Chapter 30: Alzheimer Disease

Content Update

March 25, 2025

Donanemab-azbt (Kisunla™): Newly FDA Approved Amyloid Beta-Directed Antibody for the Treatment of Alzheimer’s Disease: Donanemab (Kisunla™) was recently FDA-approved for the treatment of Alzheimer’s disease in patients with mild cognitive impairment or mild dementia.¹ Targeting insoluble N-truncated pyroglutamate amyloid beta, donanemab binds to amyloid beta plaques in the brain with the goal of destroying plaques and slowing disease progression.² Recent clinical trials have shown promising data; however, the risks of treatment and costliness of therapy remain significant limitations. In the phase 3, randomized, double-blind, placebo-controlled trial, TRAILBLAZER-ALZ 2, donanemab showed significant improvement in the integrated Alzheimer’s Disease Rating Scale (iADRS), representing a slowing of disease progression. In comparison to the only other commercially available monoclonal antibody, lecanemab, donanemab offers a different mechanism for targeting disease progression, focusing on already existing amyloid plaques versus those in the process of forming. Additional studies of donanemab and head-to-head comparisons involving both monoclonal antibodies are necessary to provide more insight into efficacy and safety of these medications in the treatment of Alzheimer’s disease.

Content Update

December 21, 2023

Lecanemab-irmb (LEQEMBI®): The first FDA-approved monoclonal antibody for Alzheimer's Disease: Lecanemab-irmb (LEQEMBI®), a humanized IgG1 monoclonal antibody, has been considered as a potential treatment for Alzheimer's disease. It aims to target aggregated soluble and insoluble forms of amyloid beta, which are elemental to the disease pathophysiology. In a Phase III trial, lecanemab showed promise in reducing Clinical Dementia Rating scores, amyloid burden on positron-emission tomography scans, and cognitive impairment and functional scores compared to placebo. Further study is warranted to ensure its safety for the target population, as participants receiving lecanemab experienced more adverse events. This antibody represents a potential advancement in Alzheimer's therapy, pending comprehensive safety evaluation.

Content Update

August 01, 2023

Donepezil Transdermal System (Adlarity®): The First Once-Weekly Patch Approved for Treatment of Mild, Moderate, and Severe Alzheimer’s Dementia: Donepezil (Adlarity®) is the second transdermal system (TDS) approved in the U.S. for treatment of Alzheimer’s dementia of mild, moderate, and severe types in adults. In comparison to the donepezil oral formulation, the donepezil TDS had shown overall clinical benefit in cognition in Alzheimer’s dementia patients with less incidence of adverse events aside from application site reactions. With less frequent administration and improved pharmacokinetics, this donepezil formulation provides easier adherence for patients who are unable to tolerate the oral formulation known for gastrointestinal events.

LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

1. Describe the epidemiology of Alzheimer disease (AD) and its effects on society.

2. Describe the pathophysiology, including genetic and environmental factors that may be associated with AD.

3. Detail the clinical presentation of the typical patient with AD.

4. Describe the clinical course of the disease and typical patient outcomes.

5. Explain how nonpharmacologic therapy is ...