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What not to miss at the 43rd annual NAN Conference

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The National Academy of Neuropsychology (NAN) is set to celebrate its 43rd annual conference this week in Philadelphia, and the event is shaping up to be interesting, informative, and integral to understanding where brain science is headed.

NAN has lined up dozens of speakers to present an eclectic program. These neuropsychologists and other researchers will opine on everything from concussions to the Mediterranean Diet.

NAN Executive Director Dr. Bill Perry said he is looking forward to the breadth and depth of expertise.

“Neuropsychologists are always the busiest people I know,” he said. “This is the one time all year when we stop what we’re doing, get together and listen to each other to get a sense of what we’re all doing and where the field is heading next. Year after year, NAN is excited to be able to facilitate this confluence of minds.”

There are 52 sessions over three-and-a-half days of programming at the Philadelphia Marriott Downtown. Here are just some of the sessions about which attendees undoubtedly will be talking:

Wednesday, October 25

First, in a welcome plenary titled, “Three Lessons About the Brain (or Stuff I’ve Learned From Studying Emotion),” Dr. Lisa Feldman Barrett will describe three insights about brain architecture and the corresponding computational affordances from the science of emotion. The welcome session begins promptly at 1:15 p.m.

Later in the afternoon, Dr. Michelle C. Carlson will deliver a talk titled, “Promoting Cognitive and Brain Health through Social Engagement and Neighborhood Factors.” This talk will summarize work increasingly focused on multi-domain dementia prevention interventions and describe work that incorporates social and productive engagement. Dr. Carlson also will describe the rationale for research examining the intersection of individuals and their environment or neighborhood, when examining cognition, function, and brain health.

Toward the end of the day, Dr. Paul Thomas Maruff will discuss the intersection of cognitive dysfunction and preclinical Alzheimer’s Disease. Dr. Maruff will highlight how attempting to understand this disease stage with both conventional and computerized cognitive tests provide new challenges and lessons for the field of neuropsychology. The talk is titled, “The Nature and Magnitude of Cognitive Dysfunction in Preclinical Alzheimer’s Disease: What The Disease Tells Us About Neuropsychology and What Neuropsychology Tells Us About The Disease.”

Thursday, October 26

Day 2 of the conference kicks off with a symposium titled, “The SuperAging Research Initiative: Identifying Protective Factors to Promote Healthspan.” Because the initiative spans three sites, this particular talk will comprise three speakers. Dr. Emily J. Rogalski will provide an overview of the initiative including rationale, known features, current progress, and new directions. Dr. Amanda Cook Maher will provide insights on outreach, recruitment, and engagement approaches. Dr. Angela C. Roberts will describe the innovative remote data collection protocol and initial observations from the wearable technology used in the study, which is designed to quantify measurements of daily life including sleep, physical activity, autonomic responsivity, and social engagement.

Next, Dr. Gayathri J. Dowling will deliver a talk titled, “The Adolescent Brain Cognitive Development (ABCD): Opportunities for Scientific Discovery.” In this session, Dr. Dowling will describe the comprehensive nature of this longitudinal study (including the many different types of data being collected), and discuss emerging findings from the ABCD study and describe its potential value for understanding risk and resilience factors that influence adolescent development.

NAN Executive Director Dr. Bill Perry will deliver a talk on Thursday, as well—a session titled, “The Role of Neuropsychology in Evaluating Physician and Pilot Fitness for Duty: Ethical, Legal, and Clinical Considerations.” In this presentation, Dr. Perry will summarize the various types of physician assessments and the legal and ethical issues associated with each type. His co-presenter, Dr. Robert Elliott, president of Aerospace Health Institute—LAX, will describe the aviation evaluation process and the qualifications required to conduct mental health and neurocognitive evaluations required by the Federal Aviation Administration.

Finally, in a talk titled ” Positive Emotions in the Regulation of Stress: A Neuroaffective Model with Applications for Resilience,” Dr. Christian Waugh will introduce a neuroaffective model of how people use positive emotions to regulate their stress. This model contributes to the stress/emotion regulation and neuroscience literatures by outlining multiple psychological mechanisms through which positive appraisal helps promote resilient responses.

