Treatment Advances for Alzheimer Disease Provide Hope

Alzheimer disease (AD) is a progressive brain disorder that destroys memory and thinking skills, with symptoms typically presenting later in life. An estimated 6 million individuals in the US are affected by AD, most of whom are at least 65 years old. AD is the seventh leading cause of death in the US.¹

Changes to the brain may occur 10 or more years before symptoms present. Mild AD is marked by memory loss and other cognitive complications, such as a wandering train of thought, repeating of questions, and behavior changes. In moderate AD, damage occurs to the areas of the brain that control language, reasoning, conscious thought, and sensory processing. Ultimately, progression to severe AD results in changes throughout the brain and brain shrinkage. At this point, memory loss and confusion worsen, and the ability to communicate and care for oneself is severely compromised.¹

Although there is no cure for AD, there are treatments that may delay progression and other treatments to alleviate symptoms. New treatments are slowing the progression of the disease and improving symptom management, representing significant steps forward for patients and caretakers.

SLOWING PROGRESSION

New drugs are able to slow the progression of AD by undermining the biology of the disease process. For example, antiamyloid agents remove amyloid-ß, a protein that accumulates into plaques in the brain. Each of these treatments works differently and targets amyloid-ß at different stages of plaque formation. These treatments slow the progression of AD in patients with early-stage AD, allowing the patient more time to participate in daily life. However, these treatments do have adverse effects, including amyloid-related imaging abnormalities (ARIAs). As a common adverse effect, ARIAs do not typically have symptoms but can be serious.²

The antiamyloid treatments currently available are donanemab-azbt (Kisunla; Eli Lilly) and lecanemab-irmb (Leqembi; Eisai, Biogen). Donanemab-azbt is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed at amyloid-ß. It is administered by intravenous infusion over a period of 30 minutes once every 4 weeks and was FDA approved on July 2, 2024.³ In the TRAILBLAZER-ALZ 2 (NCT04437511) study, investigators found that the treatment significantly slowed clinical progression at 76 weeks, with 23 of 24 evaluated outcomes being statistically significant.⁴

Lecanemab-irmb is a humanized IgG1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid-ß. This is administered by intravenous infusion over a period of 1 hour every 2 weeks and was FDA approved on July 6, 2023.⁵

In the CLARITY AD (NCT03887455) trial, investigators are evaluating the efficacy of lecanemab-irmb in 856 individuals with AD who had mild cognitive impairment or mild dementia and confirmed presence of amyloid-ß pathology. Patients who received lecanemabirmb had a statistically significant dose- and time-dependent reductions of amyloid-ß plaque.⁶

TREATING SYMPTOMS

Cholinesterase inhibitors such as donepezil (Aricept; Eisai), rivastigmine, and galantamine (Razadyne; Janssen) are indicated for mild to moderate AD. These medications decrease the breakdown of acetylcholine and support communication between nerve cells.² Memantine (Namenda; Allergan) is a glutamine regulator approved for moderate to severe AD. It regulates glutamine and may improve memory, attention, reasoning, language, and the ability to perform simple tasks. Additionally, the combination of donepezil and memantine (Namzaric; AbbVie) is a cholinesterase inhibitor and glutamine regulator indicated for the treatment of moderate to severe AD.²

Noncognitive symptoms, those that affect behavior and personality, can equally impact a person’s quality of life. These symptoms can manifest as sleep disturbances, agitation, hallucinations, and delusions, but there are pharmacological treatments that may help. For instance, suvorexant (Belsomra; Merck) is an orexin receptor antagonist prescribed for insomnia in patients with mild to moderate AD. It works by inhibiting orexin, a neurotransmitter involved in the sleep-wake cycle. Brexpiprazole (Rexulti; Otsuka, Lundbeck) is an atypical antipsychotic approved for the treatment of agitation associated with dementia. However, it is not approved for dementia related psychosis without agitation.²

There are many nonpharmacological treatments for AD, including the following^7-10:

• A brain-healthy lifestyle can help counter dementia symptoms. This includes being physically and socially active, eating well, managing stress, and challenging the brain.
• Cognitive behavioral therapy can help with adjustment to the diagnosis, depression, and future planning.
• Music therapy can help with communication, coordination, expression, and socialization.
• Activities such as memory and orientation exercises, art therapy, aromatherapy, and contact with animals can help delay mental ability loss.
• Nutritional interventions can help with cognition and function.
• Environmental modifications can encourage creative solutions to dementia symptoms.
• Caregiver training for family members can help as they adjust to the diagnosis and learn how to help their family member.

A study by Brown University found that nondrug interventions for AD are effective and cost-effective. They can improve quality of life and reduce nursing home admissions, and are not associated with adverse events.¹¹

ON THE HORIZON

AD research is focused on developing new treatments to slow or stop the progression of the disease. Areas of focus for this research include reducing the chronic inflammation in the brain caused by AD, the role of insulin in the brain and how changes in insulin may be related to AD, and investigating the role of gut health in AD, including whether probiotics, prebiotics, and dietary interventions can help.¹²

Researchers are also developing new drug delivery systems, such as nanoparticle-based systems and focused ultrasound technology to better administer novel treatments. Finally, as in many other disease states, investigators are recognizing the importance of personalized treatment plans to address patients’ individual needs and challenges.¹²

PHARMACISTS’ ROLE

Pharmacists play a critical role in the care of patients with AD and their caregivers. Because of their close relationships and frequent interactions with patients, pharmacists may notice changes in behavior, memory, or mood, and can also monitor patients with known predisposing conditions, such as cardiovascular disease, diabetes, hypertension, hypercholesterolemia, hearing loss, and depression.

As medication experts, pharmacists can determine whether certain treatments are negatively impacting cognition and can review patient records to identify potential risks before symptoms appear. Pharmacists are also crucial educators for patients and caregivers, providing information about treatments, adverse effects, and medication adherence.

Pharmacists can work with the larger health care team to fine-tune medication plans, ensuring correct dosages and monitoring patients to interactions. Patients should also be informed about lifestyle adjustments that may reduce the risk of AD, such as dietary changes, exercise, and cognitive activities. Finally, pharmacists can provide resources available in their area for patients with AD and their caregivers. The Table highlights some available resources.