Top Alzheimer's Disease Treatments: Latest Research

Alzheimer's disease is a progressive neurological disorder characterized by memory loss, impaired thinking skills, and difficulty performing daily tasks. It's the most common form of dementia, contributing to 60% to 70% of cases.

In Alzheimer's disease, abnormal protein deposits form in the brain, disrupting communication between brain cells and eventually causing them to die. This leads to a gradual decline in cognitive function and, eventually, to significant impairment in memory, reasoning, judgment, and other cognitive abilities.

While there's currently no cure for Alzheimer's disease, treatments are available to manage symptoms and enhance quality of life. This article aims to explore Alzheimer's disease treatment options, helping individuals living with Alzheimer's better comprehend the principles underlying these treatments and their effectiveness.

1. Cholinesterase Inhibitors

Source: Drugs.com

Many individuals with Alzheimer's have reduced levels of acetylcholine, a neurotransmitter involved in memory and learning. To address this, doctors commonly prescribe cholinesterase inhibitors like donepezil (Aricept, Adlarity), galantamine, and rivastigmine (Exelon).

These medications for Alzheimer's disease block the activity of cholinesterase, an enzyme responsible for breaking down acetylcholine in the brain. By maintaining higher acetylcholine levels, they improve neuron communication, temporarily easing symptoms such as memory loss and confusion.

Cholinesterase inhibitors are typically recommended for managing mild to moderate Alzheimer’s symptoms and are often part of a comprehensive treatment plan, which may include lifestyle adjustments, cognitive stimulation, and caregiver support.

Efficacy

A review on the efficacy of cholinesterase inhibitors found that they have limited efficacy in enhancing cognition among individuals with mild to moderate Alzheimer’s disease. However, they showed some effectiveness in improving the global state, with donepezil being identified as the most effective treatment among the class of medications.

A more recent study examined the impact of cholinesterase inhibitors on cognitive decline among a large cohort of older patients diagnosed with late-onset Alzheimer’s disease, vascular dementia, or Lewy body disease (LBD) in a real-world setting.

Their findings revealed that the Mini-Mental State Examination (MMSE) score, a measure of cognitive abilities, was significantly lower in the cholinesterase inhibitor group (5.4 points) compared to the untreated group (10.8 points), indicating a slower cognitive decline among patients receiving cholinesterase inhibitors.

This trend was particularly pronounced in patients diagnosed with late-onset Alzheimer’s disease, although similar effects were observed in vascular dementia patients. However, no significant effect on cognitive status was observed in patients with LBD.

Dosage Strength and Administration

Different forms are available for different types of cholinesterase inhibitors. For example:

• Donepezil: This drug is available in various forms, including oral film-coated tablets in strengths of 5 mg, 10 mg, and 23 mg. It is also offered as orally disintegrating tablets in 5 mg and 10 mg strengths. Additionally, transdermal patches containing donepezil are available in strengths of 5 mg and 10 mg.
• Galantamine: This is available in two main forms–immediate-release and extended-release. The extended-release capsules come in strengths of 8 mg, 16 mg, and 24 mg. The immediate-release versions are available as tablets and solutions. The solution contains 4 mg of galantamine per ml, while the tablets are offered in strengths of 4 mg, 8 mg, and 12 mg.
• Rivastigmine: This is also offered in several formulations, including oral capsules, oral liquid, and transdermal patches. The capsules come in strengths of 1.5 mg, 3 mg, 4.5 mg, and 6 mg. The oral solution contains 2.0 mg per mL. Transdermal patches are available in strengths of 4.6 mg, 9.5 mg, and 13.3 mg per 24 hours.

Side Effects

Cholinesterase inhibitors enhance the levels of acetylcholine in the body. This can lead to symptoms such as heightened motility, increased secretion, slowed heart rate, constricted pupils, diarrhea, and low blood pressure.

Initially, patients may encounter side effects such as headaches, insomnia, and minor gastrointestinal issues. However, more serious effects like dizziness, weakness, and weight loss can also arise. Additionally, prolonged muscle contraction is a possible symptom in patients using these inhibitors.

