World Dementia Council Update Lessons from Treatment: Treatment Series

Abstract

The field of Alzheimer's disease treatment has entered a pivotal new era with the approval and utilization of new disease-modifying treatments across many countries. Although these treatments do not yet offer a cure, they hold promise in slowing disease progression and offering hope to the millions of people around the world affected by this disease. Despite these treatment advances, there are many unknowns related to the global implementation of these therapies as well as issues of equity and accessibility.

To discuss these barriers, successes, and share lessons learned, the World Dementia Council (WDC) held the first of three virtual dialogues focused on the era of treatment on January 23, 2025.

Following opening remarks from Lenny Shallcross, Executive Director of the WDC, session co-chair, Dr. Phillip Scheltens, Emeritus Professor and Head of the Dementia Fund at EQT Life Sciences in Amsterdam, Netherlands, introduced some of the key questions to be addressed in this new era of treatment: Who to treat? When to treat? How to address side effects? When to start treatment? When to stop treatment? These questions, among others, helped guide the subsequent discussion focused on sharing lessons learned across the Alzheimer's disease treatment landscape.

The remainder of the dialogue included reflections from global researchers on early learnings from treatment delivery and a robust full-group discussion on how these lessons can be translated and expanded globally.

Dr. Reisa Sperling, Professor of Neurology at Harvard Medical School and Director of the Center for Alzheimer's Research and Treatment discussed the progress in Alzheimer's disease treatment. She acknowledged that although current treatments are not perfect, the ongoing and upcoming Phase 3 clinical trials, like TRAILBLAZER-ALZ 3, offer promise. She also highlighted the growing interest and opportunity surrounding combination trials, particularly those targeting both amyloid and tau, which could offer even greater benefits.

She addressed an important area of focus for researchers, the side effects of these treatments, most pointedly, ARIA (amyloid-related imaging abnormalities), which can refer to swelling and bleeding in the brain. Understanding the avenues to most effectively manage and avoid ARIA is becoming increasingly important, and recent research exploring adjusting titration of treatment as a way to reduce the risk of ARIA has indicated that progress is being made in the space.

Looking toward the future, Dr. Sperling emphasized the importance of early intervention and primary prevention efforts including clinical trials like the AHEAD Study, which is exploring whether treatment can slow or stop early brain changes due to Alzheimer's disease in cognitively normal adults who are at higher risk of developing the disease in later life. Finally, she called on the research world to take a renewed focus on understanding the inequities of Alzheimer's disease and the disproportionate risk faced by communities of color. Because biomarker and imaging data do not explain these disparities, she urged researchers to explore other contributing factors to improve outcomes.

Dr. Gil Rabinovici, the Edward Fein and Pearl Landrith Distinguished Professorship in Memory and Aging at UCSF, described his team's experience administering of amyloid-targeting therapies to patients at the UCSF Memory and Aging Clinic. The UCSF Memory and Aging Clinic is a proven leader in administering similar types of therapies, has significant experience with biomarkers and conducting clinical trials, and is staffed by a comprehensive care management team including physicians, neuropsychologists, social workers, nurses, and other allied health professionals. However, despite this strong foundation, the implementation and capacity building required to implement treatment in the clinic proved to be a substantial effort.

Working in collaboration with their health system, the team developed a detailed protocol to identify eligible patients. This process includes a primary evaluation by a dementia specialist to assess severity and a multidisciplinary review team to determine appropriateness of treatment. If deemed eligible for treatment, patients then receive additional clinical testing, longitudinal care management, access to a call line to address ARIA and other side effects, and ongoing assessment of treatment appropriateness — all of which had to be built up.

This more conservative protocol has resulted in a small subset of patients being selected to receive Aβ-Targeting Therapy (ATT). However, the associated increase in clinical testing, particularly biomarker use, along with the significant investment in new infrastructure and close coordination with health systems and other specialties, is expected to improve patient care and strengthen the health system's capacity for future treatments.

Dr. Donna Wilcock, Director of the Center for Neurodegenerative Disorders at the Indiana University School of Medicine, shared similar insights into how her team is delivering therapies to patients with Alzheimer's disease through the Indiana University (IU) Brain Health Program.

