P. Murali Doraiswamy is the head of biological psychiatry at Duke University and is a Senior Fellow at Duke’s Center for the Study of Aging. He’s also the co-author of The Alzheimer’s Action Plan, a guide for patients and family members struggling with the disease. Mind Matters editor Jonah Lehrer chats with Doraiswamy about recent advances in Alzheimer’s research and what people can do to prevent memory loss.
What do you think are the biggest public misconceptions of Alzheimer's disease?
The two biggest misconceptions are “It’s just aging” and “It’s untreatable, so we should just leave the person alone.” Both of these misconceptions are remnants of an outdated view that hinders families from getting the best diagnosis and best care. They were also one of the main reasons I wanted to write this book.
Although old age is the single biggest risk for dementia, Alzheimer’s is not a normal part of aging. Just ask any family member who has cared for a loved one with Alzheimer’s and they will tell you how different the disease is from normal aging. Alzheimer’s can strike people as young as their forties; there are some half a million individuals in the United States with early-onset dementia. Recent research has pinpointed disruptions in specific memory networks in Alzheimer’s patients, such as those involving the posteromedial cortex and medial temporal lobe, that appear distinct from normal aging.
The larger point is that while Alzheimer’s is still incurable it’s not untreatable. There are four FDA-approved medications available for treating Alzheimer symptoms and many others in clinical trials. Strategies to enhance general brain and mental wellbeing can also help people with Alzheimer’s. That’s why early detection is so important.
Given the rapid aging of the American population - by 2050, the Alzheimer's Association estimates there will be a million new cases annually - what are the some preventative steps that people can take to prevent or delay the onset of the disease?
Unfortunately, there isn’t yet a magic bullet for prevention. You can pop the most expensive anti-aging pills, drink the best red wine, and play all the brain games that money can buy, and you still might get Alzheimer’s. While higher education is clearly protective, even Nobel Laureates have been diagnosed with the disease, although it’s likely their education helped them stave off the symptoms for a little bit.
My approach is more pragmatic - it’s about recognizing risks and designing your own brain health action plan. The core of our program is to teach people about the growing links between cardiovascular markers (blood pressure, blood sugar, body weight and BMI, blood cholesterol, C-reactive protein) and brain health. A population study from Finland has developed a fascinating scale that can predict 20-year risk for dementia – sort of a brain aging speedometer. Obesity, smoking, lack of physical activity, high blood pressure, and high cholesterol are some of the culprits this study identified. So keeping these under control is crucial.
Depression is another risk factor for memory loss, so managing stress and staying socially connected is also important. B vitamins may prevent dementia in those who are deficient and there are some simple blood tests that can detect this. For the vast majority of people, however, there are no prescription medications that have been proven to prevent dementia. This means that a brain-healthy lifestyle is really our best bet for delaying the onset of memory loss.
In the near future we will likely have prevention plans that are personalized based on genetic, metabolic and neurological information. In familial Alzheimer’s disease, pre-implantation genetic diagnosis has already been used to successfully deliver babies free of a deadly Alzheimer causing mutation—though only time will tell if deleting such dementia risk genes in humans has other consequences.
Your book talks about a new technique that allows doctors to image amyloid plaques in the brain. How will these change the diagnosis of the disease?
Amyloid PET scans are in the late stages of validation testing to see if they can improve the accuracy of clinical diagnosis. The Alzheimer’s brain is defined by beta-amyloid plaques and tangles but, at present, these can only be definitively diagnosed with an autopsy. If an amyloid PET scan is “plaque negative” that will tell a doctor that Alzheimer’s is unlikely to be the diagnosis and help reassure the family. Early findings suggest that people who carry risk genes are more likely to have plaque positive scans even before they develop symptoms - suggesting that the scans could possibly be useful for predicting future risk. If true, this might eventually lead to a change in diagnostic terminology where “preclinical” Alzheimer’s is diagnosed purely based on biomarker and scan findings long before memory symptoms start. Therapies to treat Alzheimer’s by blocking amyloid plaques are already in trials but are currently given blindly to patients without knowing their brain plaque status—raising their risk for side effects and treatment failure. So this scan may also help drug development by helping select the most appropriate subjects for treatment and then monitoring treatment effects. Amyloid accumulation with aging is seen in many animal species and the scan offers us a tool to study what role plaque plays in normal brain aging. So this could do for the brain what colonoscopy did for the gut!
Will science ever find a cure for Alzheimer's?
It’s an incredibly tough puzzle to crack but the pace of research is so great that new drug targets are being reported daily. I think a form of cure is more likely to come from delaying the onset rather than by growing new brain cells to repair lost tissue. Realistically speaking there are several fundamental questions we don’t fully understand and have yet to answer: What causes the disease? Why do plaques and tangles form? Why are the memory centers the first to be destroyed? On the positive side, there are several dozen drugs in clinical trials.
What recent scientific advances in treating or understanding Alzheimer's are you most excited about?
I’m most excited about diagnostic advances. By using a combination of biomarkers, genetic tests and new brain scans, we are inching very close to predicting not only who will develop Alzheimer’s but the exact age when they may start developing symptoms. This offers huge opportunities for conducting prevention trials. Of course, it also brings a whole host of ethical challenges, since our diagnostic and predictive abilities are advancing far faster than our ability to prevent Alzheimer’s.
On the treatment side, there are several developments that I am excited about. The interactions between vascular disease and memory loss suggest that at least some aspects of Alzheimer’s may be modifiable through diet and exercise. Dimebon, a drug that improves mitochondrial function, has yielded promising results and is in final stages of testing. In addition, therapeutic strategies which target the brain’s own ability to repair itself – for example, by delivering nerve growth factor through viral vectors – are in clinical trials. Until we have a cure, however, it’s really important to focus on improving the quality of life of people with Alzheimer’s.