Ask the Expert
Ask the Expert

Eric M. Reiman, MD, Weighs In on Paths to A Cure for Alzheimer’s

Eric M. Reiman, MD

Eric M. Reiman, MD
Executive Director, Banner Alzheimer's Institute 

An estimated 44.7 million people worldwide are living with Alzheimer’s disease and dementia, according to the World Health Organization. Every year, there are 7.7 million new cases, which will continue to rise along with the rising global population of older adults.

This year alone, the U.S. will spend approximately $226 billion on medical and nursing home care not to mention the emotional costs to families of a person with Alzheimer’s.

Given the magnitude of physical, emotional and financial impact Alzheimer’s is having and will continue to have in our lives, we asked Dr. Eric Reiman, executive director of the Banner Alzheimer's Institute and Director of the Arizona Alzheimer’s Consortium, to share his thoughts about the current state of Alzheimer’s disease research and what he hopes for the future.

Do you think that there will be a cure for Alzheimer’s disease in our lifetime? And if not a cure, do you believe that clinicians will be able to intervene and preempt the development of the disease?

A “cure” for Alzheimer’s may be a tall order. We would need to stop the disease, remove existing brain pathology, replace lost neurons and synapses, restore a person’s memory and thinking abilities, and do so completely. However, I am excited about emerging opportunities that will make a transformational difference in the fight against Alzheimer’s, and to do so within the next ten years.

For instance, I am excited about the chance to find effective Alzheimer’s prevention therapies for people who are at high risk of developing the disease. The earlier that a treatment is begun in the course of the disease, the more beneficial it may be. My colleagues and I have been part of the effort to help establish the scientific means and regulatory approval pathway needed to evaluate the range of promising, but unproven, prevention therapies and to find one that works within ten years.

I am also optimistic about the field’s chance to develop effective treatments to slow or stop the progression of Alzheimer’s disease in clinically affected patients, even if it means using a combination of treatments that simultaneously target earlier and later steps in the disease pathway (e.g., extinguishing both the kindling and the fire). There is a growing arsenal of experimental medications and immunization therapies that target the accumulation of a protein called β-amyloid, a cardinal feature of Alzheimer’s. Many (but not all) researchers postulate that β-amyloid plays an important role in the development of the disease. There are a smaller but growing number of experimental treatments that target other potentially important elements of the disease, such as the accumulation, modification and spread of a protein called tau, and particular aspects of brain inflammation and brain metabolism. 

Recently, researchers have raised the possibility that one of the anti-amyloid immunotherapies now in development may remove some of the accumulated β-amyloid and slow down cognitive decline in patients with the clinical diagnosis of mild cognitive impairment due to Alzheimer’s. While their findings should be considered preliminary, confirmation in larger trials would be a great “shot in the arm” for the entire field.

Tell us about your institution’s Alzheimer’s Prevention Initiative (API).

My colleagues and I have had a longstanding interest in the following question: What if a treatment to postpone, reduce, or even completely prevent the clinical onset of Alzheimer’s disease already existed? It would take too many healthy volunteers and too many years to evaluate the range of promising but unproven prevention therapies to see which might ward off disabling memory and thinking problems.

We had previously demonstrated how brain imaging and other biological measurements could be used to detect and track Alzheimer’s in people at genetic risk for the disease, starting many years before the onset of memory and thinking problems. We originally proposed the idea of evaluating promising prevention therapies in terms of their ability to slow down these “biomarker changes.”  We then realized that regulatory agencies like the FDA would be unlikely to approve a treatment based solely on its biomarker effects, until it could be shown that the treatment was “reasonably likely” to predict a clinical benefit. To help address this need, we developed the Alzheimer’s Prevention Initiative.

The Alzheimer’s Prevention Initiative currently includes the National Institutes of Health, philanthropic, and industry-supported prevention trials in cognitively unimpaired individuals who, based on their genetic background and age, are at the highest imminent risk for the clinical onset of Alzheimer’s disease. It also includes an online registry, which provides information about the latest developments in Alzheimer’s prevention research and lets them know about opportunities to participate in prevention trials.

You and your colleagues received worldwide attention for a study about early-onset Alzheimer’s in a Colombian population. Could you tell us more about it?

