G., Sielhorst, H. J. & Knipschild, P. G. (2000). 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., 48, 1183–94CrossRef Google Scholar PubMed

Visser, H., Thal, L., Ferris, S. et al. (2003). A randomized double-blind placebo controlled trial of Rofecoxib in patients with MCI. ACNP Annual Meeting 12-10-03. San Juan, Puerto Rico

Weggen, S., Eriksen, J. L., Das, P.et al. (2001). A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature, 414, 212–16CrossRef Google Scholar PubMed

Wilkinson, D., Doody, R., Helme, R.et al. (2003). Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology, 61(4), 479–86CrossRef Google Scholar PubMed

Winblad, B., & Poritis, N. (1999). Memantine in severe dementia: results of the 9M-Best Study (benefit and efficacy in severely demented patients during treatment with memantine). Int. J. Geriatr. Psychiatr., 14(12), 135–463.0.CO;2-0>CrossRef Google Scholar

Winblad, B., Engedal, K., Soininen, H.et al. (2001). A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57, 489–95CrossRef Google Scholar PubMed

Wolozin, B., Kellman, W., Ruosseau, P., Celesia, G. G. & Siegel, G. (2000). Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol., 57, 1439–43CrossRef Google Scholar PubMed

Zandi, P. P., Anthony, J. C., Hayden, K. M., Mehta, K., Mayer, L. & Breitner, J. C; Cache County Study Investigators (2002). Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology, 59, 880–6CrossRef Google Scholar

Zandi, P. P., Anthony, J. C., Khachaturian, A. S.et al. Cache County Study Group (2004). Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. Arch. Neurol., 61, 82–8CrossRef Google Scholar PubMed

Book contents

32 - Treatment of Alzheimer's disease

Summary

Access options

References

Save book to Kindle

Save book to Dropbox

Save book to Google Drive