Tag Archive for: treatment

New Brain Beat podcast features Dr. Tresa Roebuck Spencer

The Brain Beat podcast, which is published by the National Academy of Neuropsychology (NAN) Foundation, has shared its latest episode: A gut-wrenching interview with neuropsychologist and former NAN President Dr. Tresa Roebuck Spencer.

As BrainWise wrote in a Q&A feature article earlier this year, Dr. Roebuck Spencer has a glioblastoma multiforme (GBM), a fast-growing and aggressive cancerous brain tumor.

Since her diagnosis in October 2020, Dr. Roebuck Spencer has managed the roller coaster of treatment (including four brain surgeries, three clinical trials, two rounds of radiation and chemotherapy), as well as the ups and downs that have come with transitioning from expert to patient.

Earlier this fall, she did some public service announcements for the National Brain Tumor Society (NBTS).

(As an aside, the NBTS provided statistics and data that informed this blog post, which ran as a companion piece to the BrainWise Q&A.)

In the podcast, Episode 15, Dr. Roebuck Spencer talks more about her new life as a patient, and about some of the challenges she is facing today. She also looks back on her journey—sometimes even with humor.

Dr. Roebuck Spencer has had an incredibly accomplished career in neuropsychology. The Houston-based doctor is a board-certified clinical neuropsychologist who has worked in Texas, Louisiana, Florida, and Washington, D.C. She has published more than 70 peer-reviewed publications and book chapters in the areas of traumatic brain injury, rehabilitation, and computerized neuropsychological testing.

All episodes of Brain Beat can be accessed here.

What happens when you treat depression with ketamine

It was a Wednesday afternoon. March 27, 2019. The out-of-office notification popped up on the team calendar at my corporate job. I told everyone I had a “doctor’s appointment” – technically accurate, yet spiritually a lie. I wasn’t going to the doctor’s; I was going to space.

Okay, not actual space–a ketamine clinic just a block or so away from the University of Texas at Austin. I answered a few clipboards full of questions. They sat me in a chair, read my blood pressure, and asked me “What is your intention for today’s infusion?” I do not recall my answer.

Then the infusionist hooked me up to an EKG and poked a vein. The machine beeped and the bag began to drip. The next hour was the weirdest of my entire life–I was about to go into a K-hole to treat a depression I’d been battling for years.

Why I chose ketamine

I received my first official diagnosis of major depressive disorder in the spring of 2001. I was a freshman at Syracuse University, struggling with being a working-class kid from the Rust Belt at a prestigious private school that was a popular magnet for the types of kids we’d call “nepo-babies” in today’s parlance. I was not taking great care of myself. I exercised but forgot to eat. I made friends but not as quickly as I lost them. Occasionally, I even went to class. I got good grades but felt like a misfit.

For treatment, I tried Zoloft. I saw a social worker for counseling. I can’t say either worked. This began a years-long journey on therapists’ couches and doctors’ pills, trying to understand why I felt so sad, anxious, and broken – and, hopefully, feel better. My mental health waxed and waned, but in late 2018 I was low enough (and well-off enough) to try new alternatives.

When my counselor first suggested ketamine infusion therapy after my latest 90-day course of Lexapro yielded unremarkable results, I recoiled. I was never a fan of “drugs.” Too scary. Too much can go wrong. I saw kids put powdered ketamine up their noses in college, sink back in their chairs, and fall out of touch with reality. I thought to myself, “That looks like no fun at all and I’m never going to do that.”

Never say never, I guess. My counselor assured me I would be safe. “I can refer you. I’m good friends with the woman who runs the clinic and her husband’s the doctor there. They’ll take good care of you.” Eventually, I acquiesced. Weeks later, there I was in the chair: determined and pot-committed. I paid $500 to be there (and $3,000 for the initial course of treatment) and put my faith in this Y2K-era club drug. I had some good research on my side.

How ketamine works

Developed in 1962 as a dissociative anesthetic, chemists created the novel compound to be a safer and less hallucinogenic alternative to phencyclidine (PCP). At anesthetic doses, ketamine provides pain relief, sedation, and amnesia. Breathing function is preserved, your blood pressure rises, and your pulse ticks upward. It’s short-acting and quickly metabolized, providing relief within seconds and acute effects that last for an hour or less. It’s antidepressant potential was first noted in 1975.

Unlike conventional antidepressants, which target monoamines, ketamine acts upon the glutamate system of the brain as an N-methyl-d-aspartate (NMDA) receptor antagonist, mediating activity of GABA and glutamate neurotransmitters. Glutamate plays an important role in modulating responsive synaptic changes related to experiences associated with learning and memory.

