Tag Archive for: Alzheimer's Disease

7 tips for navigating holidays with a loved one who has dementia

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The holidays are upon us, and whether your loved one is experiencing cognitive impairment due to Alzheimer’s disease, Parkinson’s disease, stroke, or any other cause, special planning and considering key changes to family traditions can help make the season more enjoyable for everyone. 

Amelia Anderson-Mooney, clinical neuropsychologist with private practice in Glasgow, Kentucky, and assistant professor of neurology and graduate medical education for the University of Kentucky College of Medicine, said a few small tweaks to annual rituals can go a long way toward making everyone more comfortable.

“Adjusting holiday plans appropriately often begins with a good understanding of what disease stage our loved one is experiencing now,” she said. “If symptoms are mild, small adjustments can make a world of difference.  If symptoms are moderate to severe, it’s likely that we will need to make more substantial changes. In mild stages, many elders with cognitive decline may be able to have a more active role in planning and preparing for family activities. In more advanced stages, their role will very likely be smaller but no less valuable.”

Here are seven tips for making the holiday season more comfortable for your loved one with dementia and everyone else.

Tip 1: Ask and learn

Sometimes we haven’t been fully aware of what our loved ones have been doing behind the scenes of our traditional holiday gatherings. When a loved one receives a diagnosis of dementia, it’s up to us to educate ourselves about the full extent of the responsibilities they have taken on over the years, and then have an open, direct discussion about what that loved one feels comfortable doing for this year’s holiday celebrations.

Anderson-Mooney said it’s important to make sure your loved one with dementia is involved in holiday preparation in a way that is meaningful to them. She said sometimes this can be accomplished by asking, simply, “What can we do to make the holidays easier for you?” Anderson-Mooney added that it’s critical to have this conversation with the understanding that elders with cognitive change may need additional time to gather their thoughts and respond.

“It is also important to remember some elders with cognitive change may not fully understand their limitations, which means a more substantial change in approach for us,” said Anderson-Mooney, who is a National Academy of Neuropsychology (NAN) board member and chair of NAN’s publications committee.

Tip 2: Delegate, delegate, delegate

If the person in your family with dementia is the person who has hosted holiday traditions, it might be necessary to rethink the entire celebration. Perhaps your loved one no longer feels able to prepare their home in a way that makes them feel ready. Perhaps they feel they can do it, but they need help. Anderson-Mooney said it’s always a good idea to offer to help make a list and gather volunteers to pitch in.

She added: If your loved one with dementia no longer feels comfortable handling the family meal solo, delegating tasks could be a golden opportunity to learn family recipes and traditions straight from the source so they can be passed down to future generations. 

Tip 3: Keep tabs on overload

Anderson-Mooney noted that it’s also important to consider how much holiday cheer loved ones can handle at one time.

People with cognitive change often talk about how overwhelming it is to be in large groups of people, even people they love, because they feel like they can’t follow the conversations well.  Because of this, they tend to withdraw, and that withdrawal can be hard for other family members to understand. If you have noticed your loved one having difficulty interacting in family gatherings during the year, your family may want to plan to have smaller gatherings more often. 

Her advice: Make sure you build the day around what your loved one’s body needs  Plan activities at a time of day when your loved one feels the sharpest and most energetic. Do your shopping outings before lunch. If your loved one feels and operates best in the morning hours, maybe a Thanksgiving breakfast is in order, with smaller visiting groups later in the day.

“The holidays are about being together,” Anderson-Mooney said. “That’s what matters most.”

Tip 4: Make travel easier

Cognitive decline often adds a layer of complexity if your family has traditionally traveled for the holidays. People with cognitive impairment often lean heavily on their daily routine to help them get by from day to day. Travel, by its nature, can disrupt that routine completely.

Anderson-Mooney said this means that travel might be out of the question for some people with cognitive impairment. She added that if a loved one has had trouble adjusting to relatively small changes in their daily routine at home, you can anticipate that they may not adjust well to the larger demands of traveling.

In extreme cases, or cases where a loved one is experiencing significant cognitive decline, it may be wisest to eliminate travel of any kind.

Tip 5: Build in time to rest

Sleep disruption can be very problematic for people with dementia. Anderson-Mooney said in practice, she often sees an increase in confusion and emotional upset from disrupted sleep. Again, if you have seen your loved one struggle to adjust to an earlier wake up time for a doctor’s appointment, or struggle to adjust to time changes or new time zones, for example, unusual holiday schedules or on quick trips can be doubly hard. 

