Current Approaches for the Treatment of Alzheimer's Disease

Alzheimer’s disease is a complex and debilitating condition that, until recently, had no FDA-approved treatments that go beyond symptom management to slow or halt its progression. Eisai’s lecanemab (Leqembi) is the second FDA-approved treatment for Alzheimer’s disease to enter the market since 2003, sparking immense hope for neurologists and patients alike in the fight against Alzheimer’s disease.

In addition to the first generation of disease-modifying therapies, there are several drugs, therapies, and lifestyle interventions that can be used to manage the symptoms of Alzheimer’s disease.

In this article, we will walk you through the current approaches for the treatment of Alzheimer’s disease, including:

• Disease-modifying therapies
• Drugs to manage cognitive symptoms
• Drugs to manage behavioral changes
• Adjunct therapies and lifestyle interventions

Disease-Modifying Therapies

Historically, treatment of Alzheimer’s disease was centered around alleviating the symptoms that result from the pathological changes in the brain and, consequently, the loss of neurons in various brain regions. However, a new class of therapies, known as monoclonal antibody therapies, aims to modify the disease course. 

In 2021, Aducanumab received accelerated approval from the FDA for the treatment of Alzheimer’s disease, marking the first FDA-approved drug in the monoclonal antibody therapy class. Lecanemab, the second FDA-approved drug in this class, also addresses the underlying pathology of Alzheimer’s disease by targeting and reducing beta-amyloid plaques early in the initial stages of the disease.

Clinical trial data released on November 29, 2022, demonstrated lecanemab was effective in reducing beta-amyloid plaques and slowing cognitive decline for some patients. On January 6, 2023, lecanemab received accelerated approval from the FDA for Alzheimer’s disease treatment. Compared to aducanumab, lecanemab was found to have a higher safety profile and to bind more strongly to beta-amyloid protofibrils, representing a key milestone in the fight against Alzheimer’s disease.

On April 7, 2022, the Centers for Medicare and Medicaid (CMS) released a national policy coverage for aducanumab as well as any future monoclonal antibodies directed against beta-amyloid approved by the FDA for the treatment of Alzheimer’s disease. Because lecanemab was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. 

Drugs to Manage Cognitive Symptoms

Addressing the cognitive symptoms of Alzheimer’s disease can help preserve a person’s independence and maintain quality of life. There are several FDA-approved prescription drugs that may be used to manage cognitive symptoms in people living with Alzheimer’s disease. 

In the mild to moderate stages of Alzheimer’s disease, cholinesterase inhibitors are commonly prescribed to treat cognitive symptoms, such as issues with memory, language, thinking, and judgment. In the moderate to severe stages of Alzheimer’s disease, glutamate regulators are often prescribed to decrease symptoms and improve cognitive functions such as memory, language, reason, and attention.

Cholinesterase inhibitors work by preventing the breakdown of acetylcholine (a neurotransmitter important for learning and memory). Glutamate regulators work by regulating the activation of glutamate (a neurotransmitter important for synaptic plasticity and survival of neurons) and blocking the toxic effects of excessive glutamate. Cholinesterase inhibitors and glutamate regulators can also be used in combination in some cases (Namzaric^Ⓡ).

Drugs to Manage Behavioral Changes

For many friends, families, and caregivers, behavioral changes can be the most distressing and difficult parts of caring for someone living with Alzheimer’s disease. As the disease progresses and regions of the brain, such as the frontal lobe, become damaged, people living with Alzheimer’s disease often experience non-cognitive symptoms, such as irritability, anxiety, depression, hallucinations, delusions, and disturbed sleep.

Non-drug interventions are often the first line of defense for behavioral changes. However, there are several medications that may be prescribed when appropriate.

Note: Most of the examples above represent “off-label” drug use, which is when an FDA-approved medication is prescribed for a different condition than the one it was originally approved for. For example, while citalopram is FDA-approved specifically to treat depression (not Alzheimer’s), it may be used to manage depression in those living with Alzheimer’s disease.

Treatment of Alzheimer’s Disease: Therapies and Lifestyle Interventions

In addition to medications, treatment of Alzheimer’s disease may involve adjunct therapies, such as those detailed below:

• Cognitive Stimulation Therapy (CST): CST is a short-term, evidence-based intervention program for patients with mild to moderate Alzheimer’s disease (or mild to moderate dementia due to other causes). CST involves a series of themed activities designed to actively stimulate and engage patients socially and mentally. 
• Reminiscence Therapy: Reminiscence therapy integrates the use of the five senses—sight, touch, taste, smell, and sound—to help Alzheimer’s patients recall specific positive memories. The overarching school of thought for this approach lies in the idea that if a patient engages in activities that evoke memories, it may wake up certain neural connections and reactivate dead parts—like jumper cables for the brain.
• Occupational Therapy: Occupational therapy helps Alzheimer’s and dementia patients maintain their quality of life and remain as independent as possible through specific intervention strategies. Types of occupational therapy include health promotion, remediation, maintenance, and modification.

Effective treatment and management of Alzheimer’s disease require a well-rounded approach. Lifestyle interventions often play an essential role in preserving the overall health and well-being of Alzheimer’s patients and can help manage behavioral and psychological symptoms. Lifestyle interventions may include routine exercise, weight management, diet and nutrition, social and mental stimulation, stress reduction, and sleep hygiene.

Monitoring the Effects of Treatment in Alzheimer’s Patients

Regardless of the drugs, therapies, or lifestyle interventions involved in a patient’s treatment and management plan, healthcare providers and caregivers should consider monitoring the neurocognitive effects of treatment. Routine neurocognitive assessments can not only provide insight into how well the treatment plan is working but can also further inform care needs and identify patients who may be at risk of falls to prevent serious injury.

To learn more about how Alzheimer’s disease is treated, listen to this podcast sponsored by Altoida: Treatment for Alzheimer’s Disease (Part 2): Medication and Rehabilitation Therapies.