Cost

The prices of FDA-approved cholinesterase inhibitors are as follows:

• Donepezil (generic) - starts at $9.01
• Aricept (branded donepezil) - starts at $519.65
• Adlarity (branded donepezil) - starts at $463.10
• Galantamine (generic) - starts at $24.10
• Rivastigmine (generic) - starts at $74.20
• Exelon (branded rivastigmine) - starts at $700.99

The costs fluctuate depending on factors like the pharmacy, location, insurance coverage, and any available discounts or assistance programs.

2. Memantine (Namenda)

Source: Welzo

Memantine (Namenda), an N-Methyl D-Aspartate (NMDA) receptor antagonist, is thought to help with Alzheimer's disease by modulating the activity of glutamate, a neurotransmitter involved in memory and learning.

In Alzheimer's disease, glutamate excessively activates NMDA receptors, leading to neuronal damage and cognitive decline. Memantine works by blocking these NMDA receptors, thus reducing the excitotoxicity caused by glutamate and protecting neurons from damage.

Memantine is recommended for individuals experiencing moderate to severe stages of Alzheimer’s disease. Because NMDA antagonists function differently from cholinesterase inhibitors, they can be prescribed together. One such combination medication is Namzaric, which contains memantine and donepezil ER. However, it's only suitable if the patient is stable on a 10 mg dose of donepezil daily.

Efficacy

An older study investigated whether memantine alone can improve overall clinical impression and reduce dependency on caregivers compared to the placebo. The results showed that memantine was more effective than the placebo. Specifically, 73% of memantine patients had an improved clinical impression compared to 45% on the placebo.

Additionally, there was a greater improvement in dependency on caregivers among those on memantine compared to the placebo. Memantine-treated patients improved by 3.1 points, while those on placebo improved by only 1.1 points.

In a combination therapy study conducted in 2004, individuals with probable Alzheimer's disease who were already taking donepezil were randomly assigned to receive either memantine or a placebo for 24 weeks. The participants were over 50 years old and had moderate to severe cognitive impairment.

The study suggests that adding memantine to the treatment regimen of individuals already taking donepezil can provide additional benefits in terms of cognitive and functional abilities, as well as in managing behavioral symptoms associated with Alzheimer's.

Dosage Strength and Administration

Memantine is available in several dosage forms, including extended-release capsules ( in 7 mg, 14 mg, 21 mg, and 28 mg), oral solution (2 mg/mL), and tablets (5 mg and 10 mg). It’s administered with an initial starting dosage of 5 mg once daily. The target dosage is 20 mg once daily, achieved through gradual titration. The dosage is increased by 5 mg daily in weekly intervals, provided it is well tolerated by the patient.

Side Effects

The most frequently reported side effects of memantine in clinical trials are dizziness, headache, confusion, diarrhea, and constipation. Other side effects include fatigue, pain, high blood pressure, weight gain, hallucinations, aggressive behavior, vomiting, abdominal pain, and urinary incontinence.

Cost

The cost of memantine in the US varies based on the dosage form and pharmacy. For generic memantine, a 30-day supply of 10 mg tablets typically costs around $14.08 to $96.99, while its branded version, Namenda, comes at $434.23 to $499.35 for the same quantity. On the other hand, Namzaric (memantine/donepezil ER) costs $580.59.

3. Lecanemab (Leqembi)

A new treatment for Alzheimer's disease, lecanemab (Leqembi), was approved by the FDA in 2023 using the Accelerated Approval pathway.

This new medication for Alzheimer's disease targets the underlying pathology of the condition. It is an anti-amyloid beta (Aβ) monoclonal antibody formulated to reduce amyloid plaques in the brain, which are believed to play a key role in the development and progression of Alzheimer's disease.

Efficacy

Lecanemab’s approval was based on the results of a Phase 3 randomized, controlled clinical trial. The research involved 1795 individuals aged 50 to 90 with early Alzheimer's disease, evidenced by mild cognitive impairment or mild dementia and confirmed amyloid accumulation. Results after 18 months indicated that the lecanemab group exhibited a smaller increase in CDR-SB score (1.21) than the placebo group (1.66), indicating less cognitive decline.

Furthermore, a substudy of 698 participants showed significantly reduced brain amyloid plaques with lecanemab. Overall, lecanemab demonstrated efficacy in reducing amyloid markers and slowing cognitive and functional decline in early Alzheimer's disease, albeit with certain adverse effects. More research is needed to ensure it's safe and effective in the long run.