Consider also that traveling itself—whether it’s a one-hour car trip or a six-hour plane flight—can be exhausting.

Most people are familiar with the fatigue we feel after reaching our destination when we travel, even though we’ve just been sitting in a car all day or waiting for a plane. This fatigue happens, at least in part, because our brains are very busy processing all the novel scenery, keeping us safe in traffic, making sure we make our flight connections, helping us remember where we put our carry on bags, and so on. Anderson-Mooney said this fatigue can multiply in a serious way in people with cognitive impairment.

“If travel is in the plans for your loved one with cognitive impairment, consider breaking up the trip into smaller legs or adding a day before and/or after to allow your loved one to recover energy-wise,” she said.

Tip 6: Line up support

If you’re planning to travel for the holidays by car, be very realistic about whether your loved one can handle any of the driving. If you’re flying, airlines help vulnerable elders just as they do for unaccompanied minors. Most of this assistance is available in part because of the federal Air Carrier Access Act and the Americans with Disabilities Act. Airlines are required to offer assistance for seniors such as help in boarding and making connecting flights, and many airlines go above and beyond the basic requirements to ensure that their elderly passengers are well cared for in their travels. (This, this, and this are great websites for more information on the subject.)

Anderson-Mooney suggested that family members may want to consider adding an extra layer of support for loved ones with dementia.

Specifically, she advised that someone in the family (or a hired caregiver) accompany your loved one as the person’s personal “travel coordinator.” This person becomes responsible for carrying your loved one’s medications, keeping track of their valuables, and tracking the itinerary. The person also can be responsible for making sure that your loved one takes their medications on time while traveling and while on the ground at the destination. (Setting alarm reminders on the coordinator’s phone is a helpful way to make sure your loved one never misses a dose.)

Anderson-Mooney said the coordinator should travel with a full, printed list of medications, dose amounts, and dosage times, as well as names and phone numbers of your loved one’s doctors. She added that it’s important to keep the list and the medication in a carry-on bag so it’s not lost and separated from your loved one.

“It’s so important to consciously and deliberately appoint someone to ensure these things are done,” Anderson-Mooney said. “With some medications, missing doses can be dangerous. Replacing medications in lost baggage can be done, but it’s better to avoid the hassle in the first place.”

Tip 7: Providing physical care

Finally, Anderson-Mooney said it’s important to be mindful to maintain our loved ones’ physical needs in the hustle and bustle of the holidays.

Make sure your loved one is eating good quality food on a regular schedule. Make sure they stay hydrated while out and about in town and during busy family gatherings. Be very careful and limited with alcohol consumption. Deliberately add in more time for rest and recovery in your schedule. Set medication alarms to make sure we remember to take medicines during our activities (taking water with us is often necessary for this).

Again, it can be very helpful to have a dedicated person or group of people to watch over these needs for your loved one. If this is too big of a job for one person, designate a different coordinator for each day of the holiday, and switch throughout the celebration. 

Closing thoughts

Of course, all these suggestions assume that your loved one is going to be an active, agreeable participant in adjusting to their own needs. Unfortunately, sometimes this is just not the case.

“Cognitive change is cruel and unforgiving, and it can completely change our loved ones’ personalities and ways of doing things,” Anderson-Mooney said. “Our loved ones may no longer be capable of understanding their own changes and adapting to their own needs. Our loved ones may no longer recognize us when we visit.  We might deal with more agitation and anger, more upset, lashing out behavior. In these cases, our traditional plans just don’t make sense anymore.”

In these worse-case scenarios, Anderson-Mooney said we must adapt to a much heavier degree.

Specifically, if visits usually leave your loved one agitated and upset, it may be best to delay the holiday all together.

If visits leave your loved one confused, it may still be worth making the effort to celebrate together. Anderson-Mooney added that even if your loved one no longer recognizes you, they are very likely to recognize and understand that you are someone who loves and cares about them. They will appreciate your gesture of time and company, small gifts and comforts, favorite foods, and chatting about family photos. Spend time listening to their favorite music. Talk about their favorite memories from the past. Take the time to write down the family stories they tell before they fade away.

“This time can be a gift, even while you mourn the changes your family is experiencing,” Anderson-Mooney said.  “Give the best love and honor that you can, and know that it matters, whether or not your loved one can appreciate it.”

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

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.

Physical activity a key to brain health

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One of the missions of the National Academy of Neuropsychology (NAN) is to make facts about brain health available to as many people as possible.  That’s precisely why NAN recently released a quick tips video with information related to the connection between physical activity and brain health.

