Utilizing combination therapy in the treatment of Alzheimer’s disease

Alzheimer’s disease may not yet be curable, but it is treatable. Two classes of drugs with differing mechanisms of action have received Food and Drug Administration approval for the treatment of Alzheimer’s disease: the cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine (Ebixa®, Lundbeck; Namenda®, Forest Laboratories). Alzheimer’s disease research directed at increasing the understanding of the underlying disease process has led to the identification of several other potential targets for drug development strategies. Due to the complexity of the disease, it is possible that combination therapy – concomitant use of agents with nonoverlapping or even synergistic mechanisms of action – may represent the best means available to enhance treatment effectiveness. This review evaluates the available data on combination therapy in Alzheimer’s disease and provides an expert opinion on the use and implementation of combination therapy in clinical practice.

[1]  L. Thal,et al.  Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study , 2004, JAMA.

[2]  S. Potkin,et al.  O1-05-04 Memantine monotherapy is effective and safe for the treatment of mild to moderate Alzheimer's disease: a randomized controlled trial , 2004, Neurobiology of Aging.

[3]  JoAnn E Manson,et al.  Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. , 2004, JAMA.

[4]  D. Foley,et al.  Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. , 2004, American journal of epidemiology.

[5]  J. Karlawish Donepezil Delay to Nursing Home Placement Study is Flawed , 2004, Journal of the American Geriatrics Society.

[6]  T. Finucane Another Advertisement for Donepezil , 2004, Journal of The American Geriatrics Society.

[7]  D. Royall Donepezil's Effects Remain Uncertain , 2004, Journal of The American Geriatrics Society.

[8]  E. Peskind,et al.  The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial. , 2004, Archives of neurology.

[9]  Pierre N Tariot,et al.  Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. , 2004, JAMA.

[10]  Jeffrey L. Cummings,et al.  Cholinesterase Inhibitor Therapies and Neuropsychiatric Manifestations of Alzheimer’s Disease , 2003, Dementia and Geriatric Cognitive Disorders.

[11]  B. Reisberg,et al.  P.4.006 Long-term efficacy and safety benefits from treatment with the NMDA antagonist memantine: results of a 24-week, open-label extension study in moderate to severe Alzheimer's disease , 2003, European Neuropsychopharmacology.

[12]  J. Kornhuber,et al.  Memantine in moderate-to-severe Alzheimer's disease. , 2003, The New England journal of medicine.

[13]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[14]  M. Etminan,et al.  Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies , 2003, BMJ : British Medical Journal.

[15]  Robert B Wallace,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. , 2003, JAMA.

[16]  C. Kooperberg,et al.  Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. , 2003, JAMA.

[17]  D. Geldmacher Alzheimer's Disease: Current Pharmacotherapy in the Context of Patient and Family Needs , 2003, Journal of the American Geriatrics Society.

[18]  N. Tabet,et al.  Ibuprofen for Alzheimer's disease. , 2003, The Cochrane database of systematic reviews.

[19]  H. Nagaraja,et al.  Combination Therapy of Donepezil and Vitamin E in Alzheimer Disease , 2003, Alzheimer disease and associated disorders.

[20]  S. Hartmann,et al.  Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy , 2003, International clinical psychopharmacology.

[21]  R. Mayeux,et al.  Antioxidant vitamin intake and risk of Alzheimer disease. , 2003, Archives of neurology.

[22]  L. Flicker,et al.  Selegiline for Alzheimer's disease. , 2003, The Cochrane database of systematic reviews.

[23]  B. Vellas,et al.  No additional benefit of HRT on response to rivastigmine in menopausal women with AD , 2003, Neurology.

[24]  A. Kurz,et al.  Galantamine Provides Sustained Benefits in Patients with ‘Advanced Moderate’ Alzheimer’s Disease for at Least 12 Months , 2003, Dementia and Geriatric Cognitive Disorders.

[25]  H. Steinbusch,et al.  Antioxidants and Alzheimer's disease: from bench to bedside (and back again) , 2002, Current opinion in clinical nutrition and metabolic care.

[26]  M. Farlow,et al.  GALANTAMINE PROVIDES BROAD BENEFITS IN PATIENTS WITH ‘ADVANCED MODERATE’ ALZHEIMER'S DISEASE (MMSE ≤12) FOR UP TO SIX MONTHS , 2002, International journal of clinical practice.

[27]  J. Witteman,et al.  Dietary intake of antioxidants and risk of Alzheimer disease. , 2002, JAMA.

[28]  D. Bennett,et al.  Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study , 2022 .

[29]  K. Krishnan,et al.  Long-term effects of rivastigmine in moderately severe Alzheimer's disease Does early initiation of therapy offer sustained benefits? , 2002, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[30]  P. Aisen Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer's disease. , 2002, Journal of pain and symptom management.

[31]  A Whitehead,et al.  The effect of selegiline in the treatment of people with Alzheimer's disease: a meta‐analysis of published trials , 2002, International journal of geriatric psychiatry.

