ST. LOUIS — For decades, researchers have been on a quest to find effective treatments for Alzheimer’s disease, a devastating neurodegenerative condition that impairs memory, thinking, and the ability to perform daily activities. The recent approval of new medications provides a glimmer of hope, but lingering questions remain regarding the tangible benefits these treatments offer to patients and their families.
A new study from the Washington University School of Medicine sheds light on this crucial question, emphasizing what truly matters to patients and their families: maintaining independence in everyday life. In pharmaceutical trials for new Alzheimer’s treatments, success is often measured using clinical scales that may not accurately reflect real-world benefits. One such scale is the Clinical Dementia Rating Sum of Boxes (CDR-SB), which is frequently utilized in clinical trials. However, the relevance of small improvements on this scale for patients and their families remains unclear. Does a slight enhancement in scores equate to more time spent living independently, managing finances, driving, or preparing meals?
Driven by these pressing questions, researchers conducted a comprehensive analysis to explore how scores on clinical tests correlate with practical outcomes that patients and families value. Their findings, published in the peer-reviewed journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, provide a fresh framework for understanding the benefits of Alzheimer’s treatments. “What we aimed to achieve was to provide patients with meaningful information that would assist them in making informed decisions about their care,” stated Dr. Sarah Hartz, Ph.D., a senior author and professor of psychiatry at WashU Medicine. “Patients want to know how long they can live independently, rather than abstract metrics like percent change in decline.”
The study highlighted two recently approved medications, lecanemab and donanemab, which could potentially extend independence in daily activities by approximately 10 months for patients in the early stages of Alzheimer’s disease. This finding transforms abstract clinical trial results into concrete benefits that patients and families can grasp when making treatment decisions.
As Alzheimer’s disease progresses, it leads to a decline in memory and thinking, ultimately affecting the ability to perform everyday tasks. Many families prioritize maintaining independence for as long as possible, enabling loved ones to continue living at home, managing their own affairs, and preserving dignity and quality of life.
The focus of the study was on individuals with early onset of Alzheimer’s disease who are eligible for the new anti-amyloid treatments. These medications target and eliminate amyloid plaques in the brain, a hallmark of Alzheimer’s disease. Lecanemab was approved in July 2023, followed by donanemab in July 2024, both demonstrating modest but statistically significant effects in slowing disease progression in clinical trials. However, the clinical significance of these treatments remains a subject of debate, with experts questioning whether the minor improvements on clinical scales are worth the costs, potential side effects, and the burden of regular intravenous infusions.
Patients and their families face challenging decisions when considering these new treatments. As the study authors highlight, they must determine whether to undergo a treatment that may not lead to improvement or even halt disease progression. At best, these treatments might only slow the decline. The treatment regimen involves biweekly or monthly infusions and carries certain risks that need careful consideration. Dr. Suzanne Schindler, Ph.D., a co-author and WashU Medicine physician who treats individuals with Alzheimer’s disease, notes, “My patients often ask, ‘How long can I drive? How long will I be able to manage personal hygiene? How much extra time would this treatment provide me?’”
The Washington University researchers aimed to bridge the gap between clinical trial measurements and real-world outcomes. They questioned how CDR-SB scores relate to independence in daily activities and how much additional independence these new treatments might provide. The research team analyzed data from 282 participants from the Knight Alzheimer Disease Research Center who had either very mild or mild Alzheimer’s disease with confirmed amyloid pathology. The participants were monitored for an average of 2.9 years, allowing researchers to assess cognitive abilities and functional independence regularly.
The study examined two types of daily activities: instrumental activities of daily living (IADLs), which include managing finances, driving, remembering medications, and preparing meals, and basic activities of daily living (BADLs), which entail fundamental self-care tasks like bathing, dressing, and grooming. By analyzing the relationship between CDR-SB scores and independence over time, the researchers identified critical thresholds. They found that loss of independence in IADLs typically occurred when a person’s CDR-SB score exceeded 4.5, while loss of independence in basic self-care activities occurred at a higher score of over 11.5.
Using data from clinical trials of lecanemab and donanemab, researchers estimated how much these treatments might delay reaching critical thresholds for independence. For someone with early Alzheimer’s disease (baseline CDR-SB score of 2), treatment with lecanemab could potentially extend independence in IADLs by approximately 10 months. In comparison, donanemab treatment for individuals with low or medium levels of tau protein (another Alzheimer’s biomarker) might extend independence by around 13 months. The researchers provided specific estimates for patients at varying stages of the disease. A typical individual with very mild symptoms could expect to maintain independence for an additional 29 months without treatment, compared to 39 months with lecanemab and 37 months with donanemab.
Rather than solely focusing on statistical improvements in test scores, patients and families can now better understand the potential real-world benefits, such as additional months of managing finances, driving, remembering medications, and preparing meals independently. In the United States, the average annual cost of assisted living exceeds $56,000, while nursing home care averages around $100,000 per year. Extending independence can potentially reduce these costs and alleviate the burden on family caregivers, who contributed an estimated 18 billion hours of unpaid assistance in 2022, valued at $339.5 billion.
The study’s findings may also assist clinicians in having more informed discussions with patients and families about treatment options. When discussing whether to pursue these new medications, healthcare professionals can frame the conversation around the potential for extended independence instead of abstract improvements on clinical scales. It is important to note that the effects of these treatments can vary based on a person’s disease stage and biological factors. For instance, individuals with higher tau protein levels in their brains may experience less benefit from donanemab treatment. Generally, those who initiate treatment earlier in the disease course (with lower CDR-SB scores) tend to gain more additional months of independence compared to those starting treatment at later stages.
“The purpose of this study is not to advocate for or against these medications,” Dr. Hartz emphasizes. “Instead, we aim to provide context regarding the impact of these medications to help individuals make the best decisions for themselves and their family members.”