Dosage Strength and Administration

The treatment is given intravenously every two weeks, with each infusion lasting approximately one hour. These infusions are generally performed at hospitals or infusion therapy centers.

Side Effects

In lecanemab’s phase 3 trial, the most common adverse events were infusion-related reactions, occurring in 26.4% of participants compared to 7.4% in the placebo group. These reactions were usually mild to moderate and typically occurred with the first dose, including symptoms like fever, chills, itching, rash, nausea, and changes in blood pressure.

Amyloid-related imaging abnormalities (ARIA) were also observed. Other common side effects included headaches and falls. Less common serious adverse events included atrial fibrillation, syncope, and angina pectoris.

Cost

The estimated per-patient-per-year value of Leqembi in the US is $37,600. However, Eisai, the manufacturer of Leqembi, has decided to price the drug at a wholesale acquisition cost (WAC) of $26,500 per year to promote broader patient access, reduce the overall financial burden, and support health system sustainability.

This price is based on a 10mg/kg IV biweekly dosage for an average US patient weight of 75kg. The WAC for the 200mg vial is $254.81, and for the 500mg vial, it is $637.02. Actual annual pricing may vary by patient. Additionally, Eisai is pursuing a less frequent maintenance dosing regimen, such as monthly instead of biweekly, after significant amyloid beta clearance. This could potentially reduce the annual cost of Leqembi during the maintenance phase to about half of the current price.

Takeaway

Alzheimer's disease medications are evolving, offering ways to manage symptoms and potentially slow progression. Commonly prescribed medications include cholinesterase inhibitors like donepezil, galantamine, and rivastigmine, which help maintain acetylcholine levels in the brain.

Memantine, an NMDA receptor antagonist, protects neurons by modulating glutamate activity and can be used alone or with AChEIs for additional symptom management.

The FDA's recent approval of Leqembi, an anti-amyloid beta monoclonal antibody, offers a promising new treatment by targeting amyloid plaques and slowing cognitive decline in early Alzheimer's, though further research on its long-term safety and effectiveness is needed.

Choosing Alzheimer's medication involves considering efficacy, side effects, dosage, and cost, tailored to individual patient needs. As research progresses and new treatments emerge, the goal remains to enhance the quality of life and strive for better outcomes.

FAQs on Alzheimer's Disease Treatment

What are the symptoms of Alzheimer’s disease?

Alzheimer's symptoms can vary, but memory problems are usually one of the first signs. Early symptoms also include difficulty finding words, trouble understanding visual image, and impaired reasoning or judgment. As the disease progresses, symptoms worsen, including increased confusion and behavioral changes.

What are the risk factors of Alzheimer’s disease?

Age is the most significant risk factor for Alzheimer's disease. The majority of individuals with Alzheimer's are diagnosed at age 65 or older, with fewer than 10% of cases occurring before this age. The risk of developing Alzheimer's increases with advancing age, approximately one in 13 individuals aged 65 to 84 and one in three individuals aged 85 and older are affected. Additional key risk factors include family history, lifestyle choices, existing medical conditions, and genetic markers (presence of the apolipoprotein E APOE gene).

Can lifestyle changes reduce the risk of Alzheimer's disease?

Yes. These include managing high blood pressure, controlling blood sugar, maintaining a healthy weight through balanced eating and regular exercise, quitting smoking, moderate alcohol consumption, preventing and correcting hearing loss, and ensuring adequate sleep.

Are there Alzheimer's disease treatment guidelines for patients and families to consider when choosing a treatment plan?

Yes, there are Alzheimer's disease treatment guidelines for patients and families to consider when choosing a treatment plan. These guidelines help navigate the complexities of managing the disease and ensuring the best possible care. Key considerations include diagnosis and assessment, medication options, non-pharmacological interventions, lifestyle modification, support for caregivers, advanced planning, regular communication with healthcare providers, and personalized care.

Is genetic testing available for Alzheimer's disease?

Genetic tests aren't typically used in clinics for diagnosing or predicting Alzheimer's risk. However, if someone exhibits early symptoms and has a strong family history, a specialist might order tests for APP, PSEN1, and PSEN2. APOE testing, while available, doesn't definitively predict Alzheimer's development. It's mainly utilized in research to identify participants with elevated risk, aiding in early brain change detection and treatment comparison.