By Jonathan Trobe, MD
The annual symposium of the Greater Ann Arbor Maimonides Society is returning in person. It will take place on Sunday morning, December 4, 2022, in the auditorium of the Kellogg Eye Center at 1000 Wall Street in Ann Arbor.
The topic is Alzheimer’s Disease—what causes it, how to prevent it, and how to treat it, including whether the FDA erred in recently approving aducanumab (Aduhelm).
The speakers are experts in dementia and faculty members at the University of Michigan.
Judy Heidebrink, MD, MS is the Richard D. and Katherine M. O’Connor Research Professor of Alzheimer Disease. She joined the Michigan faculty in 1995, after obtaining a medical degree at the University of Texas Southwestern, and neurology training, a geriatric fellowship, and a master’s degree in research design and statistical design at U-M.
Brian Callaghan, MD, MS directs the U-M Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease) Clinic at U-M. He completed medical studies and neurology residency at the University of Pennsylvania, and fellowships in neuromuscular diseases and in health care policy at U-M, joining the faculty in 2009.
As a preview of their presentations at the symposium, the speakers agreed to answer these email queries:
What is Alzheimer disease? Is it a synonym for dementia, or are there other causes of dementia?
Alzheimer’s disease has an abnormal build-up of amyloid brain plaques and tangles tau protein tangles. This buildup eventually causes problems with memory and thinking. The term “dementia” is used when thinking difficulties interfere with daily functions. Alzheimer’s disease is the most common cause of dementia in older adults, but there are many other causes.
Is Alzheimer disease becoming more common, or is it just that people are living longer or that doctors and patients are more aware of it?
The growing number of diagnoses of Alzheimer’s disease is primarily due to more people living longer, as aging is the greatest risk factor.
Is Alzheimer disease a normal part of ageing?
No. Alzheimer’s disease is different from the thinking changes that occur with aging.
Are we getting any closer to understanding what causes it?
There is not likely a single cause, but rather a combination of the effects of genetics, lifestyle, the environment, and other health conditions.
Are we getting any closer to having an effective remedy or some effective preventive measures?
We do not have a cure, but current treatments can slow the progression of Alzheimer’s symptoms. Prevention strategies for Alzheimer’s disease and other dementias include increasing early life education and maintaining later life social connections.
What happened to the favored idea that beta amyloid deposition causes Alzheimer’s disease?
Although many lines of evidence point to the key role of amyloid deposition in Alzheimer’s disease, there is a poor correlation between amyloid deposition and Alzheimer’s symptoms. This, along with the near universal failure of anti-amyloid therapies in clinical trials, has led the field to explore a much broader range of causes and potential therapies.
What do you make of the scandal involving the scientific research on beta amyloid?
Scientific fraud–in this case potentially falsified data about a “toxic” form of amyloid–is a concern. But it did not significantly impact the direction of Alzheimer’s research.
What happened with the FDA drug approval process of Aduhelm? Did something similar happen more recently with the drug approved for Lou Gehrig disease?
Aduhelm was approved based on a positive effect in one subgroup in one phase 3 trial but not another phase 3 trial. This level of evidence is far below the past standard of the FDA to approve a medication. The FDA approval of the recent Lou Gehrig disease drug (Amylyx) was based on a single positive phase 2 study. Both events point out the changing threshold for approval in the United States in the last several years.
Do you think that the FDA is unduly influenced by patient advocacy or support groups or by politicians?
Yes. For example, the FDA advisory panel initially voted not to approve the Lou Gehrig drug, but upon further pressure from patient advocacy groups, the decision was reversed. Such events lead to the approval of ineffective and costly medications.
Do other countries manage the drug approval process differently than does the United States?
Yes. England and the European Union have two major differences with the United States. First, the standard for approval continues to be two positive phase 3 trials rather than a subgroup or a single phase 2 study. Second, after approval, England requires that the medication be cost-effective.
Does the United States cap the price of drugs?
There are few ways to reign in the prices of drugs in this country. That is why we spend far more for the same medications as compared to all other similar countries.
Are drugs less expensive in the United Kingdom than in the United States?
Yes. Medications are approved about 9 months later in the United Kingdom than in the United States, but are dramatically cheaper after negotiation with the pharmaceutical companies.
The speakers will have a lot more to say about these topics on December 4. The event, which is open to the public and free of charge, begins with breakfast at 9am and ends at noon. Parking is available in an open-air lot next to the Kellogg Eye Center.
You can learn more and register for the event here: https://www.jewishannarbor.org/event/fed-maimonides-event-2/