We asked, and you answered! Below you will find a Q&A with Dr. David Knopman in our Alzheimer’s Association International Conference (AAIC) feature “Ask the Expert.” We asked you to share what you would ask a researcher if you had a chance, and you asked important probing questions regarding Alzheimer’s symptoms, diagnosis, treatments and advancements. Read all of the questions and answers below.
Is a brain autopsy still the only way to definitively diagnose Alzheimer’s disease?
That’s a great question, one that I’m asked almost every day. It’s not true now.
One of the great advances that have been made over the last 10 years in Alzheimer’s research is the availability and use of imaging – brain scans, spinal fluid analysis – so that we can now, at least on a research basis, diagnose Alzheimer’s disease in life. From a practical point of view, that may not apply to a patient being seen in a clinic, but these results that have been accomplished in real-time have informed us about how good – or not so good – our diagnoses are when they are just based on a history from a family informant and the examination of the patient. In fact, a clinical examination based on the patient history and the exam is pretty good for diagnosing Alzheimer’s disease and dementia. It’s not perfect, however, and on the research level, we aspire to achieve a much higher level of perfection.
I want to emphasize that while understanding the cause of the cognitive impairment/dementia isn’t necessarily 100% accurate, diagnosing Mild Cognitive Impairment (MCI) or dementia can be extremely accurate.
What are some of the biggest advancements in our understanding of Alzheimer’s in the past couple of years? Are we getting close to a cure?
Prior to 10 years ago, most of the work that was done in understanding the biology of Alzheimer’s disease required people to have died so that we could examine their brains under a microscope. With the advent of advanced imaging techniques such as positron emission tomography (PET) scans, making better use of MRI scans, and using spinal fluid analyses, we are now able to plot out the course of the disease in living people before they have symptoms, as they’re developing symptoms and once their symptoms become more advanced. This has been an important piece of progress because now we can look at patients and understand what is going on in their brains in real-time.
While this hasn’t led to a cure in 2015, it has certainly advanced the game tremendously. In virtually all of the clinical trials being done with anti-amyloid therapies, amyloid imaging with PET scanning is a requirement to ensure that we know that we are treating people with the biology of Alzheimer’s disease. This requirement only came about because of the advances we’ve made in the past couple of years.
How much does genetic testing tell us? If other family members have Alzheimer’s, what are my chances of getting it?
There are three genes in which mutations are known to cause Alzheimer’s disease with a very high likelihood, but it’s important to recognize that the number of families that have a mutation in one of these three genes is extremely rare – only about 500 families globally.
On the other hand, there are genes such as APOE – the best known and most important – which are actually very common in the general population but have a much lower likelihood of causing Alzheimer’s if someone happens to have the “bad” variant.
If you have a family member with Alzheimer’s, find out who diagnosed that person and whether or not that person had an imaging or autopsy confirmation the disease. If there was no proof of diagnosis, more questions should be asked about what the underlying cause might have been. However, if there is reasonable certainty that this is a familial or genetic disease, there is testing commercially available that is highly accurate. Talk to your physician and then see a medical geneticist for definitive testing.
If it can be determined that Alzheimer’s starts around 10 years before symptoms begin, is there an opportunity to treat it before symptoms starts?
The answer, we hope, is yes.
In fact, worldwide, there are four studies trying to do that. One I am involved in, the A4 study, accepts individuals between the ages of 65 and 85 in order to perform amyloid PET imaging; if individuals have elevated levels of amyloid, they are eligible for the study. This study is funded by the National Institutes of Health (NIH) with contributions from the Alzheimer’s Association and Lilly Pharmaceuticals.
A second trial involves a very small group of people with the autosomal dominate inherited mutations that is ongoing and recruiting individuals who are asymptomatic.
An exotic study taking place in the country of Colombia focuses on a very large extended family carrying a genetic mutation that consistently causes Alzheimer’s in family members. These families have teamed up with researchers in the U.S. and Colombia to perform clinical trials using anti-amyloid drugs.
The fourth trial, the Tomorrow study, is also seeking a similar approach. This is a very exciting area; we now have the tools to complete a study in people while they are symptomatic; we simply did not have these tools a few years ago.
Why is the rate of decline for some people with Alzheimer’s so much faster than others?
This is a question that we still can’t answer today as there is a lot of variability from patient to patient. By being able to look at the biology of the disease in living people through imaging and spinal fluid biomarkers, I hope that that answer will eventually be revealed to us.
Age makes a difference, and other health issues make a difference, but beyond that, there are some very important features of the disease that determine the rate that people progress at that we still don’t know.
Are there promising results for any drugs currently being investigated for treating Alzheimer’s?
Yes. To be honest, the results we’ve heard at AAIC aren’t going to translate into available therapies next week or probably even next year, but what I’ve heard regarding several drugs presented is very encouraging. While there is nothing definitive at this point, we are better at conducting the trials, we’ve learned how to enroll the right patients and we do things better overall.
It is difficult to know the right dose without testing; sometimes there are failures and sometimes there are successes. It is difficult to know what the side effects will be until we test in humans. This is an arduous process of finding drugs that work for this complicated, variable and heterogeneous disease, but I believe the results presented at AAIC are promising. Though I am hopeful, I don’t want to raise expectations too high.
What do you think about the use of ultrasound as a treatment for Alzheimer’s? A recent study with laboratory animals appeared to show promise.
This is not going to be suitable for humans for a long time. That said, it’s an exciting idea, and I am open to any idea that might have value. This study was done in rodents; to scale it up and begin to test it in humans is very expensive. There are questions about safety, dosage, number of treatments – and these are the kind of things that need to be done. I hope that the investigators behind this study will have a strong enough scientific rationale and find success in funding to see if this idea works. At this point, it is still very early for that particular approach.
Finding a cure is the ultimate goal. The World Dementia Council and other U.S. organizations have set a goal of accomplishing this by 2025. What are your thoughts on this goal?
Yogi Berra is quoting as saying: “It's tough to make predictions, especially about the future,” but I am hopeful that we are continuing to make progress. More importantly, there is more funding that is going towards research. The number of promising projects that we can fund at this point may be very low, but with private and federal funding sources, we hope we can pursue many other avenues. Funding is what is going to increase the likelihood that we will find a cure by 2025.
About David Knopman, M.D.:
Dr. Knopman earned his M.D. degree from the University of Minnesota (UM) Medical School, where he also completed his neurology residency. This was followed by a fellowship in behavioral neurology at Hennepin County Medical Center and UM. He was a faculty member at the University of Minnesota from 1980 to 2000. Dr. Knopman joined the Department of Neurology at the Mayo Clinic, Rochester, Minnesota, in 2000, where he is currently professor of neurology, Mayo Clinic College of Medicine, a consultant in Neurology at the Mayo Clinic, and a co-investigator in the Mayo Alzheimer’s Disease Research Center. His research and clinical interests have been in dementing illnesses. He is an author on more than 300 articles on various topics in dementia. Dr. Knopman is deputy editor of Neurology, the journal of the American Academy of Neurology (AAN). He was the senior author on the 2001 AAN Practice Parameter on the Diagnosis of Dementia and was co-chair of the National Institute of Aging-Alzheimer’s Association workgroup that drafted the revised criteria for Alzheimer’s disease dementia. Dr. Knopman joined the Alzheimer’s Association Medical and Scientific Advisory Council in 2012.