The video, part of NAN’s new Brain Health Hub, features NAN President, Dr. John Randolph, who also is a clinical assistant professor of psychiatry at Dartmouth University.

While we’ve known for many years that being physically active is important for general health, heart health, and our mood, we now know that being active through exercise and daily movement can do many things for the brain too.

Being physically active on a regular basis is linked to a stronger ability to focus, learn, remember, and solve problems in daily life.  Benefits from exercise workouts, in particular, can happen after individual sessions, and can also happen if we exercise and stay active day to day, and week to week.

What types of physical activity count? Going on walks, hiking, dancing, cycling, doing yardwork, swimming, and many others are all good for the brain—anything that gets your heart beating a little faster than usual for at least 20-30 minutes at a time seems to be the sweet spot for improving brain health.

In this process, we can even form new neurons, or brain cells, in the memory center of the brain. 

One other thing: Exercising on a regular basis is associated with a significantly reduced risk of developing Alzheimer’s disease.  Even if you’re not very physically active much right now, by starting to move and exercise more often, you’ll be helping your brain stay healthy, and you may avoid problems many years from now.  

Leaning into a new exercise regimen isn’t easy. If you’re having trouble building a new exercise habit, consider taking small steps first, such as going on short walks once or twice per day.  Exercising with a friend might help improve your motivation to work out, and there’s evidence that exercising with someone else might be even better for brain health than exercising by yourself.

For more information about the connection between physical activity and brain health, or for information about other aspects of brain health, please visit NAN’s Brain Health Hub, a growing library of resources on the NAN website.

Hemsworth raises awareness about genetic testing and dementia

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It turns out Thor might be mortal after all.

More than anything else, that was the takeaway from a recent episode of “Limitless with Chris Hemsworth,” the NatGeo documentary series on longevity.

In the show, the Australian actor who plays Thor took a genetic test that revealed he has two copies of the gene APOE ε4, which is linked to an increased risk of Alzheimer’s disease. A recent Men’s Health magazine article thrust the issue like a hammer (see what we did there?) into the national zeitgeist.

This article, published October 3, noted that Dr. Peter Attia, who specializes in longevity and is the consulting doctor on “Limitless,” explained to Hemsworth that while this gene increases the risk of Alzheimer’s—making it somewhere between three and 10 times higher than everyone else’s—it’s doesn’t mean Alzheimer’s is a sure bet.

In other words, according to Dr. Attia, a patient can have the high-risk gene without ever developing the disease. Conversely, the same patient may not have the gene and can still develop Alzheimer’s.

Ten years ago, researchers knew of only 10 genes linked with Alzheimer’s. Today, scientists have identified more than 70 genetic regions associated with Alzheimer’s. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer’s.

APOE ε4 increases risk for Alzheimer’s and is associated with an earlier age of disease onset in certain populations. A 2015 JAMA report indicates that with an allele frequency of 14 percent, APOE-ε4 is present in approximately 25 percent of the US population and associated with increased risk of Alzheimer’s Disease.

What’s more, a separate report from 2021 indicates that roughly 2 to 3 percent of those who carry APOE-ε4 actually carry two copies like Hemsworth does.

(We all always knew that Thor was an extraordinary specimen; for more on the research, click here.)

Risks associated with having APOE ε4 are manageable. On the “Limitless” show, Dr. Attia said he believes that with aggressive lifestyle adjustments one can reduce risk.

Specifically, Dr. Attia told the 40-year-old Hemsworth he considers Thor’s test result a blessing. “This will motivate you to take steps today that most people [in their 40s] would never think about until they’re in their 50s or 60s,” he told the star.

Hemsworth, in turn, responded with signature panache.

“It was a good kick in the arse and a reminder to do whatever is in my power to give myself the best fighting chance,” said Hemsworth. “Whatever work I’m doing for my brain health benefits the rest of my body—we turned it into a positive.”

In the article, Hemsworth added that he hopes sharing his news will inspire other people in similar situations to take better care of themselves.

Specifically, he told Men’s Health Executive Editor Ben Court that people in similar situations should “either go and get checked or to understand more about brain health and see what they have within their power to change.”

Hemsworth also cited impacts of focusing on certain areas of brain health, including diet and sleep.

To be clear, in most cases Alzheimer’s does not have a single genetic cause. Instead, it can be influenced by multiple genes in combination with lifestyle and environmental factors. According to the National Institutes of Health, a person may carry more than one gene or group of genes that can either increase or reduce the risk of Alzheimer’s.

