Tag Archive for: dementia

Running through a diagnosis of dementia

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Toughness might as well be Tom White’s middle name.

He served nearly five years in the U.S. Marine Corps. In 33 years with the Jacksonville (Florida) Sheriff’s Office, he worked his way up from patrolman to detective. He learned SCUBA rescue. When he retired from that gig, he spent 10 years working in other law enforcement posts, mostly as a fire marshal. Tom always has served the public, always given back.

In his spare time, Tom is an avid runner. About 10 years ago, he and his wife Becky challenged each other to run road and trail races in every state. They were well on their way until 2022, when Tom received a dementia diagnosis that rocked his world. Tom wasn’t about to let the disease derail his goal. So, with the blessing of his doctor, the dynamic duo kept on running.

As of this writing (early September 2023), the Amelia Island, Florida-based couple has completed races of varying lengths in 33 states. They recently wrapped a race in Alaska, under the midnight sun. They’re registered for races in Oregon and Washington before October begins.

“We’ll keep going until we can’t go anymore,” the 74-year-old Tom tells BrainWise. “I don’t care what the doctor tells me. There’s no way I’m giving up on life.”

Becky, 71, agrees.

“We may not be as fast as either one of us was years ago, but we’re still competing, still participating, and still finishing these races as best [as] we can,” she says.

Love of culture

Sure, Tom loves the endorphin rush of running a race. In his earlier days, that and a competitive spirit would propel him through marathons several times a year. As Tom aged, his interests matured, and he became less focused on the race itself and more focused on the culture that racing inspires.

One year—2003, to be exact—Tom came up with an idea of racing with a camera and taking pictures of what runners see from the course. These images captured fellow runners in grief and agony, spectators cheering on loved ones, and more. According to Becky, he became known as “the runner with the camera,” and everybody knew his name.

“People get pictures of the finish line, but they don’t ever get images of what’s going on during the race,” says Becky, who worked for years as a photographer for the Jacksonville Times-Union herself. “Once Tom started taking these pictures, everybody loved it because it was different and unique.”

Tom’s photos were published in Becky’s newspaper. Later, the local news station spotlighted his work.

Feedback on the photos was overwhelmingly positive. In subsequent races, runners and spectators would cheer for Tom every time he strode by.

Love of travel

Tom still races with his camera, though he isn’t taking many pictures anymore, and the race distances have shortened from full marathons (26.2 miles) to halves (13.1). Now he also has other priorities, such as maintaining his balance on the course and finishing each race so he can cross more states off his list.

He and Becky both say they love the new challenge because it enables them to see the world.

“It’s not so much about staying in shape as it is about being together and seeing all of these new and exciting places we’ve never seen,” Becky says. She adds that her personal objective every time they book a new race is to plan the trip so they can get out and see interesting attractions in or around the race destination.

To find sights to see, Becky investigates websites such as Atlas Obscura and Roadside America.

When they traveled to Illinois for a marathon, for instance, Becky discovered the race was near a tiny town named Metropolis, which was inspiration for the home of Superman. When they traveled to the western United States, they saw the Grand Canyon and Mt. Rushmore.

“Every place we go we find something unique and memorable,” Tom says.

Love of storytelling

Upon returning home, Becky prints out pictures and puts together photo books as mementos of their trips. Becky decorates each book to reflect something from the trip.

For example, on the front of the book from a trip to Louisiana is a picture of a crawfish.

Becky notes that the books serve two purposes: To tell stories of the couple’s adventures and to collect memories so Tom can access them easily if he needs to. She adds that the books are symbols of their love, too.

“There aren’t a whole lot of husbands and wives who do this together,” she says with a tremble in her voice. “We always do it together, at the same pace, which means he’s usually going slower for me. There’s no competition. Instead, there’s cooperation. We’ll say, ‘Give me a hand’ or ‘I’ll pull you up.’ We enjoy it more because we do it together. There’s no pressure that way.”

What’s next

Tom and Becky say they’ll keep running races as long as they can.

Becky says the two of them probably shouldn’t be running half-marathons any more, but they’re still doing it for now. She says she envisions a time in the near future where the duo might downgrade to 10- or 5-kilometer races instead. She adds that the distance doesn’t matter.

“Tom and I always say, ‘It’s you and me from here on out,’” Becky notes. “It’s important to nurture that, I think. I will always be here for Tom and he will always be here for me, no matter what. We treat each other with respect and dignity. We support each other. Really, that’s all you can ask for from a partner in this life.”

Tom agrees. He adds that once he and Becky hit all 50 states, they plan to start visiting the home nations of their ancestors, which include several countries in Europe.

“There’s nobody I’d rather be doing this with,” he says. “Nobody in the world.”

Cutting through the (brain) fog

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More than three years after the start of the Covid-19 pandemic, neuropsychologists and neurologists are learning more about one of the scariest symptoms: brain fog. Dr. Gabriel de Erausquin is one of the experts leading the charge. The bespectacled de Erausquin is director of the Laboratory of Brain Development, Modulation, and Repair at The Glenn Biggs Institute of Alzheimer’s and Neurodegenerative Disorders. He also serves as professor of neurology and radiological science in the Joe and Teresa Long School of Medicine at the University of Texas Health San Antonio. Since 2020, de Erausquin has been researching brain fog and its similarities to what happens in the brains of patients with dementia. BrainWise Managing Editor Matt Villano recently sat down with him to learn more.

BrainWise: What is brain fog?

Dr. Gabriel De Erausquin: It is not a medical term, but a phrase people use to describe a range of symptoms including poor concentration, confusion, thinking more slowly than usual, fuzzy thoughts and slower-than-usual short-term memory. In most cases it is temporary or improves over time.

BrainWise: How did your research into this area begin?

Dr. de Erausquin: When the pandemic began, in January and February of 2020, of the things that caught my attention was that people were complaining of impairment in recognizing smells, a symptom that doctors referred to as anosmia. The reason that caught our attention is that anosmia, or lack of ability to recognize smells, is a very common early symptom in several progressive diseases of the brain—specifically Parkinson’s disease, Alzheimer’s disease, and other forms of dementia. That suggested the possibility that the virus was affecting the brain in one way or another. So, we set out to lay the groundwork to collaborate long-term on [researching] the possible consequences of the virus on brain performance and brain function. To do this, we used the platform of a collaborative group within the World Health Organization: Experts Advisory Committee on SCANs. SCAN is an instrument, an assessment instrument, called Schedules of Clinical Assessment in Neuropsychiatry. It’s been around for 30 years, and it’s considered the gold standard as an assessment instrument for neuropsychiatric symptoms, meaning behavioral changes and subjective complaints, including memory complaints, including changes in motor performance and such. This group was meeting in February 2020 in New Delhi. This happened just at the time India was about to close for COVID restrictions, and we had the opportunity to discuss this thing at the very outset and start planning long-term studies. A few months later, the Alzheimer’s Association came on board and brought a significant additional network of people. The consortium exploded, basically, to include something like 100 different institutions in 39 or 40 different countries. That has continued to work with different fluctuating participation over the past several years.

BrainWise: What were the first steps?

Dr. de Erausquin: One of the first questions was, ‘How do you compare?’ Put differently, what do you do to compare cognitive performance across all these different samples in a way that makes sense to include the different levels of cultural, not culture, but rather educational attainment, so different levels of average school participation or literacy, as well as different cultural environments? It’s not the same if you are reading Chinese or Japanese symbols or if you are reading Latin-style characters, or if you’re not reading at all, if your language is spoken, as is the case in the Quechua language, for instance, in the mountains of South America. We had all these different possibilities and we had to come up with recommendations on how to test cognitive change across all these different samples. So that was the outset of the neuropsychological expertise group within the consortium that spent the better part of 2020 and early 2021 working out the consensus. We had some interaction at the time with the International Neuropsychological Society. They had their own vision of how to do things, so it didn’t coalesce into a single effort, but we had some conversations about what they thought was important or ideal. Eventually, the whole thing coalesced into a set of recommendations that were part of a much larger research publication, with the harmonization of the consortia groups on how to test cognitive assessment. A separate grant from the National Academy of Neuropsychology and the Alzheimer’s Association, was intended to create a tool, an app, or a series of apps, that were to be deployed on Android devices, because they are much more prevalent worldwide than iOS devices, and that contained the minimum cognitive assessment that we had all across the world agreed that was necessary for this task. So that was done, that tool is done, is completed, and it’s being tested now.

BrainWise: What are some of the questions you answered after that?

Dr. de Erausquin: In parallel with the deployment of the cognitive assessment on the tablet, we started collecting data, and there are two different efforts that were done in that direction. One of them was a so-called pooled analysis and meta-analysis of cognitive data across the entire consortium that was recently completed, as well. The results were presented in Amsterdam at the Alzheimer’s Association International Conference, and that included a data analysis of cognitive impairment post-COVID in individuals from samples in India, Chile, Argentina, Russia, the UK, Canada, and I’m forgetting a couple of countries. Anyway, it was a large sample, with several thousand people from multiple different cultures. We found there was confirmation, really, of something that we already thought was present, which is a combination of two different types of consequences to COVID. There seems to be two different syndromes. One of them that happens in younger people tends to affect more commonly women than men and, if you will, is less severe. That’s what’s typically described as ‘brain fog.’ This seems to be somewhat reversible or at least less severely chronic. It tends to affect primarily sustained attention, a little bit of the ability to organize tasks, and executive function. And it’s related to lack of stamina, mental stamina, physical stamina on the one hand, and also related to preexisting mood or anxiety symptoms.