If how ketamine works is unusual, how fast ketamine works is genuinely unprecedented. Recipients notice an improvement in mood within hours–improvements that can last over a week on their own and, when coupled with integrative therapies and proper care pre- and post-infusion, can last for months if not years.

Researchers at the University of British Columbia conclude, “[Ketamine’s] effects may ‘reset the system’ by counteracting the synaptic deficits, neuronal atrophy, and loss of connectivity in depression.” If you think of the brain as a computer–ketamine appears to perform a soft reboot, a quick start, a system restore, a hard-drive cleanup, and defragmentation all in one.

Ketamine’s ace in the hole is the way it appears to actually “rewire the brain” by increasing neuroplasticity. The brain can heal itself more easily by allowing new neural pathways to develop. Theodora Blanchfield, AMFT, a Los Angeles-based ketamine therapist posits that “the new neural pathways—think of them as new roads in your brain—allow you to create more positive thoughts and, therefore, behaviors. This is compared to traditional antidepressants, which only work as long as they are in your system.”

We can even observe this rewiring visually. In 2022, University of Pennsylvania researchers reported that ketamine switches off specific neurons involved in normal awake brain function and switches on an entirely different and previously inactive set of cells – believed to be a network of cells that enable “dreams, hypnosis, or some type of unconscious state”.

In an interview with Harvard Gazette, anesthesia researcher Fangyun Tian, Ph.D., summarized her own research by drilling down even further, reporting “high-frequency gamma oscillations in the prefrontal cortex and the hippocampus known to be involved in ketamine’s antidepressant effects from other studies.” Additionally, the researchers “found a three-hertz oscillation in the posteromedial cortex that another study showed might be related to ketamine’s dissociative effects.”

These gamma oscillations appear to promote the profound changes in cognition and perception that permeate the psychedelic experience–and also appear to aid in shaking the brain out of the “default mode network,” allowing people to more easily experience mental health breakthroughs and behavioral shifts.

Research into the potential applications yields buzzy headlines and buzzier results, suggesting ketamine-powered neuroplasticity improvements can aid in everything from OCD to PTSD to smoking cessation to alcohol use disorder to learning to tolerate tropical house music.

If this all sounds a bit bullish, it doesn’t come without risks or unknowns. While generally (and often exceptionally) safe, especially in short-term clinical settings, adverse side-effects among long-term clinical ketamine recipients include impairments in memory, executive functioning, self-awareness, and increases in emotional blunting and reward processing. Additionally, a 2022 review published in Frontiers in Neuroanatomy proposes that long-term recreational ketamine use was “associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity.”

How a therapeutic K-Hole actually feels

My ketamine infusion treatment course consisted of six doses over three weeks. I received progressively increasing amounts, starting at 50mg and ending at 200mg. While no two infusions were alike, they were similar enough to be able to speak about them in broad strokes. Each infusion took about an hour. They started slowly, gradually warmed up, peaked, then waxed and waned in their cognitive distortions until the last drop. The emotional whiplash was sudden, frequent, random, and severe. I laughed, cried, and screamed – sometimes all at once. All the while, I felt a warm glow, a genuine sense of awe-struck wonder, and a slight tinge of dread that this could all go very wrong at any given moment.

Immediately after each dose, I journaled my thoughts in an attempt to remember as much of what I had just experienced as I could. I described the infusions as a “solo space flight,” the Antoine de Saint-Exupéry novella “La Petit Prince,” a journey into “the operating system” of reality to modify the UI and UX, “a wafer-thin atmosphere buffering a sort of meta-reality, enveloped by a dark abyss of nothingness, monitored by scientists in lab coats,” the “minus world” video game glitch in the original Super Mario Bros., and “the flume ride in the Mexico installation at Disney’s EPCOT theme park.” By the final infusion, I started coining terms like “soul meridian” and comparing myself to Simba from The Lion King and the Manchurian Candidate.

Other common ketamine experiences for me included: speaking in perfect French with my dead Papa as a young man at a Parisian cafe, faceless people performing heavy industrial work, feeling as though I’m hanging from the ceiling, feeling watched by MK Ultra-era government medical observers, staring in the direction of a precipice that never quite arrives, and a procession of formless deep blues and greens that wash into each other.

