The strength of evidence (high, moderate, low, insufficient evidence to determine benefits or risks) and strength of recommendations (strong, weak, I recommendation) are defined at the end of the "Major Recommendations."
Recommendation 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. (Grade: weak recommendation, moderate-quality evidence.)
The decision to initiate therapy should be based on evaluation of benefits and risks associated with an individual patient. In particular, in more advanced dementia, family or other decision makers may not view stabilization or slowing of decline as a desirable goal if quality of life is judged to be poor. All of the drugs have known adverse events, and the decision to manage patients with dementia should balance harms against modest or even no benefit. Although the evidence shows statistically significant benefits of treatment with some cholinesterase inhibitors and memantine for all kinds of dementia, these benefits, on average, are not clinically significant for cognition and are modest for global assessments. However, limited evidence suggests, but does not demonstrate conclusively, that a subgroup of patients achieves clinically important improvements. Currently, there is no way to predict which patients might have a clinically important response. Therefore, the evidence does not support prescribing these medications for every patient with dementia.
Evidence is insufficient to determine the optimal duration of therapy. A beneficial effect, if any, would generally be observed within 3 months on the basis of duration of trials. This effect could be an improvement or stabilization. In addition, no evidence demonstrates when it is appropriate to stop the treatment if the patient becomes unresponsive or shows decline in various domains of dementia. However, if slowing decline is no longer a goal, treatment with memantine or a cholinesterase inhibitor is no longer appropriate.
Recommendation 2: Clinicians should base the choice of pharmacologic agents on tolerability, adverse effect profile, ease of use, and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.)
Because few trials compare one drug with another, evidence about effectiveness is insufficient to support the choice of specific drugs for the treatment of dementia. Therefore, tolerability, adverse effect profile, ease of use, and cost of medication are reasonable criteria to help select a treatment. For example, when the benefits and harms related to a drug are being evaluated, the severe side effects associated with tacrine make it an unreasonable choice.
Cholinesterase inhibitors are approved for treatment of mild to moderate dementia, and memantine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe Alzheimer disease. Patients with mild vascular dementia have shown mild benefit from memantine. However, memantine use in mild Alzheimer disease has not been well studied. Major contraindications of cholinesterase inhibitors and memantine include, but are not limited to, uncontrolled asthma, angle-closure glaucoma, the sick sinus syndrome, and left bundle-branch block.
See the original guideline document for recommendations for further research.
Definitions:
This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system adopted from the classification developed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) workgroup.
American College of Physicians' Clinical Practice Guidelines Grading System* |
Quality of Evidence |
Strength of Recommendation |
|
Benefits Clearly Outweigh Risks and Burden OR Risks and Burden Clearly Outweigh Benefits |
Benefits Finely Balanced with Risks and Burden |
High |
Strong |
Weak |
Moderate |
Strong |
Weak |
Low |
Strong |
Weak |
Insufficient evidence to determine net benefits or risks |
I recommendation |
*Adopted from the classification developed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) workgroup.