It’s been twenty-five years since medical researchers came to an agreement about what Alzheimer’s disease looked like, leading to a major effort to try to understand its causes and, ultimately, to find a cure. Those with family members affected by the disease have seen good news and bad news this year: Promising research points to the possibility of earlier diagnosis, but a major late-stage drug trial was shut down because the therapy was found to be ineffective.
Kathleen Welsh-Bohmer ’79, director of Duke’s Joseph & Kathleen Bryan Alzheimer’s Disease Research Center, puts the recent findings in perspective.
Do we know what causes Alzheimer’s disease?
We’re not entirely sure, although we have a lot of information. We know that genes we inherit can influence our susceptibility to Alzheimer’s disease. Some extraordinarily rare genes have been identified that can cause the illness in some families, but those genes account for less than 1 percent of the cases that we see clinically.
We expect that Alzheimer’s disease is a chronic illness that occurs over decades, probably beginning in middle age, and continuing on a slow, indolent course for many years. The genes we inherit interact with things that we’re exposed to in everyday life as well as medical conditions, which together can result in progressive brain compromise and loss of cells that are related to the appearance of Alzheimer’s symptoms.
And there’s still no cure?
That’s correct. We don’t currently have a cure.
What we do know is that there’s tremendous variation in terms of the age that people develop the illness and how quickly the illness may progress. Various health conditions may accelerate or protect against or slow down the course of the illness. We can treat some of the risk factors, such as heart disease and hypertension, to try to maintain optimal brain health.
It seems as if every week there's a new food or lifestyle choice touted as preventing Alzheimer's. Is there any validity to these?
Recently there was a forum held by the National Institutes of Health to examine evidence about prevention of Alzheimer's disease, and the current information is that these approaches do not stop the illness. But it certainly doesn't hurt to try.
Getting physical exercise is good for brain health and so are things like engaging one's intellect or socializing. These habits are associated with good, all-around physical and emotional health even if they ultimately prove not to prevent Alzheimer's specifically.
A recent late-stage clinical trial for an Alzheimer’s drug therapy was canceled because the drug was ineffective. Can you talk a bit about that?
This was a big disappointment. The hypothesis was that the abnormal accumulation of amyloid protein was creating this gunk in the brain, basically clogging brain circuits and causing cell death. By targeting treatments that would eliminate this accumulation, you could prevent the neuron destruction that was occurring.
The particular drug that was developed was designed to do exactly that. Unfortunately, it was not effective in slowing down the clinical expression of Alzheimer’s disease. The trial was done in patients who already had clear diagnoses, and it may be that the compound, if it was effective, was started too late.
Do you think there’s a lack of awareness in our country about Alzheimer’s disease?
Our country has been very slow to realize that we have a national epidemic on our hands. It’s a late-onset illness, so a lot of what’s been seen with Alzheimer’s has been chalked up to the effects of normal aging. But Alzheimer’s disease is not normal aging. It’s affecting 5.3 million Americans and, by 2050, is expected to affect 15 million Americans. It currently costs our nation $172 billion annually, and the toll on families and individuals affected by the illness, losing the very essence of what makes us sensitive humans, is a national tragedy.
Why is the cost of Alzheimer’s care so high?
The individual who’s losing the ability to function independently will require not only ongoing medical care but also the services of a caregiver. Often that means a family member—either a spouse or an adult child—who needs to be available to take care of the individual around the clock, meaning lost wages. And this is an illness that can last anywhere from ten years to many more than that, sometimes decades.
Can you tell me a little about the current push to have new criteria for making a diagnosis of Alzheimer’s disease?
We used to diagnose the illness once people were very clearly affected and impaired, whereas we’re now able to make the diagnosis much earlier.
The new criteria, still under development, break the illness into three different stages: the latent, or silent, stage; the preclinical, or prodromal, early symptomatic stage; and then the fully expressed dementia stage. Diagnosis at each of these stages is based on clinical characteristics but also includes laboratory and biomarker findings that can facilitate or augment the diagnosis, which is particularly important in the very early symptomatic stage.
As is the case with many chronic illnesses, if we’re able to identify people very early in the course of the disease, then we can target our drug treatments at the triggering events and potentially prevent Alzheimer’s altogether.
Can you predict whether a person will get Alzheimer’s before he or she starts exhibiting symptoms of memory loss?
This has been a really exciting time in the development of diagnostic tools. Recent investigations examined specific proteins within the cerebrospinal fluid that have been found to be associated with Alzheimer’s disease. The hypothesis is that levels of these particular proteins, amyloid and tau, which accumulate within the brain and cannot be cleared, could be measured within the cerebrospinal fluid, reflecting what’s going on in the brain. What has been recently shown is that the ratio of these key proteins is highly predictive of individuals who are developing the illness.
It’s not a perfect test yet, so it can’t be used as a basis for treating patients. But certainly it’s a very important finding that will advance our ability to develop therapies to be used in the early stages of Alzheimer’s disease before the symptoms are even clinically manifest.
What’s particularly promising in Alzheimer’s research?
I think the promising areas have come from both our successes and our failures, which have caused us to look at this disease differently in biological terms, and we’re now finding new, potentially exciting ways to preserve brain function. Some novel therapeutics that are under clinical development right now may have the potential to be used in midlife or later to prevent the illness.
The new developments in brain imaging are also very exciting and very helpful. They provide an early glimpse into the brain to see what’s happening with the neural circuits that are involved with the illness. The technique is based on imaging the abnormal proteins that collect in the brain. We’ve developed chemical tags that bind to the amyloid and contain a fluorescent compound which allows us to visualize areas in the brain that show a high accumulation of this abnormal protein.
I think that’s encouraging and will provide us with tools to better diagnose the illness early and intervene early.
This interview was conducted, condensed, and edited by Aaron Kirschenfeld.