What is Alzheimer's disease (AD)?

From the Guidelines

Alzheimer's disease is a progressive neurological disorder that requires early diagnosis and treatment to improve quality of life, and the most recent guidelines recommend a high-quality, evidence-supported evaluation process for diagnostic evaluation, testing, counseling, and disclosure of suspected Alzheimer's disease and related disorders. According to the Alzheimer's Association clinical practice guideline 1, a comprehensive evaluation process is essential to characterize, diagnose, and disclose the patient's cognitive functional status, cognitive–behavioral syndrome, and likely underlying brain disease. The guideline recommends that clinicians use a combination of clinical tests, including cognitive and behavioral assessments, laboratory tests, and imaging studies, to diagnose Alzheimer's disease and related disorders.

The disease involves accumulation of amyloid plaques and tau tangles in the brain, leading to neuron death and brain atrophy, and risk factors include age, family history, and genetics, with the APOE-e4 gene increasing risk significantly 1. While there is no cure, medications like cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine can temporarily improve symptoms or slow progression. Typical treatment involves donepezil starting at 5mg daily, potentially increasing to 10mg after 4-6 weeks. Newer treatments like aducanumab (Aduhelm) target amyloid plaques in the brain but have limited availability and effectiveness 1. Non-drug approaches include maintaining mental activity, regular exercise, healthy diet, quality sleep, and social engagement.

Some key points to consider in the diagnosis and treatment of Alzheimer's disease include:

• Early symptoms include forgetting recent conversations or events, which gradually worsen to include severe memory impairment, confusion, and inability to perform daily tasks
• A comprehensive evaluation process is essential to characterize, diagnose, and disclose the patient's cognitive functional status, cognitive–behavioral syndrome, and likely underlying brain disease
• Clinicians should use a combination of clinical tests, including cognitive and behavioral assessments, laboratory tests, and imaging studies, to diagnose Alzheimer's disease and related disorders
• Medications like cholinesterase inhibitors and memantine can temporarily improve symptoms or slow progression, and newer treatments like aducanumab target amyloid plaques in the brain
• Non-drug approaches, such as maintaining mental activity, regular exercise, healthy diet, quality sleep, and social engagement, are also important for improving quality of life.

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 This study showed that patients on donepezil hydrochloride experienced significant improvement on both measures compared to placebo. The ability of donepezil hydrochloride to improve cognitive performance was assessed with the Severe Impairment Battery (SIB). Donepezil hydrochloride treatment was statistically significantly superior to placebo.

Donepezil hydrochloride is effective in the treatment of moderate to severe Alzheimer's disease.

• The drug has been shown to improve cognitive performance and daily function in patients with severe Alzheimer's disease.
• Statistically significant differences were observed between donepezil hydrochloride and placebo on measures of cognitive performance and daily function. 2

From the Research

Alzheimer's Disease Treatment

• The current recommended standard of care for the symptomatic treatment of mild to moderate Alzheimer's disease is cholinesterase inhibitors 3.
• Cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, have demonstrated efficacy in improving cognition, function, and behavior in patients with Alzheimer's disease 3, 4.
• However, the benefits of cholinesterase inhibitors are not sustained indefinitely, and the illness continues to progress even while patients are receiving treatment 3.

Cholinesterase Inhibitors

• Donepezil, galantamine, and rivastigmine are the most commonly used cholinesterase inhibitors for the treatment of Alzheimer's disease 4, 5.
• These drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory 5.
• The efficacy of these drugs appears to be comparable, with improvements in cognitive function, activities of daily living, and behavioral disturbances 5.

Safety and Tolerability

• Cholinesterase inhibitors are generally well-tolerated, but can cause peripheral cholinergic adverse effects, such as nausea, vomiting, and diarrhea 4, 5.
• Donepezil may have fewer adverse effects compared to rivastigmine 5.
• Memantine, another pharmacotherapeutic option for Alzheimer's disease, improves cognitive functions and behavioral disturbances, and is well-tolerated, with a safety profile comparable to that of the placebo 6.

Treatment Recommendations

• The selection of the best course of treatment for Alzheimer's disease should be based on evidence gathered by systematic reviews and meta-analyses of randomized controlled trials 6.
• Combined treatment with memantine and donepezil may be the most useful treatment for Alzheimer's disease 6.
• Patients should be regularly monitored for potential serious side effects of cholinesterase inhibitor therapy, and attempts to cautiously discontinue all medications not necessary for quality of life should be made at the terminal stages of the disease 7.