Advances in Alzheimer Disease Treatment: A Transformative Time for Pharmacists

Alzheimer disease (AD) is one of the most daunting neurodegenerative disorders, affecting more than 6 million Americans, most of whom are 65 years or older. The disease advances in stages, starting with mild cognitive impairment and progressing to severe dementia. AD is characterized by the buildup of β-amyloid plaques and tau protein tangles, which together drive neurodegeneration. β-amyloid, a protein usually cleared from the brain, accumulates abnormally in AD and forms plaques between neurons. These plaques interfere with synaptic signaling and can trigger inflammatory responses. At the same time, tau proteins inside neurons become hyperphosphorylated, causing them to detach from microtubules and aggregate into tangles. This disrupts the transport of essential nutrients and organelles within the cell, ultimately leading to neuronal dysfunction and death. The combined impact of plaques and tangles leads to widespread brain atrophy and the progressive cognitive and functional decline seen in AD.¹

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Although some plaque and tangle buildup occurs with normal aging, it is significantly greater and more widespread in individuals with AD, particularly in regions of the brain critical for memory. Early symptoms typically include trouble remembering new information and gradually worsen to confusion, mood swings, and difficulties with speech and movement. AD treatments primarily focus on reducing β-amyloid plaques by promoting their removal or preventing their formation. They also target tau protein to inhibit its abnormal aggregation and spread, thereby addressing the core pathological processes driving the disease.²

Although symptomatic therapies such as cholinesterase inhibitors and memantine have been mainstays for decades, recent years have ushered in a new wave of disease-modifying treatments (DMTs) that target the underlying pathology of AD. These developments are reshaping the clinical landscape, and pharmacists are uniquely positioned to support safe, effective, and personalized treatment.

Advances in Anti-Amyloid Antibody Treatment

Two monoclonal antibodies, lecanemab (Leqembi; Eisai Inc/Biogen) and donanemab (Kisunla; Eli Lilly and Co), have garnered significant attention as the first DMTs for early-stage AD.

Lecanemab targets soluble β-amyloid protofibrils and received full FDA approval in July 2023 for mild cognitive impairment or mild dementia due to AD.^3,4 Data from the Clarity AD trial (NCT03887455) demonstrated that lecanemab reduced β-amyloid levels and slowed cognitive and functional decline over 18 months vs placebo. However, adverse events occurred, and longer studies are needed to confirm its long-term safety and effectiveness.⁵

Donanemab targets deposited β-amyloid plaques and was approved by the FDA in July 2024. The TRAILBLAZER-ALZ 2 study (NCT04437511) demonstrated that donanemab significantly slowed disease progression at 76 weeks in patients with early AD with low to medium tau levels and in the combined tau pathology population.⁶

Both these anti-amyloid therapies are given by intravenous (IV) infusion every few weeks and carry a risk of amyloid-related imaging abnormalities, which are MRI-detected brain changes such as fluid accumulation or microhemorrhages that require monitoring.^7,8 Regular MRI scans are required before and during treatment to monitor for these potential adverse effects. Notably, the ongoing need for imaging and infusion visits creates logistical challenges for patients.

Advancing Administration: The Shift Toward Subcutaneous Formulations

To enhance patient access and ease of treatment, subcutaneous (SC) formulations of anti-amyloid therapies are currently under development. Early clinical data indicate these SC options may offer comparable effectiveness to IV infusions while reducing infusion-related reactions.⁹ By enabling administration in outpatient settings or even at home, these formulations could improve patient convenience, reduce health care resource utilization, and potentially increase adherence. Pharmacists will play a critical role in educating patients and caregivers on proper injection techniques, monitoring for adverse effects, and supporting treatment continuity as these therapies become available.

Optimizing Symptom Relief: Benzgalantamine's Role in Alzheimer Therapy

Benzgalantamine (Zunveyl; Alpha Cognition, Inc) is a prodrug of galantamine formulated to bypass the stomach by delaying its conversion to the active drug until it reaches the intestines. This approach reduces exposure of the stomach lining to the active compound, thereby lowering the incidence of gastrointestinal adverse effects such as nausea and vomiting that are common with traditional cholinesterase inhibitors. It ultimately enhances patient tolerability and adherence.¹⁰ It offers similar symptomatic benefits while improving tolerability in patients with mild to moderate AD.

In clinical studies, benzgalantamine has demonstrated symptomatic benefits comparable to those of conventional galantamine, including improvements in cognitive function, attention, and activities of daily living in adults with mild to moderate AD. Its favorable tolerability profile is particularly important for older adults, who are often sensitive to gastrointestinal upset and polypharmacy complications.¹¹ By combining established cognitive benefits with improved safety and patient comfort, benzgalantamine represents a meaningful advance in optimizing cholinergic therapy for AD.