This is very different from a second syndrome that is seen primarily in people older, who are 60 years of age, and that is equally frequent in males and females, no distinction there, and that appears to be much closer to what you expect to see in a person with early Alzheimer’s disease. These folks have clear memory impairment, particularly short-term memory impairment, the episodic type. They also hey have much more prominent language impairment. In more severe cases, they have trouble with putting together practical tasks. This second syndrome looks to be very much like an early Alzheimer’s-type of clinical picture. It’s also associated with changes in brain volume. We were not the first ones to report that. That had been reported by the Brain Bank in the UK, but we confirmed it in a larger sample. And we also have found that—perhaps not entirely surprisingly—it’s also affected by your genes. So the risk of having cognitive decline after COVID appears to be inherited, at least in part.

BrainWise: Can you please elaborate on the differences between the two syndromes?

Dr. de Erausquin: The first syndrome is clearly different in that it doesn’t affect memory. It affects primarily attention and concentration and mental stamina, and physical stamina. The two studies that looked at this specifically found that it tends to improve over time. It doesn’t improve on everybody, but it tends to improve over time. And so there is some hint that, at least for a proportion of the people who complain of these symptoms, it is reversible or improving over the first year after the infection. The picture of these younger folks who have it, as I said, are mostly women, younger, often with a history of affective or anxiety symptoms prior to the infection. In some cases, it has looked like this is more akin to the picture of chronic fatigue syndrome, fibromyalgia, postviral encephalomyelitis and other postviral and chronic presentations that are not particularly specific to COVID. This is all very different from the picture of the memory decline that you see in older folks. Those symptoms were clearly Alzheimer’s-like, in the sense that it doesn’t seem to reverse. It seems to be progressive. It doesn’t distinguish male or female and it doesn’t require any preexisting disease or symptoms of neuropsychiatric type as in the case of the brain fog. These folks often don’t have any history of any impairment before. They just present with memory impairment.

BrainWise: What happens in the brain to cause these syndromes?

Dr. de Erausquin: It’s another very important question and one that we don’t have a definitive answer yet. There are several changes in the brain that have been associated with COVID, particularly with acute COVID, and those are mostly vascular, microbleeds, microhemorrhages, and changes in white matter that are consistent with ischemic changes. None of the early data supports the possibility of direct viral effects on the brain. If it did happen at all, it was rare. What seems to have happened is either one of the two things: either the inflammatory changes that were triggered by the virus caused persistent changes in the brain and that’s the so-called vascular hypothesis, or the invasion by the virus of the olfactory bulb, which is the initial brain stop of the olfactory system, was enough to cause what’s called transneuronal or distant effects of the presence of the virus in those neurons. It may be that all that was needed was the presence of the virus in the olfactory bulb for a period, and then several remote effects of that presence followed, changing function in the brain or perhaps structure in the brain in the connections of the olfactory bulb, the so-called extended olfactory network. Both these things seem to happen, but they don’t necessarily represent the same disease process. In fact, they may happen in different people with different susceptibilities and that may account for the fact that we are finding an interaction between memory loss and the genes. To put it differently, it may well be that only susceptible people who have a particular genetic makeup are the ones who got the severe loss of smell and the remote changes in the olfactory network over time and those are the ones who are picking up as Alzheimer’s-like or memory decline in the older folks. Whereas the nonspecific inflammatory postviral changes may be what accounts for the more common syndrome of brain fog in younger folks. This is entirely hypothetical on my part. I don’t have data to support any of what I just said. I mean, accepting directly what I just mentioned, that we know that there is a link between anosmia and memory loss, that we have shown very clearly, and others have. We know that that link is also associated with specific changes in the size of the structures of the brain that are associated with the olfactory function. And we know that there is some form of genetic predisposition that increases the risk of having those problems. And so, we can reasonably hypothesize that it’s one explanation for memory loss. The other, the inflammatory pathway associated with chronic fatigue and brain fog, that’s much less established on the data, much less supported by the data. It is speculative on my part.

BrainWise: What are the next questions you’ll ask? Where does the research go from here?

Dr. de Erasquin: The crucial questions now are: What are the genetic contributions to this? What are the biological mechanisms underlying it? Do we have any targets to prevent it or reverse it? The data we’re collecting include whole-genome sequencing scans of all these folks in very different settings, with and without infection, with documented vaccines and without vaccines, vaccinated before and after having COVID. We know what variants of COVID they were infected by. And we have blood-based biomarkers of neurodegenerative processes, Alzheimer’s-like, and of inflammatory processes. And we have brain imaging, both functional and structural brain imaging data. We will do that longitudinally, so we’ll be able to assess trajectories and assess the impact of all these variables on functional brain imaging, on structural brain imaging, on cognition, of course, and assess the predictive value of the specific gene variations or specific genes on all these things.

NAN and the Alzheimer’s Association partnered in 2021 to offer eight grants totaling $800,000 for research focusing on the impact of COVID-19 — including cognition, behavior and overall functioning — in older adults from health disparity populations. Some of that funding was routed to research cited in this piece. For more information about the grants, click here and here.

The truth about Parkinson’s Disease

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Parkinson’s Disease is a brain disorder that causes unintended or uncontrollable movements, such as shaking, stiffness, and difficulty with balance and coordination. For the better part of the last 30 years, Dr. Alexander Troster has been studying this condition to learn more about what causes it, what happens when people have it, and what treatments seem to work best. Today Dr. Troster is professor of neuropsychology and chair of the Department of Neuropsychology at Barrow Neurological Institute at Dignity Health St. Joseph’s Hospital and Medical Center in Phoenix. His current investigations include the assessment, definition, and neural bases of mild cognitive impairment in Parkinson’s disease, and the evaluation and prediction of neurobehavioral outcomes of deep brain stimulation for a variety of neurological and psychiatric conditions. BrainWise Managing Editor Matt Villano recently sat down with Dr. Troster to learn more about his research and his perspective on Parkinson’s Disease. What follows is an edited transcript of their interview.

BrainWise: How is Parkinson’s Disease diagnosed?

Dr. Troster: There is no one diagnostic test for Parkinson’s Disease. One of the things that’s true of Parkinson’s Disease is that the symptoms with which this disease begins is quite variable. If we look at the most common forms, people either begin with having a tremor, which is probably about two thirds of all cases of Parkinson’s disease, and one third who tend to have more difficulty with walking, slowing and stiffness. What’s important to point out is that before Parkinson’s disease is even diagnosed, this is a disease with a long prodromal period. What that means is that the changes in the brain underlying Parkinson’s disease have been occurring for a long, long time. And the estimates are anywhere from 15 to as long as 30 years before diagnosis.

In general, people have difficulties with movement, they’re slower to move. They may shake, especially at rest. But it’s very hard in the individual case to draw a straight line and say, ‘This is going to be the progression, this is the symptom you’re going to have next.’ Symptoms declare themselves slowly, gradually, and with great variability.

One of the things that’s been noticed is that people with Parkinson’s Disease often have depression, even before they get diagnosed with Parkinson’s Disease. They also tend to have something known as REM sleep behavior disorder. During sleep, the muscles are usually paralyzed and then REM sleep behavior disorder, that paralysis doesn’t occur. When people have dreams, they start to act out their dreams, they talk in their sleep, they might start to thrash, they might start falling out of bed. And these are things that one wants to look for. These are all what we call prodromal things. And one of the things that people also have is a loss of smell, which is very common. When you ask people, they often have before the motor symptoms began a loss of smell many years before that.

BrainWise: Do we know what causes Parkinson’s Disease?

Dr. Troster: No, we don’t. I mean, we can talk about how people with Parkinson’s Disease get a misfold of protein that aggregates in the brain cells, then Lewy bodies and Lewy neurites form, but even with that explanation, you can keep on saying, ‘What causes this?’ The truth is that we don’t really know what causes the disease.

Parkinsonism is not the same as Parkinson’s disease. Parkinsonism is the core symptoms involving, for example, tremor, slowness, stiffness, imbalanced difficulties. But those can be produced by literally well over 100 conditions. And some of those are reversible and some are not. Some are just mimics of Parkinson’s disease. This can be frustrating for patients sometimes because they’ll go in and say, ‘I’ve got a tremor,’ and neurologists often are not going to give a diagnosis of Parkinson’s Disease until some of the other symptoms declare themselves and some of the other tests are done.

BrainWise: Is Parkinson’s Disease congenital?

