The Advisory Council on Alzheimer’s Research, Care, and Services presented updates on Alzheimer Disease (AD) and AD and related dementias (ADRD) treatments and ongoing AD research in a virtual meeting held in January.
Representatives from the National Alzheimer Project Act (NAPA) research committee, Washington University School of Medicine (WashU), and the Alzheimer’s Association reported on the developments in disease modifying therapies (DMTs), funding, resources for dementia caregivers, and the connection between AD and Down syndrome.1
DMTs for AD
From 2016 to 2023, researchers have observed advancements in AD treatment. Most recently, the US Food and Drug Administration’s (FDA) approved Leqembi (lecanemab), an amyloid beta-targeting antibody for patients with AD and those in the mild cognitive impairment (MCI) or mild dementia stage of the disease. The FDA’s decision on donanemab, also an amyloid beta-targeting antibody, for the treatment of patients with early AD, is anticipated in the first quarter of 2024.
The approved route of administration for lecanemab is intravenous (IV). Eisai Pharmaceuticals is testing a subcutaneous route of administration. Compared with the IV route, initial reports suggest that subcutaneous formulations clear 14% more plaque, have a 11% higher area under the curve (AUC), and have lower systemic injection reaction rates.2
On January 31, 2024, Biogen Inc. decided to discontinue Aduhelm (aducanumab-avwa) production, sales, and the affiliated clinical study. Instead, they will allocate their resources to the development of other treatment methods for AD and prioritize moving forward with lecanemab.3
Growing Resources for Dementia Caregivers
With recent progress in AD treatments, progress has also been made in the availability of resources for dementia caregivers. The Alzheimer’s Association collaborated with the Centers for Disease Control and Prevention (CDC), Building Our Largest Dementia (BOLD) Public Health Center of Excellence on Dementia Caregiving, and Emory University to initiate a free interactive public health curriculum for clinicians, students, and educators. The goal is to increase awareness and knowledge about the importance of dementia caregiving and how public health may affect it.
Representatives of the advisory board addressed further initiatives concerning racial/ethnic diversity needs between patients and caregivers and demanded an increase in caregiver wage. Although a resolution has not been reached, caregiving networks are optimistic to find ways to implement changes in the near future.4
The research and the investments that have been made over the past decades led to these advancements in understanding the disease, how it starts and progresses, and figuring out ways to intervene in it.
Revisions and Updates to Funding AD Research
Various extensions and reauthorizations have been made to continue AD research. There is bipartisan agreement that AD research needs more attention. The National Institutes of Health (NIH) and CDC are looking to:
- Extend and reauthorize the National Alzheimer’s Project Act (NAPA)
- Continue advising the Center for Medicare and Medicaid to implement a dementia care management model
In the fiscal year 2024 senate budget requests, the NIH requested a $321 million increase and the CDC requested $35 million for the BOLD infrastructure for the Alzheimer Act. The Act focuses on AD diagnosis, treatment and dementia caregiving.5
Increases in federal funding have advanced AD research and the progression of clinical trials. “It’s research that changes the cookbook of medicine … The research and the investments that have been made over the past decades led to these advancements in understanding the disease, how it starts and progresses, and figuring out ways to intervene in it,” Randall Bateman, MD, Charlotte and Paul Hagemann distinguished professor of neurology at WashU in St. Louis, said at the meeting.6
Challenges in AD Research
Researchers at the Washington University School of Medicine have identified challenges that have limited treatment objectives.7
|Overall Barriers to AD Research
|Racial & Ethnic Disparity
|– Racial and ethnic groups are excluded from testing
– Overall lack of research about patients with AD who belong to racial and ethnic groups
|Accessibility to Infusion Centers
|– Patients who live in rural areas have difficulty accessing infusion centers
– Infusion treatments are time consuming. Patients often miss due to vacation, travel, and other illnesses
– 6–8-month waitlist for treatment
– Small window for treatment
|Cost of treatment
|– Treatment costs $50,000 per year
– Medicare finances only 80% of treatment expenses, which could leave patients with ~$10,000 bill out of pocket
– AD biomarker testing is not offered insurance coverage
|Effectiveness of DMT Treatment
|– Need for precision medicine for an individual’s unique disease profile
– Dosage and duration vary per patient
– Some patients need to switch medications
Although limitations are presented in the infrastructure for AD/ADRD treatment, the researchers highlight initiatives for AD prevention. These include early administration of lecanemab and the implementation of the combination of DMTs.8
The Connection Between AD and Down Syndrome
In highlighting the existing challenges with AD treatment, Elizabeth Head, MA, PhD, and professor at the University of California, spoke about the connection between AD and Down syndrome (DS). By age 40, patients with DS have sufficient plaque and tangle pathology for a diagnosis of AD. Dr Head mentioned that it is widespread for older patients with DS to develop AD, and it is one of the leading causes of death for this patient population.
Though there is a connection between AD and DS, patients with DS are often excluded from AD trials, presenting a barrier in research. Ultimately, there is a lack of racial and ethnic diversity in trials; only White patients have a higher survival rate.
Since there is still a limited amount of evidence, it is difficult to conclude pharmacologic intervention effectiveness for cognitive decline in patients with DS. Dr Head urged that researchers could begin to expand AD studies to this patient population. The inclusion of patients with DS in cohort trials would result in advanced AD research and a better understanding of DS.9