In clinical studies, benzgalantamine has demonstrated symptomatic benefits comparable to those of conventional galantamine, including improvements in cognitive function, attention, and activities of daily living in adults with mild to moderate AD. Its favorable tolerability profile is particularly important for older adults, who are often sensitive to gastrointestinal upset and polypharmacy complications.¹¹ By combining established cognitive benefits with improved safety and patient comfort, benzgalantamine represents a meaningful advance in optimizing cholinergic therapy for AD.

Advancing Diagnosis: The Impact of Blood-Based Biomarkers

In May 2025, the FDA approved the Lumipulse G pTau217/β-Amyloid 1-42 Plasma Ratio test (Fujirebio Diagnostics, Inc) for the early detection of β-amyloid plaques associated with AD in adults aged 55 and older who show signs or symptoms of cognitive decline.¹² This blood-based test offers a less invasive alternative to PET imaging or lumbar puncture, supporting earlier diagnosis and treatment planning.

In a validation study involving 499 cognitively impaired adults, test results were compared against amyloid PET imaging or cerebrospinal fluid biomarkers. Positive plasma ratio findings were confirmed in approximately 91.7% to 92% of cases, whereas negative results aligned with the confirmed absence of amyloid pathology in approximately 97% to 97.3% of participants. Indeterminate (borderline) results occurred in less than 20% of cases, reflecting high overall diagnostic reliability.¹²

Advancing AD Treatment Through Precision Medicine

AD care is moving toward precision medicine, in which treatment decisions are guided by a patient’s specific biomarkers, such as amyloid and tau levels, and genetic factors, such as the APOE genotype. This personalized approach helps identify which patients are most likely to benefit from specific therapies or experience adverse effects. Pharmacists must stay current with these innovations, understanding their mechanisms and facilitating their safe integration into patient care.

Conclusion

The landscape of AD management is undergoing a profound transformation, with innovations spanning DMTs, improved symptomatic options, and accessible diagnostic tools. Antiamyloid antibodies such as lecanemab and donanemab, along with their emerging SC formulations, are enabling clinicians to intervene earlier in the disease course while balancing efficacy with safety monitoring. Meanwhile, therapies such as benzgalantamine offer meaningful advances in symptom relief, enhancing tolerability and supporting patient adherence. The approval of blood-based biomarker tests further empowers clinicians to detect disease earlier, stratify risk, and initiate treatment strategies more confidently.

For pharmacists, these advancements underscore a shift toward a more active and collaborative role in AD care. Pharmacists are uniquely positioned to educate patients and caregivers, monitor for adverse events, ensure adherence, and guide the appropriate use of complex therapies informed by biomarker results. As precision medicine becomes central to AD treatment, pharmacy professionals will serve as essential partners in translating cutting-edge science into practical, patient-centered care—helping optimize outcomes during a pivotal new era in AD management.

REFERENCES

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2. What is Alzheimer’s disease? Alzheimer’s Association. Accessed July 31, 2025. https://www.alz.org/alzheimers-dementia/what-is-alzheimers

3. Lecanemab approved for treatment of early Alzheimer’s disease. Alzheimer’s Association. Accessed July 31, 2025. https://www.alz.org/alzheimers-dementia/treatments/lecanemab-leqembi

4. Donanemab approved for treatment of early Alzheimer’s disease. Alzheimer’s Association. Accessed July 31, 2025. https://www.alz.org/alzheimers-dementia/treatments/donanemab

5. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948

6. Sims JR, Zimmer JA, Evans CD, et al; TRAILBLAZER-ALZ 2 Investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527. doi:10.1001/jama.2023.13239

7. Leqembi. Prescribing information. Eisai Inc; 2023. Accessed July 31, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s001lbl.pdf

8. Kisunla. Prescribing information. Eli Lilly & Co; 2024. Accessed July 31, 2025. https://uspl.lilly.com/kisunla/kisunla.html#pi

9. Bugos C. Injectable Alzheimer’s drugs could save patients trips to the hospital. VeryWell Health. January 21, 2025. Accessed July 31, 2025. https://www.verywellhealth.com/injectable-alzheimers-drugs-8776312

10. Zunveyl. Prescribing information. Alpha Cognition Inc; 2024. Accessed July 31, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218549s000lbl.pdf

11. Alpha Cognition’s oral therapy Zunveyl receives FDA approval to treat Alzheimer’s disease. News release. Alpha Cognition. July 29, 2024. Accessed July 31, 2025. https://www.alphacognition.com/investors/news/alpha-cognitions-oral-therapy-zunveyl-receives-fda-approval-to-treat-alzheimers-disease-

12. FDA clears first blood test used in diagnosing Alzheimer’s disease. News release. FDA. May 16, 2025. Accessed July 31, 2025. https://www.fda.gov/news-events/press-announcements/fda-clears-first-blood-test-used-diagnosing-alzheimers-disease