The Autosomal Dominant Alzheimer’s Disease Trial, which is taking place in Colombia and part of the Alzheimer’s Prevention Initiative, is a partnership involving Banner Alzheimer’s Institute, the University of Antioquia, Genentech/Roche, and the National Institutes of Health. The trial is evaluating an amyloid immunotherapy agent called crenezumab in the world’s largest early-onset autosomal dominant Alzheimer’s kindred. It includes about 5,000 living relatives, almost one-fourth of whom carry a rare genetic mutation that causes them to develop Alzheimer’s disease with virtual certainty and with onset of cognitive impairment at the average age of 44.

In late 2015, we expect to begin a complementary prevention trial. The API APOE4 Trial, a partnership between Banner Alzheimer’s Institute, Novartis, and the NIH, will evaluate two other investigational anti-amyloid treatments, an active immunotherapy and a “BACE inhibitor” that is designed to block the production of different β-amyloid proteins in cognitively unimpaired 60-to-75 year-olds who carry two copies of the APOE4 gene. This gene, which is found in about one-fourth of the population, is considered the major genetic risk factor for developing the more common form of Alzheimer’s at older ages, and people with two copies of this gene have a particularly high (but not certain) risk for Alzheimer’s. The trial is expected to run through 2023.

In addition to testing three promising prevention therapies, the API trials are intended to help advance the study and prevention of Alzheimer’s in other ways. For instance, they are intended to provide a better test of the amyloid hypothesis in clinically affected patients. If these trials fail, it would provide further encouragement for the field to target other elements of the disease. The trials are intended to provide evidence that a treatment’s two-year biomarker effects are reasonably likely to predict a clinical benefit and to provide a public resource of data and samples after the trials are over, helping to provide even faster ways to test the range of promising prevention therapies in the future.

You have said that you are excited about the opportunity to establish a new standard of care. Please explain.

Yes, I am very excited about the creation of a new standard of care for patients and family caregivers, one which ensures that everyone with Alzheimer’s disease and other memory disorders has a proper evaluation, and would more fully addresses both the medical and non-medical needs of patients and family caregivers, leverage new home-based technologies, and serve the entire family’s needs throughout the patient’s illness.

With the emerging change from a fee-for-service to a population-based healthcare financing system, we have an unprecedented chance to establish a new national standard of care, demonstrate that it is financially compelling (e.g., by reducing unnecessary, expensive, and often deleterious hospitalizations), and do so within five years. My colleagues and I hope to help in that endeavor.

It will take a new sense of urgency, an understanding of both the stakes and opportunities at hand, and a determination to act now. It will take new ways for public, private, and philanthropic stakeholders to work together, addressing problems that none of them could address by themselves. It will take new public policies, like those articulated in the National Plan to Address Alzheimer’s Disease, as well as a far greater federal research investment. It will take strategic thinking, a shared sense of accountability, and the understanding and commitment of our national leaders. It will take us all.

I’m extremely grateful to my Alzheimer’s Prevention Initiative colleagues, our NIH, philanthropic, and industry supporters, and our valued research participants. We consider it both a privilege and responsibility to help launch a new era in Alzheimer’s prevention therapies, and find ones that work within the next ten years. There is no guarantee that any of the treatments will work, but there is only one way to find out.


AFAR’s Commitment to Accelerating Research to Find a Cure

The way to find a cure for Alzheimer’s disease is by supporting scientific research in the fundamental mechanisms of its makeup – such as how it forms and progresses and what role aging plays. Knowing the basic biology of the disease is crucial to developing interventions and more targeted treatments that can prevent the disease and offer cures.

Through its many grant programs, AFAR has provided more than $21.2 million to 216 scientists around the world who are making major inroads in Alzheimer’s disease and related dementias. These programs include: the New Investigator Awards in Alzheimer’s Disease, MetLife Foundation Awards for Medical Research in Alzheimer’s disease(AFAR serves as administrator for this program) and our flagship program, the AFAR Research Grants for Junior Faculty.

We also have a wealth of information about Alzheimer’s disease for the public, such as our Infoaging Guide to Alzheimer’s Disease and Aging and Alzheimer’s Fact Sheet.