Dr. Troster: If we think genetically, in terms of Mendelian genetics where either one or both parents have the condition, you’re going to get the condition potentially. There are genes associated with it. One is known as LRRK2, leucine-rich kinase repeating, a protein or what’s also called dardarin. And there’s a gene coating for alpha-synuclein, which is the core protein that accumulates and misfolds and forms Lewy bodies. And there’s two types of genes that are both autosomal dominant genes, meaning if one parent has that and you inherit that gene from that parent, that you’re going to get the disease.

What we don’t know at this point is whether there are minor mutations or polymorphisms either individually or in several forms and number can produce something like Parkinson’s Disease. It is likely that some genetic factors might predispose to environmental factors that can then trigger the disease as well. We know environmental factors like exposure to fertilizers, pesticides, well water, for example, can increase risk for Parkinson’s Disease.

BrainWise: What do people often get wrong about Parkinson’s Disease?

Dr. Alexander Troster: I think some of the misconceptions that people held maybe 10, 15 years ago are no longer the misconceptions they hold now generally. I think the biggest things are still a lack of realization that Parkinson’s disease is more than a movement disorder. Most people still think of it as it affects my movement. Some people mistakenly think it paralyzes them. So, I think over the past 10 years, more and more work has been done on the non-motor symptoms in Parkinson’s disease, and I think patients have become aware of non-motor symptoms as the disease has progressed.

Number two is that Parkinson’s is rapidly progressive. It’s much more [dependent on] when one develops the disease and the symptoms that impact the disease course. People with young onset Parkinson’s very often take a long time to progress. Several studies suggest that if you develop things like a dementia or global cognitive impairment, people with young onset Parkinson’s still develop it in their seventies, just like people tend to with regular onset Parkinson’s disease, for want of a better word. So, I’ve seen plenty of patients with Parkinson’s disease for 25 and 30 years.

I think the other misconception is that there’s little one can do. While it’s true that there’s no treatment or even a disease-modifying therapy at this point, a lot of the symptoms can be treated either pharmacologically or by ancillary therapies like speech therapy, physical therapy, occupational therapy. And more recently there’s been much more effort made at trying to study some methods of cognitive rehabilitation and remediation in patients with Parkinson’s disease.

BrainWise: To what extent do cases of Parkinson’s Disease incorporate dementia? Does the former always lead to the latter?

Dr. Troster: To my knowledge there’s only one good longitudinal study and that’s one from Australia, which I think followed people for up to 40 years. And obviously, that shows that pretty much 95 percent of people with Parkinson’s, if you survive that long, are going to develop a dementia. But of course, many people pass away with secondary things, not necessarily Parkinson’s disease, but for example, aspiration pneumonia, heart disease, regular old age. People pass away and never develop dementia. But yes, obviously most people, if they live long enough, will develop dementia. Far more common than previously thought is what’s known as mild cognitive impairment. Some people have called mild cognitive impairment (MCI) as an intermediate state between normal cognition and dementia. There are cases of mild cognitive impairment that are related to factors such as medications, depression, anxiety and so on. So, if you look at studies of Parkinson’s disease with MCI, probably over three-year period, somewhere between five and 10 percent of cases of MCI revert.

BrainWise: How should a person change their lives after receiving a diagnosis of Parkinson’s Disease?

Dr. Troster: One must start looking for new hobbies, new ways to express one’s creativity. I think it’s very important for people to remain socially engaged. People with Parkinson’s Disease sometimes tend to feel stigmatized or become embarrassed by these symptoms. You also see people with Parkinson’s often try to hide it by putting their hand in their pocket or they sit on their hand. Actor Michael J. Fox himself talked about how long he hid it, and I think it took him eight or nine years before he came out and told people that he had Parkinson’s disease.

I think things are less stigmatizing than they were in the past. I think some people’s reactions to mental health conditions often come from a poor understanding of what the condition is and sometimes a fear or a sense of threat that one may suffer a similar fate. But persons with Parkinson’s Disease are very adapt. We’ve looked at coping strategies. They use coping strategies just like healthy people. They’re quite capable of adapting to the disease, the diagnosis, of keeping on going. Many people with Parkinson’s disease continue to work, they continue to find pleasure in social activities.

I cannot overemphasize, quality of life can be very good in Parkinson’s disease for a long time, despite these changes. And I think people have to hear that.

BrainWise: Once someone is diagnosed with Parkinson’s Disease, is there a uniform course of symptoms?

Dr. Troster: Not really. Not everybody has cognitive impairment—again, look at Michael J. Fox. Cognitive impairment and MCI tend to be especially rare in young onset. Some patients also react differently to medications, develop dyskinesias, or erratic movements, in response to medications sooner, which is unusual. But there are alternative therapies available too, such as deep-brain stimulation.

BrainWise: What is deep-brain stimulation and how can it help?

Dr. Troster: Surgical treatment is usually way down in the armamentarium of treatments. It’s not the first thing one considers. It’s usually when people have side effects from medications or intolerable side effects from them, or the diseases become less responsive, some of the symptoms, or they have complications as they’re from the treatment like dyskinesias or they can’t tolerate doses of medication. Then it’s a good time to consider alternative therapies. Deep-brain stimulation (DBS) is one of those alternatives.

It’s been around 30 years now. The devices have become much smaller, much more sophisticated, so you can steer currents to very small parts of the brain and shape the electrical field with which you’re stimulating the brain. With DBS it becomes easier to control specific symptoms and avoid side effects with the therapy. These devices last [a relatively long time]. Some people choose to have devices with batteries in them that need to be replaced every few years. Some people prefer a rechargeable device, so they don’t have to worry about replacing a battery. Again, it’s not a first line therapy, but it’s a therapy down the road for people who have complications or an unusual course if they’re young and develop some of these symptoms early.

BrainWise: How does this treatment work?

Dr. Troster: It’s pretty much like a pacemaker. The treatment is ongoing, it’s continuous. The device needs to be programmed by a neurologist and the programming tends to take a little more time initially. You’ll have more visits with your neurologist immediately after surgery, probably every four weeks or every two months. Once it’s programmed, you’re probably going to see your neurologist just like every other patient, probably every six to 12 months. The therapeutic benefit lasts a long time. Typically, what people tell you is that the very best you are with medicine is probably the very best you’re going to be with the device. It evens out the effect, so you don’t have the fluctuations. If somebody’s got balance problems or gait disturbance because of balance problems, it’s not going to help for that. It’s not a therapy for everything. People ask whether a person with Parkinson’s disease a candidate for surgery, and I’ve always preferred to turn it the other way around and say, ‘Is this an appropriate therapy for the person with Parkinson’s disease?’

Patients also are very different in their risk tolerance. I’ve seen persons where they see the neurologist and the neurologist says, ‘Well, you’ll have some benefit from DBS.’ And the person says, ‘I don’t care. I want surgery anyway.’ In one example I’ll remember forever, a patient told me, ‘I don’t care. I’m retired. All I want to be able to do is tee up the golf ball.’ My response: ‘Well, who knows,’ sort of jokingly. ‘If it affects your memory, your golf score will get better too because you won’t remember the number of strokes you’ve taken.’

BrainWise: What does the future of Parkinson’s Disease treatment look like?

Dr. Troster: Let me get out the crystal ball here. There’s an amazing amount of research going on in therapies, in terms of molecular biology, genetics, gene therapy, medications, and identifying what causes some of the misfolding of protein. As you know, some advances have lately been made with medications for Alzheimer’s disease. Will there be a similar thing for Parkinson’s disease? One hopes so. I think ancillary therapies are going to continue to get better. [Researchers] have never looked at cognitive rehabilitation in Parkinson’s disease, but now there are people looking at that. [Researchers] also are looking at transcranial stimulation, be that direct current, alternating current or magnetic stimulation. And what’s exciting to some extent is there’s some findings from studies in Italy that suggest with [this treatment] you might make persons more receptive when you do cognitive rehabilitation.

[Other researchers] are trying to find biomarkers. I think that’s one of the things that’s going to be imperative. If we can find these biomarkers and put them together with other markers, we can predict what the course of the disease is going to be. Then we can determine what treatment needs to be given. I think in future, maybe five or 10 years from now, doctors are going to say, ‘We need to treat you fairly aggressively; this is going to be a progressive quick form of Parkinson’s,’ or, ‘This is going to be relatively benign. You’re going to develop this at that stage, and we’ll treat you at that time for this [one] symptom.’ So I think with treatment tailored for individual symptoms rather than trying to hit all symptoms with one drug or two drugs, that will be the way things go down the road.

BrainWise: Finally, Dr. Troster, what’s the next big research question for you?

Dr. Troster: The big question is, ‘Can we predict who’s going to develop dementia with Parkinson’s disease and how quickly?’ Because these are the folks we really want to spend more time on. We want to repair families, make these changes earlier, and hopefully predict these things sooner. And I’m not hopeful that our neuropsychological tests are necessarily the best for this right now. About 25 years ago, when I started focusing on this, a Parkinson’s Disease expert who will remain nameless said to me, ‘Why are you doing neuropsychology in Parkinson’s disease? It’s a movement disorder.’ That’s a big [hurdle to overcome.]