One frequent recurring experience was what I call the “coffin moment.” Approximately two-thirds of the way through most of the infusions, the chair in which I was sitting in folded into a coffin that rose from below the floor and onto a stage where people passed and pay respects. Then I levitated and floated toward a bright light on a well-lit path (think: Rainbow Road from Super Mario Kart). My life fast-forwarded like the climax of a montage that ended in silence and white stillness. I walked to a white door. That was when I heard a voice whisper “not yet,” and I dropped back into my body. I didn’t always make it all the way through that progression–sometimes I ended at the rising coffin–but the moment always played out the same: I was dead and I shouldn’t have been. Then the ketamine subsided.

For as insane as “pretend death” sounds, it’s not uncommon in a psychedelic context. In fact, ketamine is so adept at simulating near-death experiences that there’s peer-reviewed literature detailing the phenomenon. People taking clinical doses of ketamine report experiencing these sensations with uncanny levels of accuracy and consistency.

Not all of my ketamine infusions were pleasant; on two occasions out of the roughly 40 (including boosters) I’ve received, my hallucinations were so painful and intense that I had to cut the infusion short. On a handful of other occasions, my blood pressure spiked to levels that caused clinicians to draw the same dosage out over 75 or even 90 minutes instead of 60.

Still, at doses that cause full dissociation–approaching anesthesia–I progressed through states of curiosity, childlike immersion, omniscient appraisal of life and reality, existential dread, death, rebirth, and newfound confidence. Just about always in that order.

How it feels when it works (and when it doesn’t)

In my experience, there’s been no correlation between how an infusion feels and how successful it is. I’ve had profoundly meaningful and pleasant infusions that did next to nothing; I’ve had frightening and elegiac infusions that changed me in lasting ways.

Post-infusion care and integration are every bit as vital to neural rewiring as the ketamine itself.

My gameplan for what I call the “afterburn” (the 24 hours post-infusion) is to drink plenty of water, eat plenty of food, get plenty of sleep, and avoid all of the following: calls, work, driving, decision-making, the news, deep thought, stress, alcohol, and tobacco.

While most infusions register some improvement, a handful have not–usually due to something sabotaging the post-infusion window. Booze. Bad sleep. Dehydration. Stress. The Buffalo Bills losing to the Kansas City Chiefs in the playoffs.

When ketamine works–and I was usually able to tell by day No. 2, if not sooner–it was obvious. I started incorporating healthier habits. I felt myself become kinder and more empathetic, clearer in thought and morality, more courageous and self-assured, more compassionate toward myself, and less reactive to slights or mistakes. I laughed often and more easily.

Most noticeably, I became more curious. Ketamine may not be a wonder drug, per se, but my elementary understanding of neuronal function and limited experience with other psychotropic medication has convinced me to believe that there may be no other substance that sparks wonder so subtly or effectively.

It’s the curiosity and wonder that have led me to believe that this is the “rewiring” in action. I was often reminded of the Overview Effect–a cognitive shift experienced by astronauts upon seeing the Earth in full from space for the first time. When they return from orbit, they report increased feelings of cooperation and collectivism and a kind of self-transcendence. They become more appreciative, empathetic, and kind. They change the way they show up.

So … does it work?

It’s been four years since I first explored ketamine treatment for my depression. Since then, we’ve endured a deadly global pandemic and a distressing decline in our social and political climates. There’s not enough ketamine in the world to cure what ails us collectively. There’s so much of that noise in the data – plus unrelated work, home, and life stressors – that I can’t tell you whether I’m “still depressed” or if the infusions were worth it.

In short, I think it was worth trying, but it also was no magic bullet.

What I can tell you is this: Ketamine made me a marginally better person. Clearer, kinder, more curious, and occasionally happier. At the same time, I recognized that ketamine is just one part of a bigger picture. Improving your mood requires diligent self-care and self-inquiry, the absence of significant personal and systemic challenges, robust relationships with people close to you, and the curiosity and enthusiasm required to keep learning and growing. Ketamine helps facilitate that final piece and only that final piece.

If that feels like an underwhelming appraisal of something that repeatedly simulates near-death experiences for $500 per hour, let me close with this anecdote. In 2019, I collected my ketamine notes into a 10,000-word essay I published on Medium. It became my most popular and critically lauded written work and earned me enough money and professional and public service opportunities – including writing this very article – to radically change my life. It wasn’t the chemical that changed me; it was what I did with the opportunity it granted me that did. I’ve learned, grown, changed, and evolved – maybe that’s all we can do. Maybe that’s the best we can do. I’ll take it.

The future of Alzheimer’s Disease drugs

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.