[32]  Steven G Potkin,et al.  The ABC of Alzheimer's Disease: ADL and Improving Day-to-Day Functioning of Patients , 2002, International Psychogeriatrics.

[33]  A. Hofman,et al.  Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. , 2001, The New England journal of medicine.

[34]  P. Zandi,et al.  Do NSAIDs prevent Alzheimer’s disease? And, if so, why? The epidemiological evidence , 2001, Neurobiology of Aging.

[35]  L. Beckett,et al.  Annual Incidence of Alzheimer Disease in the United States Projected to the Years 2000 Through 2050 , 2001, Alzheimer disease and associated disorders.

[36]  H. Feldman,et al.  A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease , 2001, Neurology.

[37]  C. Schweiger [Statins and the risk of dementia]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[38]  B. Gordon,et al.  Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. , 2001, Archives of neurology.

[39]  G. Wilcock,et al.  Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial , 2000, BMJ : British Medical Journal.

[40]  D. Praticò,et al.  Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. , 2000, The American journal of medicine.

[41]  G. Celesia,et al.  Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. , 2000, Archives of neurology.

[42]  L. Wilkins Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension , 2000, Neurology.

[43]  P. Tariot,et al.  A 5-month, randomized, placebo-controlled trial of galantamine in AD , 2000, Neurology.

[44]  E. Peskind,et al.  Galantamine in AD , 2000, Neurology.

[45]  C. Plata-salamán,et al.  Inflammation and Alzheimer’s disease , 2000, Neurobiology of Aging.

[46]  R. Doody,et al.  Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study , 2000, European Neuropsychopharmacology.

[47]  Anthony Gamst,et al.  Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial , 2000 .

[48]  W. Danysz,et al.  No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. , 2000, Life sciences.

[49]  Y. Christen,et al.  Oxidative stress and Alzheimer disease. , 2000, The American journal of clinical nutrition.

[50]  Šimon Scharf,et al.  A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease , 1999, Neurology.

[51]  A. Doble The role of excitotoxicity in neurodegenerative disease: implications for therapy. , 1999 .

[52]  B. Winblad,et al.  Memantine in severe dementia: results of the 9M‐best study (benefit and efficacy in severly demented patients during treatment with memantine) , 1999, International journal of geriatric psychiatry.

[53]  L. Schneider,et al.  Systematic review of the efficacy of rivastigmine for patients with Alzheimer's disease , 1998 .

[54]  R Brookmeyer,et al.  Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. , 1998, American journal of public health.

[55]  N. Delanty,et al.  Risk of Alzheimer's disease and duration of NSAID use , 1998, Neurology.

[56]  R. Mohs,et al.  Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. , 1998, Archives of internal medicine.

[57]  L. Amaducci,et al.  Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging , 1998, Neurology.

[58]  R. Mohs,et al.  A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease , 1998, Neurology.

[59]  J. Olney,et al.  Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. , 1997, Archives of neurology.

[60]  P Woodbury,et al.  A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. , 1997, The New England journal of medicine.

[61]  Yaakov Stern,et al.  Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease , 1996, The Lancet.

[62]  L. Schneider,et al.  Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease , 1996, Neurology.

[63]  P. Mcgeer,et al.  Anti‐Inflammatory Drugs in the Fight against Alzheimer's Disease a , 1996, Annals of the New York Academy of Sciences.

[64]  K. Davis,et al.  l-Deprenyl and physostigmine for the treatment of Alzheimer's disease , 1995, Psychiatry Research.

[65]  P. Mcgeer,et al.  The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases , 1995, Brain Research Reviews.

[66]  L. W. Buckalew,et al.  Survey of the Nature and Prevalence of Patients' Noncompliance and Implications for Intervention , 1995, Psychological Reports.

[67]  L. Schneider,et al.  A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in Alzheimer's disease. , 1993, The American journal of psychiatry.

[68]  M. Albert,et al.  Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. , 1989, JAMA.

[69]  J. Penney,et al.  Glutamate transmission and toxicity in alzheimer's disease , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[70]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[71]  Deborah Gustafson,et al.  Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. , 2004, Archives of neurology.

[72]  S. Wiebe,et al.  Report of the Quality Standards Subcommittee of the American Academy of Neurology, in Association with the American Epilepsy Society and the American Association of Neurological Surgeons , 2003 .

[73]  B. Miller,et al.  CME Practice parameter : Diagnosis of dementia ( an evidence-based review ) Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2001 .

[74]  G. Wilcock,et al.  Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. , 2000, BMJ.

[75]  Y. Agid,et al.  Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. , 1999, BMJ.

[76]  Rachelle S. Doody,et al.  DONEPEZIL STUDY GROUP. A 24-WEEK, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL OF DONEPEZIL IN PATIENTS WITH ALZHEIMER'S DIS-EASE , 1998 .