Non-motor symptoms are the big challenge in Parkinson’s Disease today. These are things that lead to caregiver burden. These are the things that lead to institutionalization, and loss of independence. I think we’ve made huge strides in the last 10 years. I think we also have a long way to go. We’ve come to realize a lot of what some of the issues are, whether they’re impulsive and compulsive behaviors that people can develop, cognitive changes, depression, anxiety, psychosis, other non-motor features, like some patients develop pain, sleep disturbances. How do we cope with those? How do we best treat those? And I think we’ve come to recognize them at least, and able to diagnose them a little better. Now what we have to do is get better treatments for these things.

What Tony Bennett taught us about life with dementia

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It was difficult to find people who didn’t like Tony Bennett.

Sure, they appreciated his mellifluous voice—the crooner entertained us for more than 70 of his 96 years. But what stood out most about Bennett was his charisma and his zest for life.

Naturally, then, his death earlier this month sent shockwaves through several different communities. Considering that the New York native had been living with Alzheimer’s Disease since his diagnosis in 2016, the neuropsychology community was one of those that mourned him the most.

Bennett stood out to neuropsychologists for how he managed to live with Alzheimer’s Disease, the most common form of age-related dementia. At a time when Alzheimer’s was being stigmatized, Bennett and his family leaned into the diagnosis, acknowledging the truth and forging ahead with life, music, and whatever else made Bennett happy — until he simply couldn’t do it anymore.

(For example, Bennett collaborated with Lada Gaga on the “Love for Sale” album in 2021.)

An AARP magazine article published in 2021 quoted Bennett’s doctor as saying the singer should be seen as an inspiration to all families with loved ones who are diagnosed with Alzheimer’s Disease late in life.

“He’s doing so many things at 94 that so many people without dementia can’t do,” said Dr. Gayatri Devi, the neurologist who diagnosed Bennett. “He really is the symbol of hope for someone with a cognitive disorder.”

More recently, Dr. Bill Perry, executive director of the National Academy of Neuropsychology (NAN), agreed.

In the days following Bennett’s death, Perry waxed poetic about what the singer meant to the neuropsychologists and those who study brain health.

“One of the amazing things about Tony Bennett was his willingness to be open about his disease,” said Perry, who also is a professor in the department of psychiatry at the University of California, San Diego. “When people of fame like Mr. Bennett are willing to make their diagnosis and experience public, it helps to diminish the stigma that is associated with having a diagnosis of dementia.”

Neuropsychologists and neurologists say a strong support system of loved ones is key to helping patients with Alzheimer’s Disease thrive. Devi, Bennett’s doctor, told AARP this was the case with Bennett, as well.

Devi told AARP that in addition to Bennett taking the standard Alzheimer’s medications (cholinesterase inhibitors that regulate the concentration of the brain’s chemical messengers for normal memory function) and his regimen of diet and exercise, the singer’s continued high functioning and well-being was directly attributable to his strong family support.

“I [was] humbled by the level of devotion,” Devi was quoted as saying. She added that constant interaction with his wife and kids helped stimulate Bennett’s brain, which undoubtedly prolonged his life.

Bennett’s experience with dementia can and should be a lesson for all of us—when one of our loved ones is diagnosed with Alzheimer’s Disease, we must show up for them as we did before their diagnosis and put them in a position to thrive in their final years.

We’ll always remember Tony Bennett’s voice and music. We must remember his heart and spirit, too.

Record number of Alzheimer’s drugs in development in 2023

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A record-setting number of drugs for Alzheimer’s Disease are in the development pipeline this year—a clear sign that pharmaceutical companies are trying now more than ever to devise potentially viable strategies to treat the condition.

As of January 1, 2023, there were 187 trials assessing 141 unique treatments for AD. Disease-modifying therapies were the most common drugs, comprising 79 percent of drugs in trials.

Populating all current trials will require more than 57,000 participants.

This data was published earlier this year in Alzheimer’s & Dementia Translational Research & Clinical Interventions, which publishes an annual article about current Alzheimer’s Disease drugs in trial. The piece was authored by several researchers led by Dr. Jeffrey Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.

Data from 2023 represents a significant uptick from data the same publication reported in 2022. Last year, as of January 25, 2022, there were 143 agents in 172 clinical trials for Alzheimer’s Disease.

Methodology for these studies was varied.

Study authors searched the governmental website clinicaltrials.gov, where are all clinical trials conducted in the United States must be registered. Authors used artificial intelligence and machine learning to ensure comprehensive detection and characterization of trials and drugs in development.

Study authors also used the Common Alzheimer’s Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline.

New drugs must successfully complete a three-phase clinical trial process before being approved for use by the Food and Drug Administration (FDA); they must perform well enough in each phase to progress to the next one. Preclinical studies in laboratories establish a scientific basis for believing a drug is reasonably safe and may be effective.

Phase I trials, the first stage of human testing, typically involve fewer than 100 volunteers and look at the risks and side effects of a drug. Participants at this phase are often healthy volunteers.

Phase II trials enroll up to a few hundred volunteers. These studies provide further information about safety and help to determine the best dosage of a drug, and are generally too small to provide clear evidence about a treatment’s benefit.

Phase III trials enroll several hundred to thousands of volunteers, often at multiple study sites worldwide. They provide the chief evidence for safety and effectiveness that the FDA will consider in deciding whether to approve a drug. No Alzheimer’s Disease drugs can be approved unless they pass all three phases.

Typically, as Dr. Cummings told BrainWise in a Q&A earlier this summer, there is a high rate of failure in Alzheimer’s Disease drug development with 99% of trials showing no drug-placebo difference.

Still the Alzheimer’s Disease drug development pipeline is leading to new therapies.

After a 17-year hiatus in drug approvals, two agents—aducanumab and lecanemab—have entered the market since 2021. Other drugs have shown promise in Phase III testing. Dr. Cummings said this data indicates there is hope for Alzheimer’s Disease patients.

Alzheimer’s Disease is increasing at an alarming pace as populations age. According to the Alzheimer’s Association, there are an estimated 6.2 million individuals with Alzheimer’s Disease in the United States and an estimated 50 million individuals with Alzheimer’s Disease globally. These populations will grow to 12.7 million and 150 million in the United States and globally, respectively, by 2050.

The future of Alzheimer’s Disease drugs

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Few people in the world know more than Dr. Jeffrey Cummings about treating Alzheimer’s Disease. Dr. Cummings is a research professor in the department of brain health at the University of Nevada, Las Vegas. He’s also director of the Chambers-Grundy Center for Transformative Neuroscience at UNLV. Every year Dr. Cummings publishes a report about the number of trials for new drugs to treat Alzheimer’s Disease. This means he has his finger on the pulse of Alzheimer’s Disease treatment approaches. BrainWise Contributing Editor Matt Villano recently sat down with Dr. Cummings to discuss 2023 data and the future of Alzheimer’s Disease treatment overall. This transcript of their conversation has been edited for clarity.

BrainWise: When we look at the landscape of Alzheimer’s drugs treatments today, what would you say characterizes a lot of them and what specifically are these medications addressing?

Dr. Jeffrey Cummings: We’re in an enormously fast-moving portion of Alzheimer’s disease research and therapeutic development. From 2003 to 2020 with no approvals of new medications. During that time, the pharmaceutical industry by itself spent $40 billion on Alzheimer’s disease clinical trials. In 2021, we had the approval of aducanumab, and then in 2023 the approval of lecanemab, both of those by accelerated pathways. Now, we think that within the next probably two months, we will have standard approval of lecanemab and likely standard approval of donanemab.

Soon there will be three monoclonal antibodies on the market. A critical step in that is the review of them to determine whether they will be reimbursed, because people will take the medication only if it’s reimbursed, and they can benefit from the medication only if they take it. We must establish that link in order for Alzheimer’s patients with early Alzheimer’s disease to benefit from this research advance. To emphasize a few of those areas, these are complicated drugs, monoclonal antibodies administered intravenously, and with a side effect called ARIA that must be carefully monitored and managed. On the other hand, they are the first disease-modifying therapies for Alzheimer’s disease and almost the first disease-modifying therapies for any neurodegenerative disease. Only ALS has some disease-modifying agents, nothing for Parkinson’s disease, frontotemporal dementia, any of the other late onset neurodegenerative diseases. This is a breakthrough. It’s truly a breakthrough, because it’s turning a corner on disease modification and our ability to impact the underlying biology of the processes that lead to neurodegeneration.

The clinical benefit is modest. There’s been some criticism about this. It’s about 30% slowing of cognition, about 40 percent slowing of function. I think that’s fantastic. If I had MCI, which lasts about three years, and I could make my cognitive integrity last another year during that period before I became fully demented, I would want it. I think that’s the human question that is worth asking. What is the value of human cognition towards the end of life? I find these worthwhile drugs, but I acknowledge the complexity that they bring, for sure.

I regard them also as a preliminary, almost proof-of-concept, advance. They show us that amyloid is a reasonable target. They’re not the drugs that we want ultimately, right? We want drugs that are more efficacious. We would like them to be more convenient. We would like them to be safer. All those things are goals to be realized in the next steps in therapeutics.

