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Cover of Pharmacological Treatment of Dementia

Pharmacological Treatment of Dementia

Evidence Reports/Technology Assessments, No. 97

Investigators: , PhD, , PhD, , BA, , MD, , MSc, , MD, , BA, , MD, and , PhD.

Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 04-E018-2ISBN-10: 1-58763-151-2

Structured Abstract


Dementia is a chronic progressive disease with no known cure. It affects cognition, behavior/mood, physical functions and activities of daily living, and caregiver burden. Therapeutic interventions for dementia aim to affect these domains.


To review the evidence and answer the questions: Does pharmacotherapy for dementia syndromes improve cognitive symptoms and outcomes? Does pharmacotherapy delay cognitive deterioration or delay disease onset of dementia syndromes? Are certain drugs, including alternative medicines (non-pharmaceutical), more effective than others? Do certain patient populations benefit more from pharmacotherapy than others? What is the evidence base for the treatment of ischemic vascular dementia (VaD)?

Data sources:

Studies were identified by searching the Cochrane Central trial registry, MEDLINE® , PreMedline®, EMBASE, AMED, CINAHL®, Ageline, and PsycINFO.

Study selection:

English-language randomized controlled trials were selected if they evaluated pharmacological agents for adults with a diagnosis of dementia according to the criteria of International Classification of Diseases (ICD), Diagnostic and Statistical Manual of Mental Disorders (DSM) or National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Crossover trials and studies with a quality score < 3 on the Jadad Scale were excluded.

Data extraction:

Data were extracted on type of dementia, severity of disease, setting, regimen of pharmacological agents, study duration, main outcome measures, adverse effects, and results. The quality of studies was assessed, and the quality of adverse effect reporting was assessed. Effect sizes were calculated and data were pooled when appropriate.

Data synthesis:

(1) Efficacy: One hundred and eighty-six Randomized Controlled Trials (RCTs) evaluated 97 drugs. As expected the findings varied with the dementia population and the specific outcomes in the various domains. Those pharmacological agents that showed a consistent effect of benefit are as follows: A) Global assessment was improved by donepezil, galantamine, rivastigmine, velnacrine, cerebrolysin and idebenone; B) Cognition (general and specific) was improved by donepezil, galantamine, metrifonate (this drug has been withdrawn from use in North America because of safety concerns), nicergoline, physosligmine, rivastigmine, velnacrine, memantine, cerebrolysin, ginkgo biloba, idebenone and propentofylline; C) Behavior/mood was improved by haloperidol; D) Quality of life/Activities of Daily Living (ADL) was improved by donepezil, galantamine and posatirelin. In general, caregiver burden and quality of life/ADL were not frequently evaluated. (2) Delay disease: Cerebrolysin, selegiline plus vitamin E, and donepezil showed some significant effects in delaying disease progress in patients with mild to moderate and moderately severe Alzheimer's disease. (3) Head to head comparisons: Superiority was seen for sulphomucopolysaccharides over CDP-choline, donepezil over vitamin E, antagonic-stress over nicergoline, antagonic-stress over meclofenoxate, posatirelin over citicoline, and pyritinol over hydergine. (4) Patient populations: Stratified analyses included: age, gender, Apolipoprotein E (APOE) genotype, disease type, disease severity, race by location, care dependence, and presence of depression. Single populations of dementia subjects with Down's syndrome, and depression were evaluated. Evidence was inconclusive for this question. (5) Ischemic VaD: A total of 20 pharmacological interventions in 29 studies were applied to vascular dementias. Differences were suggested between multi-infarct dementia (MID) and Alzheimer's disease (AD) for 5′ -MTHF-trazodone, AD and VaD for citalopram, and AD and MID for Ginkgo biloba. Trials with VaD patients showed effects for memantine, nicergoline, pentoxyfylline, idebenone, donepezil and cerebrolysin.


Pharmacotherapy for dementia can improve symptoms and outcomes. Adverse events should be more systematically reported. Few studies evaluated delay in either disease onset or progression, but there was some evidence suggesting delay in progression. Few studies compared drugs with other drugs. Due to poor evaluation, data was limited to consider efficacy of pharmacotherapy in different subgroups of patients. Some agents have been shown to be effective in VaD patients.


Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0020. Prepared by: McMaster University Evidence-based Practice Center, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.

Suggested citation:

Santaguida PS, Raina P, Booker L, Patterson C, Baldassarre F, Cowan D, Gauld M, Levine M, Unsal A. Pharmacological Treatment of Dementia. Evidence Report/Technology Assessment No. 97 (Prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E018-2. Rockville, MD: Agency for Healthcare Research and Quality. April 2004.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and braoden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use and access. The information helps health care decisionmakers - patients and clinicians, health system leaders, and policymakers - make more informed decisions and improve the quality of health care services.

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.


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Bookshelf ID: NBK37314


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