Background: A number of pharmacologic and nonpharmacologic interventions have been proposed to treat patients with dementia. Determining which treatments are the most promising can be difficult. Hogan and colleagues searched the medical literature for articles that addressed management of Alzheimer disease and other dementias, as part of the evidence-based guidelines for the Third Canadian Conference on the Diagnosis and Treatment of Dementia.

The Study: The authors selected articles published between January 1996 and December 2005 to review, and wrote recommendations based on this review. They continued searching for relevant articles published from January 2006 to April 2008 to refine the earlier recommendations. Overall, 954 articles were reviewed.

Results: Although environmental adjustments can help control dementia-related symptoms, such as agitation or anxiety, insufficient evidence exists to show that these approaches slow rates of cognitive or functional decline. However, good evidence exists that individualized exercise programs can slow the progression of dementia. One study reported that, compared with routine medical care, one hour of exercise twice a week significantly slowed functional decline in nursing home patients with Alzheimer disease.

Several pharmacologic therapies are available for patients with mild Alzheimer disease. Three cholinesterase inhibitors (i.e., donepezil [Aricept], galantamine [Razadyne)], and rivastigmine [Exelon]) have similar degrees of benefit. They may slow, but not stop, cognitive decline. However, long-term clinical benefit is modest because most trials have lasted for 26 weeks or less and tend to rely on technical measurements (e.g., the Alzheimer's Disease Assessment Scale) rather than patient-centered outcomes, such as improvements in quality of life or functional outcomes.

Although it is not approved for treating patients with vascular dementia, some studies have shown that donepezil can improve outcomes in this population. Galantamine may help treat Alzheimer disease with a vascular component. When starting cholinesterase inhibitors, patients should be monitored for adverse effects and reevaluated in three to six months to determine their response to therapy. Gastrointestinal issues (e.g., nausea, vomiting, diarrhea, anorexia) are the most common adverse effects, but are transient and dose-related. Oral rivastigmine had the highest rate of nausea (37 percent), although less nausea is reported with the transdermal patch. Antiemetics (e.g., prochlorperazine [formerly Compazine]) should be avoided because of possible anti-cholinergic properties and adverse cognitive effects.

The N-methyl-d-aspartate receptor antagonist memantine (Namenda) may be used as monotherapy or adjunctive therapy with a cholinesterase inhibitor for treating moderate to severe Alzheimer disease. Combination therapy appears to be well tolerated, but there are conflicting data as to whether this combination will improve patient outcomes. Memantine is contra-indicated in patients with severe renal impairment, and should be used with caution in patients with a history of seizures or cardiovascular disease. Related drugs, such as amantadine (Symmetrel), ketamine (Ketalar), and dextromethorphan, can cause additive effects of both drugs if used with memantine and should be avoided.

Conclusion: A recurring exercise regimen is the best non-pharmacologic option to reduce progression of Alzheimer disease. Cholinesterase inhibitors show similar degrees of benefit, but their effect beyond 26 weeks of use has not been clearly established. Donepezil and galantamine may also benefit patients with vascular-related dementia. Memantine may be more useful with more severe dementia, but it is unclear whether combining it with a cholinesterase inhibitor will further improve outcomes.