There are other drugs in the pipeline, some close to coming to the end of their trials. They have reasonable hypotheses. We have evidence for these monoclonal antibody approaches. We also have, I think, pretty strong evidence for the anti-tau ASO, a drug which must be administered directly into the spinal canal. The effect of that [in trials has been] unbelievable. Again, I see real excitement in the field all around our ability to manipulate the biology.

BrainWise: You just raised a fascinating ethical question. What is the value of human cognition later in life? How do you think a family should address that when a loved one has Alzheimer’s Disease?

Dr. Cummings: This is a question I want my patients to answer. I don’t want Medicare to answer it for them. I want them to be able to say, ‘Yes, I want to go in for an infusion every other week with lecanemab,’ or, ‘Yes, I want to have those MRIs that are required to make sure that I don’t get ARIA,’ or ‘I’m 92 and I want to live out my life now without these medical complications.’ I think those are all defensible positions and I want my patients to be able to make them.

One of the things I am trying to help achieve is the availability of the drugs so that my patients can make educated choices. We’re going to have to educate patients and caregivers and the world about these drugs and hopefully we’re going to get simpler. There are already subcutaneous equivalents in clinical trials and there are already blood tests that look pretty good in terms of being able to replace the PET scan and the lumbar puncture to establish the diagnosis. But once we can identify the patient with a blood test and treat them with a subcutaneous injection, we’re in a different world of the inconvenience that these drugs currently represent.

That’s coming fast. We need to accept that we don’t know what the future will bring, so we need to deal with what we have now. But if you had to forecast, how long will we be here in this space? I think we’d say a short period of time, because the subcutaneous injections look very good, and the blood biomarkers look very good.

BrainWise: What are the most important questions for drug researchers to be asking at this point, as we look to future development?

Dr. Cummings: I would say we’re looking forward to combination therapies. Improvement of 30 or 40 percent is not enough. So, what do we want? Well, we would like essentially to arrest the disease progression. We’d like a combination of therapies that would come close to that. We also want to improve cognition. We want to restore them to as close to a normal level of function as we can. Only 11 percent of the pipeline is currently devoted to cognitive enhancers. Those are drugs that would improve cognition. And 78 percent of the pipeline is currently devoted to disease-modifying therapies, drugs that would slow the progression. So, one of the things I’d like to bring back into the drug development world is more emphasis on cognitive enhancement.

Other questions pertain to how we’re approaching this. Recruitment is horribly slow. It’s the major reason that we’re not getting drugs through each phase quickly enough. The diversity of recruitment is terrible. We’re not reaching diverse populations and we have no idea whether these drugs are equally efficacious across racial and ethnic groups, yet we’re going to sell them across racial and ethnic groups.

BrainWise: To what extent are there currently trials in place that incorporate a more diverse subject group?

Dr. Cummings: One example is the Global Alzheimer Platform, which did a biomarker trial. They achieved, I think, 22 percent racial and ethnic minority representation in that study. That’s pretty good. I think we’re kind of pretending right now that we’re going to have an answer regarding treatment in minorities if we include a representative number [of minorities in trials]. We will not.

BrainWise: What’s the current landscape of trials?

Dr. Cummings: This year—the 2023 data just came out—we had 178 trials and 141 unique agents in clinical trials on the index date of the study. Most of them are not viable. When we last calculated, there was a 99 percent failure rate of Alzheimer’s disease therapeutics. I think it’s less severe than that now but I’m sure it’s at least 80 percent. Most of them still will not be viable. One of the correctable reasons that drugs fail is because they’re in poorly designed trials. We want to make sure that when a drug fails, it’s because the drug didn’t work, not because the trial didn’t test it adequately. This is a solvable problem over here. We can make those trials be great. We should require it. We can’t predict which target will work, that’s why we have a whole bunch of targets.

BrainWise: What trends are you seeing?

Dr. Cummings: More trials; the 2022 numbers weren’t as high. Another trend that is obvious is that the type of drug is changing. A biologic is a big molecule that must be given intravenously or subcutaneously or intrathecally (which means, into the spinal canal). Those are all called biologics. The drugs that are given by mouth are called small molecules. What you see in the pipeline over the past five years is the growth of the biologics. It’s interesting. It’s gone from 40 in the pipeline to 60 in the pipeline, which is about a third of the pipeline.

This is important because that’s what the doctor is going to offer the patient. It also means the doctors must begin thinking about what their practices are going to look like. They’re going to have to have infusion chairs, they’re going to have to anticipate subcutaneous administration. Alzheimer’s Disease treatment likely will become much more like cancer therapy. Practice patterns are going to have to change. Healthcare systems are going to have to change. And that’s part of the stress that we are going through right now: How do we change a whole system when we get an unprecedented compound that is effective but makes [real] demands on the system?

One position that I’m taking in some of the things I write is that this is the first step. The march of science is no doubt going to yield more medications, and we [must] have social and healthcare systems that can absorb the advances in science. We haven’t had much success before, so we haven’t had to do much of that before. But we should see this almost like a test case. How do we begin thinking about having a system which is sufficiently flexible; [a system into which] we can introduce new medications without there being a lot of hurdles? By the way, the pharmaceutical companies must be partners here. If they make the prices very high, that’s just another hurdle. But if this is a kind of collaborative arrangement so that we can get these drugs in without too much cost, then the system is likely to have the flexibility to be able to do it.

BrainWise: Tactically, what aspects of the landscape of the brain will be the targets of the next generation of Alzheimer’s Disease drugs?

Dr. Cummings: I think amyloid will continue to be a target. Tau looks like a good target. The two most active areas in the pipeline are inflammation and synaptic function. We’re going to see a lot of emphasis on trying to decrease the inflammatory aspect of Alzheimer’s disease. There are roughly 20 drugs against inflammation in the pipeline right now. No two of them have the same target within inflammation. Is one of these more manipulable than another, in a way that we can see a therapeutic benefit or early on a biomarker benefit? Is there a combination that looks like it might work together because both have small effects?

The fact that we have so many targets within a given process is going to be highly informative. The same is true of the synaptic function. Of the roughly 15 drugs addressing the synapse, only two have the same mechanism, so it is interesting to see how diversified the mechanisms are within a single target area.

BrainWise: Five years from now, what do you think Alzheimer’s Disease treatment looks like?

Dr. Cummings: It’ll still be dominated by biologics, but I do believe [some treatments will] be given subcutaneously or maybe at longer intervals. We might be able to extend this so that we could give a drug, say, every three months after an initiation period where it’s given every month. That’d be a great outcome so that the patient doesn’t have a lifelong commitment to infusions every other week or every month as they are now, depending on the drug.

With donanemab, when [patients] get the amyloid levels to undetectable, they stop. That’s interesting because, of course, that’s a lot cheaper drug than the drug that must be given continuously. Already, we’re seeing vastly different strategies within this therapeutic category. So, I think we will continue with biologics. I also think these blood tests are going to be so great that we’re going to be able to use them very effectively, both to choose who needs the therapy, to follow that therapy, and maybe when therapy is interrupted, to decide when to introduce it. I think the blood tests are going to help us in a whole variety of ways.

BrainWise: Where does stem-cell development fit into this overall puzzle?

Dr. Cummings: There’s a lot of excitement about stem cells. There are six stem cell trials in play right now. Five years is a short time horizon for that, because the FDA is very conservative in terms of stem cell trials. Often, they [administer] stem cells and then watch for a year to see what happens. [It ends up being] 18 months or two years to recruit the trial, and then it’s a year after the last patient in before you get the last patient out. Now, you’re talking about three years already.

I don’t think we’ll have stem cell therapy [for this] figured out in five years, but I think that’s a worthy pathway to keep working on. Can we make sure they’re safe? That they do what they’re supposed to do once we introduce them into the body? What’s the magnitude of the response and what’s the durability of the response? These are the things that must be answered, and they’ll be answered, I think, more slowly for stem cells than they are for biologics or small molecules, because the trials are more difficult to do.

BrainWise: How likely is it that we’ll see combinations of different treatments?

Dr. Cummings: I think it’s very likely, even necessary. I think manipulating one target is almost certainly not going to be enough to halt or seriously slow complex disease. At the same time, combinations are tough, because a company [would need] to have two agents at the same level that could be put into the same trial, and they almost never have that. [The way it is] now, you got to have one company with one agent and another company with the other agent, and those two companies [must] work together. These are just operational complexities that keep us from doing what we want to do.

The trials are hard, and the developmental process is hard, but we absolutely must do it. This is where, I think, federal funding is critical, because you could get two repurposed agents and put them in the same trial at the same time, and at least see whether manipulating those two pathways looks beneficial. If so, you have a whole range of ways to exploit it. But there are complexities that you don’t ordinarily think of, like a company must have two drugs in order to do the trial of combinations, and it’s a rare event in the company. They usually have one asset that they’re advancing in Alzheimer’s disease and then a bunch more that they’re advancing in cancer, so they don’t have two assets that they can put into the same trial.