Importantly, people who develop Alzheimer’s do not always have a history of the disease in their families. Still, those who have a parent or sibling diagnosed with the disease have a higher risk of developing Alzheimer’s than those without that association.

(Additional studies by NAN’s own Archives of Clinical Neuropsychology journal have established that APOE ε4 is connected with an increased likelihood of neurocognitive impairment following sports-related concussion, and that the presence of APOE ε4 can be a predictor of heterogeneity in cognitive function.)

It’s also worth noting that genetic tests are not routinely used in clinical settings to diagnose or predict the risk of developing Alzheimer’s or a related dementia. In some cases, if a person has symptoms at an early age with a strong family history of Alzheimer’s, a neurologist or other medical specialist may order a genetic test for rare single-gene variants known to cause the disease.

As mentioned earlier, although APOE testing is also available, the results cannot fully predict who will or won’t develop Alzheimer’s. Rather, this type of testing is used primarily in research settings to identify study participants who may have an increased risk of developing Alzheimer’s. This approach helps scientists look for early brain changes and compare the effectiveness of possible treatments for people with different APOE profiles.

In Hemsworth’s case, it also makes for great TV, and an impetus for change.

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

Mourning of the inanimate

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It wasn’t the first time I had migrated from one parent’s house to the other’s. Eleven miles door-to-door and a world apart. “Something was wrong” with Mom, but a diagnosis was at arm’s length. As imperative as it was to address the jarring interruption to what I had previously understood her to be, getting an answer was paralleling the first page of what was expected to be a poignant new life chapter.

I hesitated to turn the page.

Having stretched the task over several weekends, I moved my belongings into Mom’s house. I was a broke thirty-something who had spent the totality of my savings a couple years prior on a six-and-a-half-month solo road trip around the United States. It was early September 2019, and I couldn’t afford to continue paying my dad the few hundred dollars a month he was charging me for rent. The bucket list travel had been a lived-out dream I’d repeat a thousand times over if I could, but after the trip I was back to substantiating paycheck to paycheck. With pride tucked between my legs, I went from low rent to no rent, accepting a humbling perk of familial cohabitation as an adult.

I recall placing my camera on a rocking chair in the front room of her house, a temporary placement among the boxes of knickknacks and clothes. It sat tucked inside an innocuous black bag, unbecoming of its gravity. My out-of-date smart phone had sufficed for documenting worldwide travels for years, but I had recently upgraded to point-and-shoot. To this day I am proud of all I had captured on the phone, but there’s an ego feeding self-assurance to finally owning “real” photography equipment.

Months after my previous birthday Dad casually offered to give me money toward a camera. (Originally, he opted to fund a hitch for my car, but after I did not take him up on the original offer, he concluded there was little interest in that specific generosity.) But I sure did perk up when he came across a springtime Target ad for a Canon Rebel bundle, a suitable starter kit for an amateur photographer looking to upgrade her equipment. Forty-five minutes after the proposal I was standing in the electronics department of the store waiting for the employee to unlock the glass display case. The heart palpitations confirmed that this was the gift for which I had been longing. Dad graciously understood the impact of the pivot when I returned home with the box clutched tightly in my hands and a giddy, beaming smile as matching accessory.

Mom always fed my hunger for creativity. With an appropriately supportive “Oh honey, that’s amazing” (or something of the like), she never failed to recognize each project regardless of its juvenile-handed craftmanship. My interest would wax and wane with varying mediums, but a few became woven into my being. I requested trips to the local craft or fabric store to garner beads for jewelry making, stamps and thick, velvety paper for homemade cards. These treasures would join the hoarded bins of paints and markers, journals, and dress-up clothes. Menus were made for special occasion meals that I crafted for hours; a home-room newspaper was fashioned with peers. To my dismay she riffled through bedroom drawers to read emotive poems about boys or depression, and embarrassingly, angsty notes directed toward her. It wasn’t lost to me that any good mother ought to express encouragement in their child’s interests, an obligation of love. As I got older, I understood this silent agreement between us that I would create and she would “Oooo” and “Ahhh,”but my ego luxuriated in it regardless.

In adulthood I narrowed my artistic efforts to writing, drawing, cooking, and later, photography. Honing them was continuous and boundless, a new-to-me definition of infinity. There was always more to make, lenses of perspectives to try on, skills to learn. Enter Alzheimer’s. Even as Mom faded, she was there for all of it. The more she leaned out of reality, the more I realized how precious her gift of support was. It’s intangible in the traditional sense, but it’s there in every production of my mind’s eye.