The IU Brain Health program, like the UCSF Memory and Aging Clinic, developed a rigorous protocol to identify eligible patients for therapy. This process includes a referral to the IU Brain Health Program, assignment to a brain health navigator, cognitive testing, magnetic resonance imaging (MRI) screening, positron emission tomography (PET) or cerebrospinal fluid (CSF) tests, apolipoprotein E (APOE) genotyping, and consultations with a behavioral neurologist to discuss risks and benefits of treatment. Approved patients are then routed through the prior authorization team and initiate treatment. A dedicated social worker was also added to the team to further enhance patient navigation, care management, and patient needs.

Dr. Wilcock concluded by highlighting the significant time and effort required to build this program from the ground up. She also stressed the importance of close collaboration, coordination, and support from health systems to ensure successful and sustainable treatment delivery.

Dr. Cath Mummery, consultant neurologist at University College London, concluded the opening reflections by discussing experiences from the UK. Although approved, these treatments are not yet available through the National Health Service (NHS), so open communication and sharing lessons learned from across the globe are invaluable as the UK develops its own infrastructure and treatment protocols.

Dr. Mummery highlighted critical challenges in ensuring equitable access to not only the treatments, but also to early detection and diagnosis, and care navigation services. Addressing these inequities should be a priority for all clinicians and researchers, as it is meaningless to have an approved treatment without the infrastructure and systems in place to effectively provide them.

Along with improving access, educating the public is another crucial step, as perceptions of the treatments vary across the country. Enhancing understanding about these treatments and the benefits they may have will also help elevate Alzheimer's disease research and care as a national priority, gaining support from policymakers, the media, local clinics, and the broader public.

Amplifying patients’ voices must also remain a priority. Leveraging lived experience stories and harnessing their influence can help shift public perception and highlight the importance of delivering the best care possible, regardless of a patient's eligibility to receive treatment. Continuing to share global learnings on treatment and infrastructure development will help the UK, and other countries, better prepare for delivering these therapies in the future.

Following the reflections from researchers, session co-chair, Dr. Maria Carrillo, chief science officer at the Alzheimer's Association, led the full group discussion. The discussion highlighted the many challenges and opportunities in implementing these therapies on a global scale.

Equity remained a central theme, specifically with respect to access and funding for clinical trials and treatments in Africa. In regions without access to approved treatments, and even in those that do have access, primary prevention and risk reduction efforts must remain top priorities. Studies including U.S. POINTER and LatAm-FINGERS, both multidomain lifestyle intervention trials, will provide important information about which interventions may be successful in slowing or preventing cognitive decline.

The group also emphasized the critical role of infrastructure in delivering these therapies. Some of the most significant infrastructure demands include building and recruiting a skilled workforce, improving access to infusion centers, developing new technologies to more efficiently detect ARIA and other side effects, and simplified diagnostic measures like the use of blood tests rather than CSF. Addressing these demands and investing in solutions may help alleviate bottlenecks in treatment and improve the experience for patients and clinicians.

Finally, the need for clear communication and ongoing education was emphasized. It is critical for the public, media, policymakers, and the broader health care system to understand that although many people are living with Alzheimer's disease, not everyone will be eligible for treatments. Managing expectations and addressing misconceptions about the burden on the health care system due to treatment approval and availability will continue to be a priority. It is imperative that researchers share their learnings and disseminate trusted, peer-reviewed research to help build this awareness.

Although challenges remain in accessing and administering treatments, the discussion highlighted the promise and opportunity that these treatments provide for the future. By publishing and sharing lessons learned from other diseases and from the ongoing work in the Alzheimer's treatment space, health systems can appropriately prepare to effectively treat and manage care for their patients with Alzheimer's disease around the world.

This was the first of three dialogues focused on the era of treatments that will culminate at the 2025 WDC Summit held in London, England in March. Summaries from these and other WDC dialogues and events will be published over the coming months.

To learn more about the WDC, please visit worlddementiacouncil.org or email Lenny Shallcross, Executive Director, at [email protected].