Many people have heard of brain-related illnesses like Alzheimer’s (ALZ). To mark Brain Awareness Month, we wanted to shed light on ALZ as well as other conditions such as multiple sclerosis in more detail. We spoke with PRA’s psychiatrist Andy Shapira, Director of Medical Affairs, and neurologist Ly Ngo, Medical Director, about their work in Alzheimer’s research and how their experience has informed their understanding of other brain-related illnesses.
ALZ is just one of many brain-related illnesses that we’re highlighting for Brain Awareness Month. Learn more about conditions like MS and public awareness in our latest “Ask the Experts” blog post.
What should the public know about brain-related illnesses, diseases, and conditions?
LN: People often aren’t sure of what neurology treats or what conditions fall under it. Alzheimer's disease, epilepsy, multiple sclerosis (MS), and migraines are very common. It’s important to be aware of the available treatments and when to see a neurologist.
What misconceptions do people have about brain health in general?
LN: When I was in medical school and I decided to go into neurology, I heard many people say, “Why do you even want to be a neurologist? You can't do anything. You can't treat anything.” That isn’t necessarily an accurate view. In many aspects of neurology, such as with migraines and epilepsy, we have come a long way.
On the flip side, there’s Alzheimer’s, which still has a long way to go.
Can you talk to us about your background and your interest in neurology?
LN: I trained at Thomas Jefferson University Hospital (now called Sidney Kimmel Medical College) in Philadelphia, and I completed my medical school and my residency there. I also have fellowship training in neurophysiology, which includes epilepsy and neuromuscular diseases. I had an interest in Alzheimer's because when I went into practice, I practiced as a general neurologist. Alzheimer's was one of the most common neurologic disorders that I saw, especially in the suburbs of New Jersey.
I’ve always had an interest in the geriatric population, especially when pivoting into the clinical trial industry. While I was treating these patients, I became frustrated because once they receive the diagnosis, unfortunately, there isn’t much you can do. You have two different types of medications to offer, neither of which can really stop or prevent the disease.
How does ALZ affect people and their daily lives?
LN: Alzheimer's is the most common type of dementia. Typically, it’s found in the age group 65 and older. However, it can also affect younger patients, which is called early-onset Alzheimer's.
Alzheimer's is a slow, progressive memory loss that typically affects episodic memory. Patients initially have difficulty recalling recent events. There are also genetic risk factors that can increase the risk of developing Alzheimer’s.
People know that caregivers in the family take on an enormous burden when caring for a family member with Alzheimer’s. But I don't think many people realize the scope of the effect Alzheimer’s has on these caregivers. When I used to see patients, there were so many difficult conversations. These patients were independent and self-sufficient for so long. It’s tough to tell them that they shouldn’t drive anymore, or that it isn’t safe for them to live by themselves. Those are always difficult decisions.
When the topic of where the patient should live comes up, one of the options is to move in with a child. However, when asked this question, I would usually receive one of two responses. One is, “I don't want to burden them. I just don't want to do that to my children.” The other is, “I like being by myself and I don't need any help.”
These hard conversations are indicators of the huge burden on the patient as well as the family.
Who does ALZ affect the most? Why does it affect that population more than others?
LN: People with the APOE 4 gene are at increased risk for developing late-onset Alzheimer's, which may have a hereditary component. There are also families who have early-onset Alzheimer's, and they can be tested for the presenilin or amyloid precursor protein (APP) gene.
As far as other risk factors, if they have a history of vascular disorders such as heart issues or strokes, these things can possibly contribute. It is felt that people who are more physically active and those with increased education levels may have less risk than others.
Are there any misconceptions about the chances of getting ALZ if it runs in your family?
LN: For Alzheimer’s, this depends on whether it is late-onset or early-onset. Typically for late-onset, the risk of developing Alzheimer’s is increased if there is a first degree relative with the diagnosis, however, it is not a guarantee that you will have it. For autosomal dominant familial Alzheimer’s, which is a specific type of early-onset Alzheimer’s, if the gene is present then unfortunately the disease will develop.
Can you speak to some of the symptoms of ALZ? What should people look out for?
The most common symptom is memory loss which may start subtly such as misplacing items or forgetting that something is cooking. Some questions that I would ask patients were, “Who balances your checkbook? Who takes care of your bills? Do you ever get lost while going on walks or driving?” It's important to note if the person with the symptoms is finding tasks like these more difficult.
In the beginning, it starts with these little things. As the disease progresses, memory loss is more obvious. They may ask the same questions over and over again and it's easier to pick out the things that seem off.
AS: Like many brain disorders, if you have more than one relative with Alzheimer’s, you are at a higher risk of developing the disorder. Importantly, if you’re having some symptoms early on, the illness might be misconstrued as depression, anxiety, or age-related forgetfulness. These are all things that should alert the family and the individual to get assessed. Earlier assessment and current treatments and behavioral interventions can help.
