The Dawn of New Alzheimer’s Treatments: Embracing a Multimodal Approach

Dr. Howard Fillit, the Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF), authored an op-ed, "An Alzheimer’s Advance, Not a Cure-All: Donanemab promises progress. The FDA shouldn’t hold out for perfection," that appeared in the Wall Street Journal. Dr. Fillit underscores a critical paradigm shift in Alzheimer’s research and treatment: the need for a multimodal approach to combat this multifaceted disease.

The Complexity of Alzheimer’s Disease

Alzheimer’s disease is not a single-pathway ailment. It is characterized by various misfolded proteins, metabolic disturbances, and vascular dysfunction.

"It’s important to recognize, however, that treatment isn’t so simple. Alzheimer’s is characterized by the presence of several misfolded proteins, as well as aging-related impairments, including metabolic disturbances and vascular dysfunction."

Historically, treatments have primarily focused on the amyloid hypothesis—targeting the amyloid-beta plaques that disrupt brain cell function. While this approach has yielded some progress, exemplified by drugs like Leqembi and the potential FDA approval of donanemab, it remains only part of the solution.

Dr. Fillit aptly draws a parallel to the evolution of cancer treatment. In the late 1940s, Sidney Farber’s use of aminopterin for leukemia marked the beginning of chemotherapy—a treatment initially met with skepticism but now a cornerstone of cancer care, often combined with radiation and immunotherapy. Similarly, Alzheimer’s disease requires a broad-spectrum approach that addresses its multiple underlying pathologies.

The Role of Vascular Health

A significant yet often underemphasized aspect of Alzheimer’s disease is its connection to vascular health. Research consistently shows that conditions compromising cardiovascular health, such as hypertension and diabetes, increase the risk of cognitive decline and Alzheimer’s disease. In fact, studies reveal that individuals with Alzheimer’s often experience reduced blood flow to specific brain regions, which can precede dementia by years.

Addressing vascular dysfunction is crucial. Improving vascular health not only supports overall brain function but also helps manage the metabolic and amyloid pathologies of Alzheimer’s. For instance, a study published in the Journal of Alzheimer’s Disease reported that medications targeting vascular health can enhance cognitive function by 15% in individuals at risk for dementia.

A Multifaceted Treatment Strategy

Given the complexity of Alzheimer’s, future treatments must include a combination of therapies addressing amyloid-beta, tau proteins, and vascular health. Anti-amyloid drugs should become part of the standard of care, but the ultimate goal is a comprehensive treatment regimen that tackles all aspects of the disease.

Dr. Fillit’s call to action is clear: the FDA should not let the pursuit of perfection hinder progress. By continuing to invest in research and development, particularly in vascular health, we can build an arsenal of therapies that offer hope to millions affected by Alzheimer’s disease.

Conclusion

As we stand on the cusp of new advancements in Alzheimer’s treatment, it is imperative to embrace a multimodal approach. By acknowledging and addressing the disease’s various facets, particularly the crucial role of vascular health, we can make significant strides in combating Alzheimer’s. Dr. Fillit’s leadership and advocacy for comprehensive treatment strategies pave the way for a future where Alzheimer’s no longer robs individuals of their memories and identities.