BrainWise: As we look to the distant future, to what extent do you envision super drugs that might be able to treat Alzheimer’s Disease and other forms of dementia?

Dr. Cummings: What I want is the AIDS discovery. You have the virus, put your person on combination therapy, and they’re able to live, really, without manifestations of the infection for many years. Magic Johnson, right? The classical example of this. That’s what we want. Do your blood test every year. When your PTAL 217 starts to rise, you’re getting amyloid in the brain. You get put on a combination therapy and you stay on that for the rest of your life, and you follow your PTAL 217 to know whether you have ameliorated the acceleration of the neuronal processes in the brain. That’s a kind of future scenario that, I think, is realistic. I think that could be done and looking forward to having it be done.

BrainWise: What other mysteries do we need to solve about Alzheimer’s Disease?

Dr. Cummings: There’s a part of Alzheimer’s Disease that is driven by aging, and aging is pretty hard to fix. I’m not forecasting a cure, but I do foresee a time when we could prevent the disease through early detection or maybe through risk stratification of people in their fifties. Amyloid starts in the fifties, and then people become symptomatic 20 years later in their seventies. We could start testing very early. By then, maybe we will have small molecules that could be taken, so it would not be an inconvenience and we could prevent the onset of illness.

BrainWise: What are the next big questions you’ll be asking in your research?

Dr. Cummings: How can we accelerate biomarkers to allow us to do great drug development? That’s a huge one. Because it turns out that biomarkers have been the key to our success, That’s why we have monoclonal antibodies. We also have what’s called the Amyloid Tau Neurodegeneration framework, or ATN. We have biomarkers for all three of those. We need more biomarkers so we can be more informed about the impact of therapy and who should be on therapy. We also need biomarkers of health. The biomarker expansion is critical, both for the disease and also to begin to understand the biomarkers that would signal good health in individuals, because it’s ultimately some sort of algebra between the brain health and the brain disease that determines who becomes symptomatic.

BrainWise: What do you want people to know about Alzheimer’s Disease?

Dr. Cummings: If I had to simplify the message, I would say great progress is being made and hope is there. We’re going to be able to help people. We’re going to see who needs help early on. We’re going to keep people at a more dignified level of function during their aging years.

At the same time, while there has been a good increase in funding for Alzheimer’s disease, we need more. Alzheimer’s disease has a greater negative impact now in the country than cancer does, and yet we’re far behind funding in terms of cancer. We need money because we need to grow more centers. We need more outreach to minority communities. We need more outreach to rural communities. We’ve got to get everybody on this wagon. We’ve got to make sure we’re helping everybody, and that costs a lot of money.

What to consider after a loved one receives a diagnosis of dementia

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The patients and families in my clinic are often referred to me for this key question:  “Do I have dementia?”  

Family members may sense that something has changed for their loved one. Patients may know something is different but may not be fully aware of the problems and changes they are experiencing. This can lead to a great deal of fear around the potential diagnosis and what the future may hold after that diagnosis. It also highlights the importance of thorough evaluation and clear communication around assessment findings. Dementia is a familiar term to most people, even though it is often used incorrectly. The word, “dementia,” refers to the depth and breadth of cognitive and practical problems.  However, the term “dementia” does not speak to what is causing those problems. The underlying cause of dementia can be any number of things, including Alzheimer’s, Parkinson’s, stroke, and many more. Despite the cause, informing someone that they have signs of dementia—of any kind—is often heartbreaking news for patients and their families. It’s also difficult for the doctors who deliver that news.  This is why many doctors hesitate to share the diagnosis or defer the responsibility to specialists.

This is where I come in as a neuropsychologist. Breaking that news is one of the single most difficult things that I do in my clinic, and yet I do it often. In helping patients and families digest this news, I’ve come to see it as an honor to walk patients and families through the practical first steps of being introduced to the realities of the diagnosis.

To help make this happen, I ask families to prepare for the worst-case scenario and live for the best case.

I encourage families to prepare for problems ahead of time instead of responding when the problems are too big to ignore.  Emotions can take over and cloud judgment too much in those times.  First, I ask families to think through their loved one’s practical needs.  How much practical trouble is the patient having in their day-to-day life?  What help do they need now?  How can they prepare for, if, or when that trouble gets worse?  I ask them to be familiar with their loved one’s daily routine and their usual needs.  A big part of this is familiarizing themselves with their loved one’s medication regimen and financial situation. It’s ideal if families can be comfortable with these needs before their loved one needs help, but it’s never too late to start. 

I also ask families to update their home emergency plan, to make sure their loved one is safe in case of a house fire or natural disaster, for instance.  These situations can be doubly hard for a person with any kind of cognitive problem. 

Some of the questions to think about are harder.  I ask them to think long and hard about driving—how much longer can the person who has received a dementia diagnosis keep driving safely?  The answer is different for every person. The gold-standard driving skills test is a practical behind-the-wheel test with an occupational therapist who is specially trained to examine driving skills.  Neuropsychological evaluation can also assess some skills that are important to driving, such as how fast the brain can process information and how easy it is to juggle attention. Sometimes, scaling back driving to good weather conditions, within a few miles from home, with little to no distraction in the car might be the most appropriate choice, and sometimes, no driving altogether is the better option.

I ask families to consider their plans for their loved one’s long-term care.  When will they need to ask for help in caring for their loved one?  What might that help look like?  For different families, and at different times for the same family, it might mean help from friends and neighbors, scheduled respite care from a professional caregiver, live-in help, or nursing home placement.  Considering all options ahead of time can be a great comfort when and if a patient needs more hands-on care than their loved ones can give alone.  The financial aspect is also important to consider. Do they have insurance policies or benefits for long-term care?  They may also want to contact an expert in elder law for advice on how to protect their loved one’s assets if their condition worsens and long-term nursing facility care is needed. 

I ask families to make sure that their loved one has Advance Directives for Health Care (this is also known as a Living Will) and Power of Attorney for health care, legal decisions, and finances.  Many states, including my home state of Kentucky, have premade documents to cover the basics of a living will and health care power of attorney.  Families should be aware that power of attorney for health care does not apply to finances and legal issues, so asking a trusted attorney for guidance on those issues can be important.  Once the documents are done, keeping multiple copies of them in a safe place with other important papers, as well as on file at the patient’s primary doctor’s office, can give a lot of peace of mind.

Beyond these important issues, I ask loved ones to think about what I call The Big 5.  These are five key parts of brain health for anyone and need special attention for families dealing with a diagnosis like dementia. (Click here to download a PDF of the infographic below.)

An infographic about five important issues to consider after a loved one has been diagnosed with dementia.

Head injury prevention

Falls are bad for older adults in just about any condition; for those with dementia, they can speed up the onset.  When elders fall and hit their heads, it can cause bleeding on the brain.  I advise family members of my patients to always protect the patient’s head. This can be as simple as making sure pathways are clear and shoes fit well.  Be aware of little pets that love to be underfoot.  Put bars in the bathroom and on the stairs.  Make sure area rugs don’t curl up and cause hazards.  Sometimes, an Occupational Therapist can do an in-home evaluation to give pointers for safety. 

Heart health

In general:  Anything that’s good for your heart is good for your brain.  Your heart is pumping about 20 percent of your blood straight to your brain every time your heart beats—a large closed-loop system of pipes connects them. If something goes wrong with a patient’s heart, it increases the chances that something can go wrong upstream in the brain. This means it’s important to stay on top of things like blood pressure and sleep apnea. It also means following a heart healthy diet, like the MIND diet, avoiding processed foods, and getting reasonable, regular exercise.  One of the most important keys to heart health is well-known:  No smoking!  Quitting smoking, or never starting, is one of the single most important things we can do for our brain health and for the rest of our bodies. 

Sleep

I tell my patients to treat sleep like it is sacred.  When we sleep, our brains go through their regularly scheduled maintenance programs. It’s like taking your car in for an oil change and transmission service —especially during REM sleep and deep sleep.  We all need this sleep, but people with dementia might need it even more.  Some new research says that deep sleep might help slow down the progress of the disease.  This shows why sleep apnea can be such a problem.  Sleep apnea disturbs our sleep cycles, sometime keeping us from getting enough REM and deep sleep.  It also rations the oxygen in our brains, which can make thinking problems worse.  Sleep apnea can also increase the chances of heart attack and stroke, which can damage the brain even more.  If you have sleep apnea, good treatment is important. 

Cognitive activity

Especially as we age, we must keep thinking and using our brains.  Our brains are made to learn, especially in the real world, engaging in the activities of real life.  Read the book. Visit a new place. Try a new food. Learn a new hobby.  Meet some new people. Our brains love all that stuff. Sudoku and crossword puzzles are great, so long as they are engaging for someone’s brain.

