From the Guidelines
The first-line treatment for Alzheimer's disease typically involves acetylcholinesterase inhibitors (AChEIs) such as donepezil, rivastigmine, or galantamine, as they have been shown to improve cognitive function and slow decline in patients with mild to moderate dementia. These medications are usually started at low doses and gradually increased to therapeutic levels. For example, donepezil is commonly initiated at 5 mg once daily and may be increased to 10 mg daily after 4-6 weeks if well tolerated, as supported by studies such as 1.
Key Considerations
- The choice of pharmacologic agent should be based on tolerability, adverse effect profile, ease of use, and cost of medication, as recommended by 1 and 1.
- Memantine, an NMDA receptor antagonist, may be added to an AChEI for moderate to severe Alzheimer's, often at a starting dose of 5 mg daily and titrated up to 10 mg twice daily.
- Treatment should be accompanied by regular monitoring for side effects, which can include nausea, vomiting, diarrhea, and sleep disturbances.
- Non-pharmacological approaches such as cognitive stimulation, physical activity, and caregiver support are also essential components of comprehensive Alzheimer's care.
Important Factors
- The evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia, as noted in 1 and 1.
- Further research is needed to evaluate the effectiveness of pharmacologic therapy for dementia and to assess whether treatment affects outcomes, such as institutionalization, as highlighted in 1 and 1.
- The use of AChEIs and memantine has been shown to improve global cognitive function by approximately 1- to 3-point differences on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-cog), as reported in 1.
From the FDA Drug Label
The effectiveness of donepezil hydrochloride in the treatment of patients with moderate to severe Alzheimer’s disease was established in studies employing doses of 10 mg/day and 23 mg/day The effectiveness of donepezil hydrochloride as a treatment for severe Alzheimer's disease is demonstrated by the results of a randomized, double-blind, placebo-controlled clinical study conducted in Sweden (6 month study) in patients with probable or possible Alzheimer's disease diagnosed by NINCDS-ADRDA and DSM-IV criteria, MMSE: range of 1 to 10
First-line treatment for Alzheimer's disease is donepezil hydrochloride, with doses of 10 mg/day established as effective in studies for moderate to severe Alzheimer’s disease 2.
From the Research
First-Line Treatment for Alzheimer's Disease
The first-line treatment for Alzheimer's disease is typically acetylcholinesterase inhibitors, which include donepezil, galantamine, and rivastigmine 3, 4, 5. These medications work by inhibiting the breakdown of acetylcholine, a neurotransmitter associated with memory, and have been shown to improve cognitive function, behavior, and activities of daily living in patients with mild to moderate Alzheimer's disease.
Benefits and Adverse Effects
The benefits of these medications include:
- Improved cognitive function, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 3, 6
- Improved global clinical function, as measured by the Clinician's Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+) 3, 6
- Delayed deterioration in activities of daily living (ADL) 4
- Reduced caregiver burden 4
However, these medications can also have adverse effects, including:
Comparison of Acetylcholinesterase Inhibitors
The available evidence suggests that:
- Donepezil, galantamine, and rivastigmine are all effective in improving cognitive function and global clinical function in patients with mild to moderate Alzheimer's disease 3, 6
- Galantamine may be effective in treating all aspects of Alzheimer's disease, including cognitive, functional, and behavioral symptoms 6
- Donepezil and rivastigmine may have similar efficacy, but donepezil may have a more favorable adverse effect profile 3, 7
Other Treatment Options
Other treatment options for Alzheimer's disease include:
- Memantine, an N-methyl-D-aspartate receptor antagonist, which may be used in combination with acetylcholinesterase inhibitors or as a monotherapy for moderate to severe Alzheimer's disease 5, 6
- Atypical antipsychotics, which may be used to improve behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia 5