August 23, 2018

A Giant of Alzheimer’s Research Surveys the State of His Field

Two career achievement awards prompt Dr. Jeffrey Cummings to look back — and ahead

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This year, Jeffrey Cummings, MD, ScD, Director Emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, has received two awards recognizing his illustrious career battling Alzheimer’s disease:

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Dr. Cummings recently retired from the directorship of the Lou Ruvo Center for Brain Health after eight years at the helm (see related article), but he continues as Director of its Center for Neurodegeneration and Translational Neuroscience. Consult QD caught up with him after the July AAIC event and asked him to reflect on Alzheimer’s disease developments during his long career and what’s on the horizon.

Q: You’ve been a leader in Alzheimer’s disease and dementia for about three decades now. How has the field changed?

A: When I started, neurodegenerative syndromes such as Alzheimer’s disease were regarded as a death sentence: Once you were diagnosed, you were doomed to a steady decline until you died from it. When the first drug — tacrine — was approved in 1993, the thinking began to change toward a recognition that there are ways Alzheimer’s disease can be controlled, making it a condition one may be able to live with.

Four drugs are now available for treating Alzheimer’s disease: Three cholinesterase inhibitors like tacrine (which itself is no longer marketed in the U.S.) and memantine, an NMDA receptor blocker.

Imaging and diagnostics have also undergone a revolution. Thirty years ago, diagnosing Alzheimer’s disease was based almost solely on symptoms; now advances in MRI, CT and PET scanning allow us to make the diagnosis with more certainty. We can actually see amyloid protein on PET scans, which is very specific to Alzheimer’s disease. Serum biomarkers have also greatly improved our ability to diagnose the disease early. In addition, PET imaging of tau protein — at this point used only for research — promises to be an important tool for disease staging and therapy monitoring.

Q: What’s coming up next in the field?

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A: We have some challenges to overcome, a chief one being new drug development. No new Alzheimer’s-specific drugs have been approved in 15 years! I think we’re very close to approving two exciting new drugs with a mechanism of action very different from existing therapies. Both are monoclonal antibodies that target beta amyloid, thereby reducing amyloid plaques and slowing neurodegeneration.

Another potential therapy is rasagiline, a drug used in Parkinson’s disease to control motor symptoms. It was noticed that patients taking the drug had improved memory. The data from our clinical trial in patients with Alzheimer’s disease at Cleveland Clinic are now being analyzed, and we hope to publish the findings early next year.

But these advances are not nearly enough. It takes about a dozen years to develop a drug, and time is of the essence for this disease. Increasing the number of clinical trials for promising drugs and getting patients enrolled in them are critical challenges we must address immediately. And we need to investigate more novel drugs targeting specific mechanisms associated with different phases of the disease.

Q: What’s your advice for young scientists or clinicians considering a career focused on Alzheimer’s disease?

A: There are few diseases with a greater potential impact on public health. If nothing more is done to combat it, we are facing 130 million cases worldwide by the year 2050, compared with about 50 million now. The costs of caring for these patients are staggering. Even if only one-third of patients could be helped with new therapies, the savings would be enormous.

A bit of advice drawn from my own experience is to listen carefully to patients and their caregivers, who are the greatest instructors in this field. Only they can tell you what it feels like to have the disease and what they need to make their lives better. Neuropsychiatric issues are especially disabling and can often be ameliorated by reducing anxiety or depression, helping to get a good night’s sleep or addressing delusions. These problems can be more debilitating than memory loss and may be more important to prioritize for treatment.

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Q: How does it feel to have garnered two lifetime achievement awards this year?

A: It’s very satisfying but also terrifying! On one hand, it suggests my work is coming to an end. But the recognition also gives me motivation to continue. Since I stepped down as director of the Lou Ruvo Center for Brain Health, I have more time to devote to science, which is always invigorating for me.

People often ask me if we’re on the verge of a real breakthrough in Alzheimer’s disease. I have stopped predicting, and I honestly can’t say if we’re one step away or 100 steps away. But I do know that in order to progress, we must take the next step.

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