Friday, October 27

The third day of the conference is by far the busiest, with several talks happening simultaneously during the morning session.

One from Dr. Robert Motl, titled, “Effects of Exercise on Cognition and Other Variables in Multiple Sclerosis,” will review the evidence regarding the effects of exercise training on cognition, mobility, and quality of life in people with multiple sclerosis (MS); another. In another talk titled, “Neuropsychological Outcomes in Pediatric Cancer Survivors: Clinical Management and Emerging Research,” Dr. Peter Stavinoha and Dr. Marsha Gragert will provide an overview of the current understanding of factors associated with cognitive and educational outcomes for pediatric cancer survivors.

After lunch, Dr. Gabriel de Erausquin will deliver findings from recent research into cognitive impairment profiles of older adults after SARS-CoV-2 infection as part of a talk titled, “Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2.” (BrainWise published a Q&A with Dr. de Erausquin earlier this year.)

To end the day, Dr. Maria T. Schultheis will drive (see what we did there?) a discussion about how technology can help patients drive after neurological compromise. Titled “Technology, Cognition and Driving: What Have We Learned and Where Are We Going?” the talk will summarize current research in this area and highlight emerging technologies that can further contribute to understanding of brain-behavior functioning.

Saturday, October 28

The final day of the conference is a short one, and several early-morning talks are compelling.

A workshop titled, “Social Justice and Brain Health Science Futures: Testing, Training and Research Applications,” will offer offers professional development though a lens of social justice that builds upon available empirical evidence and historic records to establish foundational understanding of the current scientific landscape of brain health disparities. Led by Dr. Desiree A. Byrd, the talk also will inform practice enhancements for clinical and research evaluations that yield equitable assessment experiences for populations most susceptible to brain health disparities.

In another morning session titled “Technology Strategies that Support Cognition to Improve Health and Everyday Function,” Dr. Maureen Schmitter Edgecombe and Dr. Tania Giovannetti will discuss and share findings from clinical studies that use personal technologies, including smartphones, smart watches, tablets, and laptops to scale and deliver cognitive interventions that support cognitive abilities and improve everyday function.

The conference will conclude with a plenary session delivered by Dr. Antonio Damasio during which he will explore the biology and psychology of human consciousness. The closing plenary will begin promptly at 9:30 a.m.

BrainWise Managing Editor Matt Villano will be on site publishing daily reports from the conference. Also be sure to follow the official BrainWise Instagram account for more.

Finally, if you’re a neuropsychologist and you’re attending the conference this week, be sure to check out this article, from The New York Times, about the best 25 restaurants in Philadelphia right now.

Three decades of fighting for brain health

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U.S. Representative Bill Pascrell (D-N.J.) has established himself as a champion of brain health. The 86-year-old Army veteran has represented the Ninth Congressional District since 2013 and served in the House since 1997. During this time, he has leveraged his leadership in several ways to protect the brains of Americans. First, in October 2008, after the death of a young boy in his district who returned to playing football without having fully recovered from a concussion sustained earlier in the season, Pascrell introduced the Concussion Treatment and Care Tools Act (ConTACT), which has been endorsed by the National Football League, the National Football League Players Association, and the Brain Injury Association of America. ConTACT brings together a conference of experts to produce a guidelines for the treatment and care of concussions for middle- and high-school students. It also provides funding for schools’ adoption of baseline and post-injury neuropsychological testing technologies. Later in his tenure, in 2013, Rep. Pascrell introduced the Traumatic Brain Injury Reauthorization Act of 2013 (H.R. 1098; 113th Congress), a bill that reauthorized appropriations for Centers for Disease Control and Prevention (CDC) projects to reduce the incidence of traumatic brain injury and projects related to track and monitor traumatic brain injuries. The National Academy of Neuropsychology is honored to celebrate the leadership of Rep. Pascrell at its forthcoming annual conference in Philadelphia. In advance of that event, BrainWise Managing Editor Matt Villano spoke with Rep. Pascrell about his work and his commitment to brain health. What follows is a transcript of that exchange.