Stay Connected

There are all kinds of research proving that loneliness is toxic to our physical bodies. Isolation is not good for us. I always tell loved ones and family members of my patients: Now is the time to double down on relationship.  Check in on them, make sure they have every opportunity to connect with friends and family to maintain their important relationships and connections.  This is especially important if a patient cannot drive:  Those folks too often get cut off from the outside world.  While doing this, it’s also important to make sure the patient doesn’t get overwhelmed.  Because of this, families might need to rethink how best to offer those connections.  They might need to rethink how to manage family traditions, like big holiday dinners.  Again, talking about these issues ahead of time can help immensely. 

Remember when I said that I want my patients to live joyfully, no matter their diagnosis? I know none of this sounds all that joyful.  But remember, I want to help these families prepare for the worst and live for the best.  Because of this, I also ask them to go have fun.  Especially if the diagnosis comes early, I tell them: Take the trip, do the experience, get after it. If there is anything you’ve dreamed about doing, do it.  Spend time together and love one another with intention and dedication.  Do this, and some of your best memories may be ahead of you, not behind you. 

Click here to download a PDF of The Big 5 infographic.

For more information about elder law, check out the National Elder Law Foundation and the National Academy of Elder Law Attorneys.

Setting the record straight about assessments

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In an article published in The Wall Street Journal last month, a retired physician named Dr. Seth Stern reported that he began experiencing cognitive deficits at age 59. Having dementia running in his family, he was attuned to the possibility that he may be experiencing the initial signs of cognitive decline.

The article (which is behind a paywall) goes on to state that, “It is nearly impossible for people such as Dr. Seth Stern to be diagnosed with dementia because neurocognitive testing is normed to a 12th-grade education level.” This statement is misleading: While it is true that highly educated people can present challenges in detecting impairment, neuropsychologists are skilled in using cognitive tests that have been designed to detect decline in people with greater than a 12th grade education (i.e., tests are normed for highly educated people).

Let’s unpack this a little further.

Yes, it is true that the detection of cognitive impairment in high-functioning older adults is often difficult. This is in part because high-functioning persons tend to have increased cognitive capacity—also known as “cognitive reserve.”

Cognitive reserve can result in later expression of clinical symptoms. Dr. Yaakov Stern, a professor of neuropsychology at Columbia University, defined it as, “the ability to optimize or maximize performance through differential recruitment of brain networks, which perhaps reflect the use of alternate cognitive strategies.”

Importantly, high-functioning individuals may maintain a high level of verbal skills, which can serve to mask any cognitive impairments.

The WSJ article also suggests that primary care doctors are often reluctant to diagnose dementia early on for a variety of reasons, among them a concern that “nothing can be done.” This may have been true in the past, but presently there are several effective treatments for dementia when detected early, and several other treatments under trial right now.

(Current data on Alzheimer’s drugs under trial in 2023 was released earlier this month; you can access 2022 data here.)

Given the challenges in detecting cognitive impairment in highly educated people, neuropsychologists can serve an important function. Skilled in detecting cognitive deficits, neuropsychologists identify and characterize impaired cognitive functions as well as those functions that have been spared. Furthermore, neuropsychologists work closely with other medical specialists to determine underlying neuropathology and to predict clinical outcomes.

The role of neuropsychology is likely to be elevated with the introduction of medications such as Aducanumab, which can be a treatment option for early-stage dementia and result in people having increased time to participate independently in activities of daily living.

Expanding healthcare teams to include primary care physicians, geriatric specialists, neurologists, and neuropsychologists will help to initiate interventions that may delay progress of cognitive disorders. Providing more comprehensive approach also will provide an opportunity for patients and families to collectively participate in making care decisions and health care plans.

Dr. Perry is Executive Director of NAN. 

Understanding Conditions of Aging, Frontotemporal Dementia

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When actor Bruce Willis was diagnosed with Frontotemporal Dementia (FTD) earlier this year, it thrust the degenerative neurological condition into the national spotlight. Many people learned about FTD for the first time. The stories served as a sobering reminder of how our brains change as we age. Dr. Andrew Budson, chief of cognitive and behavioral neurology and director of the Center for Translational Cognitive Neuroscience at the Veterans Affairs Boston Healthcare System, is an expert on that subject. Dr. Budson has co-authored several books, including a new work titled, “Seven Steps to Managing Your Aging Memory: What’s Normal, What’s Not, and What to Do About It.”  BrainWise managing editor Matt Villano recently sat down with Dr. Budson to discuss the conditions of aging and how we can better understand what happens to our brains as we mature. What follows is an edited transcript of their conversation.

BrainWise: What are the most common misconceptions about Frontotemporal Dementia (FTD) and what separates it from dementia more generally?

Dr. Budson: Dementia is a general term that we use when people’s thinking and memory have gone downhill and deteriorated to the point that it interferes with day-to-day function. Alzheimer’s disease is one type or one cause of dementia and frontotemporal dementia, abbreviated as FTD, is another type or cause of dementia. FTD basically comes in two types: language variants and behavior variants. The language variants are off in their own world; we now call them primary progressive aphasias. When Bruce Willis was initially diagnosed with aphasia, I would say what that means is he had primary progressive aphasia. The causes of aphasia could be a stroke, a brain tumor, a traumatic brain injury, or it could be a neurodegenerative disease like a frontotemporal dementia variant. FTD affects the temporal lobes. That’s why it tends to affect language, because our store of knowledge and our ability to speak are both close to the temporal lobes. The temporal lobe is our storehouse of words. Names of people, names of animals, names of tools—they’re all in there. People with disruptions to those parts of the temporal lobes may not recognize a word and forget what something is all together. I had one patient with FTD, and this person had lost the words for many body parts. I asked him, ‘What’s an elbow?’ And he was like, “Elbow. I know the word elbow, but I don’t know what it means.” This person also didn’t know what a knee was. Or a foot. It was very interesting.

BrainWise: So with primary progressive aphasia, the word itself doesn’t disappear, but rather the connection between the word and the definition?

Dr. Budson: That’s right. People can lose what a fork is for or something like that. They may be like Ariel in ‘The Little Mermaid,’ who comes across a fork and thinks it’s used to twirl her hair or something like that. It’s like if you grew up in a culture that just didn’t have forks, so you’d never seen one before. You had no idea what to do with it. Those sorts of things can happen. There are other types of language variants of frontotemporal dementia. People can have trouble getting the words out. They may know exactly what they want to say. They haven’t lost the words, but they have trouble getting the words out.

Behavioral variant frontotemporal dementia is when the frontal lobe is deteriorating, and patients began struggling with everyday life. In some cases, patients will have trouble completing complicate tasks or they’ll just become apathetic—they’ll just sit there like a bump on a log. In these cases, the deterioration is impacting the top and outer part of the frontal lobe, also known as the dorsolateral. In cases where the damage to the frontal lobe is on the bottom or the middle—the ventral medial—people become uninhibited, and they can’t control their urges. They may act or say or do whatever comes to mind without any filter. Of course, this can lead to aggression if the person’s asked to do something they don’t want to do. All these situations are difficult to endure as a patient and difficult to watch as a family member. They’re all variations of FTD.

BrainWise: So back to the Willis case for a moment. Is it safe to say that aphasia is a symptom of the language variant of FTD, or is aphasia its own genre of FTD?

Dr. Budson: It’s almost both, and the reason I say it like that is when people first present, when they first come to the doctor with problems speaking that have come on gradually and an evaluation is done, that would always include an MRI scan and some type of language cognitive testing. If they’re not having any behavior problems, we would assume it is primary progressive aphasia. Now, as the frontotemporal dementia progresses, so what happens is more and more of the brain becomes involved. Basically, what I’m saying is that people who start with primary progressive aphasia, especially if it’s due to frontotemporal dementia, will experience spread and will begin to have behavior problems too.

I have never met Bruce Willis. I have certainly never examined him, but I would speculate that because we are first told he had aphasia, which I thought from the start must be primary progressive aphasia. Then later we’re told he has FTD, he has frontotemporal dementia. My speculation is that it was always a form of frontotemporal dementia that began with the temporal lobes being involved, causing language problems. It then spread to the frontal lobes causing behavior problems as well, and that’s when we heard on the news it was FTD.

BrainWise: How common is FTD? How prevalent is this in a population of people over age 65?

Dr. Budson: In a population of 65-plus, I would estimate it’s probably somewhere around 50 times less common than Alzheimer’s.

BrainWise: And what is that number?

Dr. Budson: By the time people reach the age of 85, approximately 40% of those 85 and older have Alzheimer’s. The dementias do become more common as people get older. One of the interesting things about frontotemporal dementia is although approximately a quarter of patients do present above age 65, three-quarters of them present younger than age 65. It’s a more common cause of dementia in younger people. The ages of patients there usually fall into the 45 to 65 range.

BrainWise: Why is there a link between age and brain development over time and memory loss?

Dr. Budson: We don’t fully know the answer as to why these different disorders of thinking and memory develop. With Alzheimer’s, there are two collections of proteins. One of them is outside the cell and it’s called amyloid or sometimes beta-amyloid. Then there’s another collection of proteins inside the cell, and that is known as tau. Together, especially things go wrong, they can be very problematic. Again, with Alzehimer’s, problems start with the deposition of these amyloid proteins where the amyloid clusters and clumps together to form plaques. The plaques get bigger and bigger. They start to interfere with neighboring brain cells. There’s an inflammatory reaction, that causes the tau to be released inside the cells which forms long chains. The chains get tangled up. Eventually, these tangles kill the cells.

