When are cholinesterase inhibitors indicated for cognitive changes in patients with dementia?

From the Guidelines

Cholinesterase inhibitors are indicated for mild to moderate cognitive changes associated with Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, and vascular dementia, as they may temporarily improve symptoms or slow decline for 6-12 months in approximately 50% of patients 1.

Key Considerations

• These medications, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), work by preventing the breakdown of acetylcholine, a neurotransmitter important for memory and thinking.
• They are typically started at low doses and gradually increased to minimize side effects such as nausea, vomiting, and diarrhea.
• Donepezil is usually initiated at 5mg daily and may be increased to 10mg after 4-6 weeks; rivastigmine is started at 1.5mg twice daily and gradually increased to 3-6mg twice daily; galantamine begins at 4mg twice daily and can be titrated up to 12mg twice daily.
• The decision to initiate therapy should be based on evaluation of benefits and risks associated with an individual patient, taking into account their preferences, prior expressed wishes, and collaboration with family or substitute decision makers 1.

Important Guidelines

• For individuals taking a cholinesterase inhibitor for Alzheimer’s disease, Parkinson’s disease dementia, Lewy body dementia, or vascular dementia for >12 months, discontinuation should be considered if there has been a clinically meaningful worsening of dementia, no clinically meaningful benefit was observed, or the individual has severe or end-stage dementia 1.
• Cholinesterase inhibitors should not be discontinued in individuals who currently have clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized, unless these symptoms appear to have been worsened by the initiation of a ChEI or an increase in ChEI dose 1.
• Individuals who have had a clinically meaningful reduction in neuropsychiatric symptoms with cognitive enhancers should continue to be treated with the cognitive enhancer even if there is evidence of cognitive and functional decline 1.

From the FDA Drug Label

Donepezil is an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer’s type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer’s Disease (1) Galantamine is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer's type (1)

Cholinesterase inhibitors are indicated for cognitive changes associated with dementia of the Alzheimer's type, specifically:

• Mild, moderate, and severe Alzheimer's Disease for donepezil 2 and 2
• Mild to moderate dementia of the Alzheimer's type for galantamine 3

From the Research

Indications for Cholinesterase Inhibitors

Cholinesterase inhibitors are indicated for the treatment of cognitive changes in patients with:

• Mild to moderate Alzheimer's disease 4, 5
• Lewy Body dementia (LBD) and Parkinson's disease dementia (PDD), with rivastigmine being the only approved cholinesterase inhibitor for PDD 6
• Vascular dementia (VaD), although the evidence is limited and the interpretation of findings is challenging due to the heterogeneity of patients and scales used 6

Benefits of Cholinesterase Inhibitors

The benefits of cholinesterase inhibitors include:

• Improvement in cognitive function, with an average improvement of -2.7 points on the ADAS-Cog Scale 5
• Improvement in global clinical state, activities of daily living, and behavior 5
• Delay in nursing home admission and slower rates of cognitive and functional impairment when initiated early and used persistently 7

Side Effects and Tolerability

Cholinesterase inhibitors are generally well-tolerated, but can cause:

• Mild to moderate cholinergic side effects, such as nausea, vomiting, and diarrhea 5, 6
• Increased risk of cardio and cerebrovascular events with rivastigmine in VaD 6
• Syncope and bradycardia, particularly in more susceptible patients with advanced disease 7

Use Across All Stages of Alzheimer's Disease

Cholinesterase inhibitors can be used across all stages of Alzheimer's disease, including:

• Early stages, where they can delay nursing home admission and slow cognitive and functional decline 7
• Moderate to severe stages, where higher doses or combination therapy with memantine may be recommended 7
• Terminal stages, where attempts to discontinue medications not necessary for quality of life should be made 7