BrainWise: Why did you get into politics in the first place?

Rep. Bill Pascrell: A native son of New Jersey, I have built a life of public service around the principles I learned while growing up on the south side of Paterson. My parents and Italian-immigrant grandparents instilled the value of being a bridge builder: one who seeks to bring together the diverse peoples and neighborhoods in our communities to forge a better society. I was proud to serve in the New Jersey State Assembly in the 1980s and became mayor of my hometown Paterson in 1990. I entered Congress in 1997.

BrainWise: Since you became an elected official, you have been a champion of more than 6 million Americans who live with debilitating brain injuries. What sparked your interest in fighting for these issues, and how did you come to recognize this important group of citizens?

Rep. Pascrell: It bothered me that these Americans were too often being forgotten. Traumatic brain injury is a devastating debilitation that impacts not just its victims, but also their families and friends. I felt these Americans needed a champion in Washington and I have tried to be that champion. I founded the Congressional Brain Injury Task Force in 2001 to increase awareness of brain injury in the United States. [The organization also] supports research initiatives for rehabilitation and potential cures, and strives to address the effects such injuries have on families, children, education, and the workforce.

BrainWise: What inspired you to create this task force? What is the work of this group?

Rep. Pascrell: In 1998, I met a Clifton, New Jersey, constituent named Dennis Benigno, whose 15-year-old son had suffered a severe traumatic brain injury from an automobile accident that left him disabled. The Benigno family’s passion and dedication in finding a cure for their son and millions of others was my inspiration to act in Congress. Through the Task Force, I work on a bipartisan basis to raise public awareness of brain injuries among Americans of all stripes. We try to bring both federal support and public support to bear here. Public awareness is everything.

BrainWise: You co-chair the task force with Rep. Don Bacon, a Republican from Nebraska. At this time of such division in Congress it appears that you have been able to work across the aisle for this important cause. How?

Rep. Pascrell: On commonsense issues, compromise is not just possible but essential. When I speak with my Democratic and Republican colleagues on the need to raise awareness for brain injuries, they understand, and they are eager to get involved. Both parties working together has helped secure hundreds of millions of dollars to advance awareness and support those with traumatic brain injuries. We have passed legislation that recognizes the life-altering impact and supports researching into brain injuries that has affected millions of Americans.

BrainWise:  You have also been instrumental in bringing awareness to those who have experienced blast injuries; this resulted in The National Defense Authorization Act for Fiscal Year 2020. Why was that act so important, and why is it so important to help those who have suffered from these traumatic brain injuries?

Rep. Pascrell: This federal support has been critical to aid Traumatic Brain Injury victims. It is one thing to talk the talk and another to walk the walk. Politicians can speak a big game, but enacting actual federal aid is the key, and we have done that with these pieces of legislation we have gotten signed into law. That bill included language that I pushed for on blast exposure. Specifically, my language ensures blast exposure history will be recorded in medical records of servicemembers, requiring the enclosure of critical details including the date and duration of the incident. The National Academy of Medicine has concluded that servicemembers with blast exposure history are at increased risk of long-term health issues, including depression, Alzheimer’s-like symptoms, seizures, and problems with social functioning. Optimizing the readiness of servicemembers and recording blast exposure data is essential so that soldiers receive proper care for any service-connected medical issues that may arise later.

BrainWise: Finally, the issue of Chronic Traumatic Encephalopathy (CTE) is one we see grabbing a lot of headlines these days. Research into what causes this is ongoing, and early studies indicate CTE is not as connected to repeated head injuries as the mainstream media has portrayed. To what extent do you think our government should get involved in regulating activities that could potentially lead to CTE?

Rep. Pascrell: I think it starts with focusing a bright light on these problems. Congress can do that very well with hearings, public events, and public statements.  I have demanded answers from leading sporting organizations about how they are protecting athletes and students. Our kids and future generations are learning more and more about these harms, and we cannot treat them lightly.

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.