Why does this happen when people get older? There is a school of thought that I’m a believer in, that the normal function of amyloid in the brain is to help fight off brain infections. Bacteria, virus, fungi, things like that. We all make a little bit of amyloid every day, and we normally clear it away while we’re sleeping, which is one of many reasons why it’s important to get a good night’s rest. Well with Alzheimer’s patients, there either be too much amyloid being made, or not enough of it being cleared away. Tau tangles also can self-propagate. They can essentially move from one brain cell to another through the connections that brain cells have, and it can cause the tau to get tangled up in another brain region. Once this process starts, it can spread.

In terms of frontotemporal dementia, some of the proteins are the same. Unlike Alzheimer’s Disease which we think is a single pathology, in frontotemporal dementia, there’s like a family of maybe up to a dozen different pathologies, and roughly a dozen different abnormal proteins. The two that are most common are the tau and another protein that is called TDP-43. The 43 is how much it weighs in molecular weight, and the TDP stands for transactive DNA-binding protein. TDP-43 can affect people when they’re young and cause frontotemporal dementia for them in their 40s, 50s and 60s.

BrainWise: To what extent can these tau proteins help or contribute to the growth of someone’s brain?

Dr. Budson: The normal function of the tau is to help stabilize these very small tubes called microtubules inside neurons. Neurons have these long processes like long arms that reach out to touch other neurons, and that’s how the brain cells communicate with one another. In order to pass information and substances like proteins from one part of the neuron to another, neurons send them through these tiny microtubules.

BrainWise: Right now, how can people put themselves in a position to live longer and maybe stave off catastrophic memory loss?

Dr. Budson: We’ve really made tremendous strides over the last hundred years in understanding what causes memory loss, what causes dementia. We now understand the brain structures that are involved. We understand many of the abnormal proteins that are doing the damage. We are the furthest along on Alzheimer’s. There’s FDA-approved medications that can help to improve memory function among Alzheimer’s patients equivalent to turning the clock back on the memory loss. For people with FTDs, the main class of medications that can help these individuals if they have behavior problems are the Prozac family of medications, or selective serotonin re-uptake inhibitors. My personal two favorites in this class are Sertraline (Zoloft) and Escitalopram (Lexapro). Those I think work quite well in patients that are having behavioral problems, and there’s good evidence to show that these types of medications are helpful for them.

That’s just medicine. It’s important to engage in aerobic exercise, which releases growth factors from the brain that help us to grow new brain cells—no matter how old we are. Eating right is also important, and people should do their best to stay away from highly processed foods. Sleep is critical, and you want to try to get the right amount of sleep for you. That could be seven hours or nine hours, but I know it’s not five hours. Nobody’s right amount of sleep is five hours. People that try and sleep five hours or less not only have an increased risk of Alzheimer’s or other types of dementia, but they also have an increased risk of death. Other things that have been shown to be beneficial are staying socially active and engaging in novel, cognitively stimulating activities. There’s even a benefit from music.


BrainWise: What questions will you ask in your research next?

Dr. Budson: I am working on developing new strategies and memory aids that can help people to remember things better in day-to-day life without medications (or in addition to medications). Basically, I’m looking to extend the mild-memory phase of Alzheimer’s Disease. I’m also trying to understand the biological basis of thinking and memory and consciousness. I wrote a 30,000-word scientific article that was published in the December 2022 issue of Cognitive Behavioral Neurology. The article explains what I think is the relationship between memory and consciousness and about how if we understand this relationship, not only can we understand memory better, but we can also understand consciousness better. I’m excited about where it will lead.

BrainWise: Why did you choose to study this area of brain science in particular?

Dr. Budson: I’m particularly interested in memory and thinking. As early as high school, I really wanted to understand what are the biological bases of thinking, memory, and consciousness? I’ve maintained that interest throughout my career. Along the way a fascinating thing has happened. As soon as I started to care for patients, I found tremendous satisfaction at being able to help them with memory problems. I have been able to do that a little bit through medications, a little bit through strategies. The other thing that I found is that there’s a lot of neurodegenerative diseases, a lot of different types of dementias that we don’t have effective treatments for. With Alzheimer’s, we can do something, we can’t do everything. Frontotemporal dementia, we can do even less. I realized there’s a lot of good that can be done by just helping families understand what’s going on, helping individuals understand what’s going on with their thinking and memory or language or other types of things. I’ve always wanted to really understand what’s going on at a very deep level so that I can help individuals and their loved ones understand these things too.

If you’ve been diagnosed with FTD or you have a loved one who has been diagnosed, and want to understand more, please reach out to a NAN neuropsychologist or a neurologist for more information.

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Pieces of Her

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A son reflects on his family’s struggle with his mother’s dementia

She says she recognizes the hills and water and sky as we pull into the dirt parking lot at the head of the trail. Maybe the door to the unpredictable dark tower elevator of her mind has opened onto a familiar floor, and this will be a better day.

We carry our fly fishing rods down to the spring creek and I wade off the near bank, while she follows my dad a couple hundred yards upstream. Her encouraging platitudes as he casts his line drift watery relief around my bare calves. Finally, he’s able to do something fun, something he’s earned, without her demanding to be anywhere other than wherever they are.

After fewer caught fish than strikes I see her walking the trail back up to the truck. I yell and wave. She strains to shout that she’s just going to sit down, and she’ll see me soon. 

She sounds happy.

But I know what this may become, so I bring in my line, trudge out of the creek, and hustle up the trail after her. My dad is already ahead of me, trying to catch her before she gets to the truck. As I approach the open passenger door, she sputters in anger that she’s hot and doesn’t want to talk to me anymore. 

My dad hits the brakes on a bridge linking the dirt road to the two-lane highway, and asks her if she wants to see the bigger fish congregating in the shadows below. She whispers “I don’t want to” in between sobs, the toddler intonation reminding me of the year before when we were caught in a rainstorm in the Scottish countryside and all she could say was “I’m so cold.”

I watch her in the side mirror as the truck cuts home through the prairie. She fights and loses to waves of tears, her mouth turned downward in sadness, or anger, or something else entirely. Maybe she’s thinking about what’s happening to her now, or what happened to her as a kid in foster care.

I don’t really know. I never do. She doesn’t talk when she’s crying, but when they drop me off on their way to a doctor’s appointment, I open the passenger door, ask what’s wrong, and brush away the lone tear running down her cheek.

She shakes her head.

“Nothing to do with you.”

Which isn’t true, of course. Everything about this has something to do with me.

I shut her door, step back on the gravel driveway, and watch the truck disappear into the dust.

The truck, and another piece of her.

. . .

Many more pieces of her have fallen away since that trip to the creek. Pieces my father has tried in vain to catch, her fine grains of dust disappearing faster as he tightens his grip. Because if he doesn’t let go, she will still be with him.

As she has been for over 65 years, their number of nights spent apart fewer than the turning of autumn to winter. And so my father balls his fingers into a fist, minimizing his struggles with her violent mood swings and papering over her tendency to get lost, with assurances that she’s always been found. He doesn’t mention the police helicopter and missing persons report, or the skin torn from his forearm by her aggressive fingernails. 

Neurologist appointments have been scheduled and canceled over the years, a brain scan from 2016 never interpreted. Until last week, when we finally convinced my father to take my mom to a world-class neurologist. We thought that if we could help her, we could help him, because everyone in the family can see the toll that being her full-time caregiver is taking on him.

She was diagnosed, finally, with late-stage Alzheimer’s. And even then, my dad fought the neurologist, questioning the doctor’s confidence and requesting another current scan just to be sure.

My father and I manage much of life the same. But where he is seated in deep denial, I have tried to find deep acceptance by dealing with losing my mom the only way I know…turning inward to write both prose and lyric, and recording music seeded in the dirt of this journey. Not long ago I sang one of those songs to my mother, my voice breaking more for the sender than the woman sitting across from me, who I knew was losing each word as it was heard.

. . .

Where are you going
So far away
You’re further down the road
Every day

I don’t know what to do now
To bring you back to me
Where are you going
Amy

Sometimes I still see you
Like it was yesterday
Before autumn light on blonde hair
Faded to gray

Watching this ain’t easy
So I hold my memory
Sometimes I still see you
Amy

I hear a whisper on the night wind
I see a flicker in the dark
Along this road we travel
Searching for a spark

I’m going to start a fire tonight
With all the tender I can find
To light your slow walk home
Through this shadow in your mind

If you can see where you are going
The road will bring you back to me
The road will only be a circle
The road will only be a circle
The road is only a circle
Amy

. . .

And I suppose this is where I am now, years after that trip to the creek, days removed from a devastating diagnosis. 

Searching for a spark.

I guess I’m still holding on, too.

Alex Woodard is a writer based in Southern California. Learn more about him here.