As of that move-in day, most of the photographs remained on the camera’s memory card. There was no urgency to upload and edit them at will. Their existence remained in the suspension of a plastic chip the size of a thumb, tucked in a cavity of the camera, hidden from the bright light of the living room by the protective barrier of a travel bag. A non-descript item amongst many, waiting to be unpacked into new shelves and drawers and wicker baskets for the guise of organization.

These were the tokens of the camera that I collected with gumption: Inky Joshua trees backlit with sorbet desert skies. Swirly rock striations of rust and cream, bookmarks of time. Brick walls swathed with city smog, fingertips, and speckled blood of unnamed revolutionaries assassinated by defunct reasonings. A sunrise more volcanic than its conical counterpart, igniting a landscape monument in the crook of its arch only in the brevity of time when light first reached it each morning. Tufa formations and earthy tears pooled into a lake more alien than Mars.

It wasn’t until weeks later, when I went to grab the camera to document an afternoon hike, that I realized it was missing. The longer it was out of sight, the more panic overtook me. Subsequently there were several occasions of feverishly looking in every space of the house to try and locate it. No, it wasn’t in any of the closets. Nor was it in the last of the moving boxes or under any furniture. The garage hadn’t gobbled it up.

Where the hell was it?

As revelations often are, a thought was born with certitude out of the nothingness of an ordinary day.

Again, I recalled bringing it into the house and gingerly setting it on the rocking chair to prevent it from getting jostled or knocked over. But this time I also remembered how Mom wanted to help with the move. In those earlier years she still maintained a compulsion to clean and organize, so she volunteered to pick up boxes and other nondescript packing materials as I unpacked. The human-sized black trash bag she held in my memory screamed at me. This was the first time I considered that Mom threw the camera—bag and all—away.

Was this truth? Or was I succumbing to the human urge to place blame on others for my own misplaced possessions? I didn’t care. The likelihood of the explanation seemed too obvious. I let the weepy, exasperated self-pity and tear-soaked hyperventilation take over. A still frame of the camera sitting mournfully in the garbage bin outside overtook my sanity. Of all the things she could have thrown away accidentally, why did it have to be that?

I can’t say for certain if I confronted her, but I have a feeling that I did. Not the shiniest reactionary decision to burden or shame my most consistent supporter when it was the disease, not her, that disposed of the camera.

Four years later, when I found mom a placement in a memory care facility and began moving out, the overwhelming suspicion was all but confirmed. Aside from the decluttering I had done during the pandemic and multiple wildfire evacuations, there were months upon months of preparation for the inevitable next step. The house needed to be renovated and staged to be sold. The profits were the only way to pay for Mom’s expenses as a soon-to-be resident of a place where others would care for her. I was both being set free from caregiving and saying goodbye to a version of us that we’d never meet again.

In my last hours at the house, I breathed in the bareness of each room. There was nowhere for a camera to hide. No corner or nook unexamined. Every possible resting place had been eliminated. It stung less than before, but I mourned it along with the swelling of so many goodbyes. Admittedly, that specific anguish had dulled when a stranger had gifted me the exact same camera bundle sometime in the last months before moving.

I had come across an online posting in a neighborhood group. The owner of the camera wanted to give it to someone who would use it with much more gumption and appreciation than she had. Close to a hundred people left comments of varying degrees, asking to procure the unusually high-value offering. My own comment thanked the woman for her generous act of kindness and briefly explained that my Alzheimer’s ridden mother had accidentally thrown mine away. It was the truth, but still felt slightly sticky to expose the transgression. I was sure that the camera would find its way into someone else’s hands, anyway. I had never seen so many responses to a post before.

Instead, this wayward camera became mine.

There is still disbelief when I see the device and its pack nonchalantly sitting in the room of my new home. It’s like the space in a book between the end of the last chapter and the beginning of the next. Definitive. Small, yet vast with meaning despite being nothingness sandwiched between the profound.

Sometimes I speak a quiet offering of gratitude to the woman, but also for my mother. It felt like everything had come full circle. Surely, somehow, Mom had a hand in that. 

For additional information about processing grief and loss as Alzheimer’s disease progresses, visit this Alzheimer’s Association page on the subject. Another good resource for families: The 36-Hour Day.

This essay has been factchecked by members of NAN’s Publications Committee. For more about that process, click here.

Lauren Ahlgren is a writer and swim instructor in Bend, Oregon.

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.

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.