There is a high background rate of mental illnesses. According to a 2018 study by the National Alliance on Mental Health, 19% of US adults had a mental illness. That's one in five. And 4.6% (1 in 25) had a serious mental illness. It can be difficult to tease that out from Alzheimer’s symptoms early on.
LN: Part of the workup is that you have to rule out anything reversible and any other comorbidity that could be contributing to it. We use neuropsychological testing, brain imaging, and lab work to rule out all the reversible diagnoses before somebody is diagnosed with Alzheimer’s.
According to the ALZ Association, there are an estimated 47 million people worldwide living with Alzheimer's and other dementias. Without a change, these numbers are expected to grow to 76 million by 2030. Can you talk about those numbers and give us some insight into how current research, treatments, and care might reduce the forecasted numbers?
LN: It’s concerning and frustrating that the numbers are growing by so much. There's a lot of work that's being done but unfortunately, there haven’t been any recent medications that have shown a good response for stopping or preventing the disease.
Research is looking at this from a few different angles. Many trials in the past targeted amyloid and tau proteins in the brain, which cause Alzheimer's. Now they’re also looking for new targets. We have a study where the investigational product targets brain metabolism. The focus is also slowly shifting to the preclinical or asymptomatic stages of the disease.
AS: It’s been a long time since the current treatments for Alzheimer's were approved. It’s going on 20 years since we’ve had a new compound approved, even with all of the research and studies going on.
The previous reason for this gap was the need for an exact population of patients with Alzheimer's, which was tricky. But more recently, I think we have better tools. We’re getting more specific and selective. Still, Alzheimer’s is a difficult illness to make significant changes.
LN: Another possible reason why these potential treatments fail is that Alzheimer's is such a complex disease and maybe it’s not just a single target that needs to be addressed.
Why might a misdiagnosis of Alzheimer’s take place?
LN: Since the population is older, they often have many other comorbidities. Pseudodementia, which is depression that can be mistaken for dementia, should be considered in the appropriate patient. You also need to be aware of red flags that would suggest a different type of dementia process. So, in younger people, you always want to do that extra workup, especially if the symptoms are rapidly progressive or if there are any abnormalities in the neurologic exam aside from cognition.
What can you speak to in terms of awareness for other brain-related illnesses, such as Parkinson’s and ALZ?
LN: I honestly think in recent years, the main neurologic diseases that are more common in the population have received good publicity and awareness.
There are frequent events like walks or bike rides for epilepsy awareness, multiple sclerosis, migraines, Parkinson's, and Alzheimer's. The public has become a lot more aware through TV, pop culture, and other media, for example, the show “This Is Us” where one of the main characters has Alzheimer's.
There’s a lot of influence of and portrayal of neurology in the media as well. For example, Michael J. Fox added to that when the news emerged of his Parkinson’s diagnosis. It was especially important because he continued to act and raise awareness of the disease after his diagnosis.
Do you think there's anything lacking from those initiatives? Is there anything that you would like to see more of?
LN: In general, multiple sclerosis is a disease that many people may not understand fully, such as what causes it, and what kind of symptoms exist. I think general awareness of exactly what the disease is and what treatments are available would be important.
AS: Psychiatrically, I would add depression and anxiety disorders. They’re often attributed to situational issues, and these disorders have tremendous disabilities associated with them. There are numerous studies that show this. Even though those areas have received a lot of research and attention over the years, they’re often not fully understood on a personal level. We need to spread the message that getting treatments and developing new treatments is still important in these areas.
When you're talking about something that is as common as one out of five adults having a mental disorder, it's certainly an issue we need to stress.
Can you describe in a little more detail what MS is?
LN: Multiple sclerosis is an autoimmune disorder of the central nervous system. Multiple sclerosis typically occurs in women. It often occurs at a young age and these patients can present with a wide range of neurologic symptoms including vision loss, weakness, and sensory loss.
The diagnosis can be difficult because there are specific criteria for an official MS diagnosis and the episodes need to be separated by time and space.
The medications have come a long way and a lot of them are effective at significantly slowing the progression of the disease.
Can you talk about the differences between ALS, MS, and Parkinson’s?
LN: Multiple sclerosis is an auto-immune disorder which was touched on earlier, ALS is a neuromuscular disorder, and Parkinson's is a movement disorder. All of these diseases are difficult and complex. However, for MS and Parkinson’s, a lot of patients with mild to moderate disease can still live fairly normal lives with or without medication. In contrast, for ALS, which is a slow loss of muscle function including the diaphragm for respiration, the course of the disease is quite devastating. There are only a few medications for ALS available and treatment is still mostly supportive.
Parkinson's is a movement disorder, so patients have difficulty with initiating and sustaining movement. There is the characteristic pill-rolling tremor and the current treatments, such as Levodopa/Carbidopa, are very effective at treating the symptoms.
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