5HT+ Special Report: Alzheimer’s & Dementia Prevention

Today, 57 million people worldwide live with dementia, a disease that costs the world an estimated $1.3 trillion. Alzheimer's is the most common cause of dementia, accounting for 60-70% of cases. In the U.S. alone, 7.2M people over 65 live with Alzheimer's, and that number is projected to nearly double by 2050 📈 (!). 

The most common symptoms associated with Alzheimer’s are memory loss that disrupts daily life, difficulty planning or solving problems, trouble completing familiar tasks, confusion with time or place, and changes in mood, personality, or behavior. 

But Alzheimer’s doesn’t just steal memories—it was the 6th leading cause of death among U.S. seniors in 2022 😔, killing more people than breast and prostate cancer combined. It’s also a top driver of disability and dependency among older adults globally. Also, more than 11 million family members and unpaid caregivers provided ~18.4 billion hours of care for people with Alzheimer’s or other dementias in 2023, underscoring just how many this disease touches. 

The biggest risk factors are 🕰️ age (a person is more likely to get Alzheimer’s as they get older), ♀️gender (women are more likely to develop Alzheimer’s than men), and 🧬 genes (both familial and risk genes—like APOE4). Those risk factors can’t be changed—but others, like lifestyle and chronic health conditions, can.

For decades, two microscopic culprits in the brain have largely defined Alzheimer’s. First observed 🔍 nearly a century ago by Alois Alzheimer (yes, the disease is named after him), they remain the signature features of the disease today.

Believe it or not, we still don’t know what exactly causes Alzheimer’s disease 😳🧩. The leading theory is that amyloid buildup triggers a chain reaction that kills brain cells. As the disease progresses, the brain shrinks, especially in memory-critical areas, and neurons die off. Here’s a metaphor I like for all this: 

We can’t yet answer whether plaques and tangles cause the disease…or are just a byproduct of something deeper. I find it wild (and wildly infuriating) we don’t know this yet 😣. However, scientists are increasingly exploring contributors that may work alongside or independently of those classic features.

Bottom line: There’s no smoking gun 🙁 and Alzheimer’s likely results from a mix of factors. That’s also why a one-size-fits-all cure is so elusive—and why a holistic approach to prevention is gaining traction. More on that soon.

We’ve thrown an absurd amount of  money 💵 at trying to solve Alzheimer’s—NIH funding alone rose from $562M to $3.8B over the past decade. And still—99% of drug trials have failed. Between 2002 and 2012, 244 compounds were tested in 413 clinical trials for Alzheimer’s—and only one (memantine) gained FDA approval. One! 

These failures are frustrating—especially after billions invested. But any treatment that can slow the disease could save countless lives, not to mention billions of memories.

There was real hope in 2021 when the FDA approved Aduhelm—the first new Alzheimer’s drug in nearly two decades 📆. It cleared amyloid from the brain but didn’t show much cognitive benefit. The approval was highly controversial (the advisory panel voted overwhelmingly against it). Between safety concerns, a whopping $56K/year price tag, and restricted Medicare coverage, the drug quickly faded from use.

Today, only two ‼️ drugs are FDA-approved to target the underlying biology, and a few more help alleviate symptoms like memory loss or confusion. Here’s the current landscape 👇

To be clear: none of these are a cure. (I wish.) And frankly, none of these really make much of a difference overall (which makes them being prescribed pretty controversial). We just don’t have a real solution yet. Most experts now believe the answer won’t come from a single target (like amyloid), but a multi-pronged (and more holistic) approach. (There’s actually some drama around the “amyloid hypothesis” and scientific gatekeeping around it if you want to dig deeper).

This is all why new drug pipelines include anti-tau therapies to prevent tangles, anti-inflammatory drugs to calm overactive brain immune cells, and regenerative strategies like nerve growth factors or stem cell treatments. 

As of last year, there are 127 drugs in 164 clinical trials, and two-thirds target non-amyloid pathways. One oral drug with promise is ALZ-801, which targets toxic amyloid beta oligomers and is being tested specifically in people with two APOE4 genes. Researchers are also exploring vaccines and gene therapies that could one day help prevent or eliminate high-risk mutations like APOE4. 

After decades of tunnel vision, the field is finally zooming out—embracing a systems-level approach to treat (and maybe one day prevent) this disease. Let’s really hope there are some true breakthroughs soon.

But until then, prevention starts with us. 🤝

Many experts now think a significant chunk of Alzheimer’s cases could be tied to what’s called “modifiable factors.” A recent pilot study showed even patients with mild cognitive impairment who underwent a very intensive lifestyle change plan saw improved cognitive function after 6 months. That’s a big deal!

Basically, what we do (or don’t do) in our mid-life years can tilt the odds. So, while scientists chase innovative cures, we can use lifestyle interventions to support our brain health. This is the unsexy stuff that changes everything, annnd where I spend most of my time 😅. 

Here are the three levers that show up again and again in prevention research:

If there’s a single intervention nearly all Alzheimer’s experts agree on, it’s this: Move your body. Studies show that physical activity lowers dementia risk by 30-50% and can literally change your brain. Exercise also increases BDNF (brain-derived neurotrophic factor), a trophic factor associated with cognitive improvement. 

And you don’t have to run marathons! One study shows even 10K steps/day could reduce the risk of dementia by half, while another says increasing physical activity, even as little as five minutes/day, can reduce dementia risk. Resistance training matters, too. It helps maintain muscle (linked to metabolic health) and may promote the growth of new brain cells. Think of exercise as non-negotiable brain medicine.

Good sleep is like a brain rinse cycle. While studies are ongoing, some now believe quality sleep may help clear the brain of toxic proteins that eventually cause Alzheimer's. Cultivating good “sleep hygiene” means consistent bed and wake times, a dark, cool bedroom, limiting alcohol and caffeine (especially in the evening), and managing stress so it doesn’t keep you up.

Quality sleep also helps other factors that affect brain health, like metabolism and other cellular functions. Whereas, deficient sleep has been linked to higher dementia risk, including one study that found people who slept fewer than 5 hours a night were twice as likely to develop dementia (and to die 😬) as those clocking 6-8 hours. To be totally honest, this is my weak spot—and this research has officially scared me/freaked me out enough into doing more.

Food is brain fuel. And some diets protect it better than others. The Mediterranean diet and the MIND diet are both linked to cognitive health. One study even found that the MIND diet lowered Alzheimer’s risk by about 53% (!) compared to those who didn’t follow the diet closely. What they have in common:

And yes, this is basically the opposite of the average American diet. ☹️

Star players: Vegetables (especially green leafy vegetables), berries, whole grains, beans, nuts, fish, and olive oil.

Weak links: Red meat, sweets, cheese, butter/margarine, and fast/fried food.

Outside of these diets, green tea 🍵 has been shown to break apart protein tau tangles while salt 🧂 increases tangles. Basically think more tea, less takeout.

Though sleep, diet, and exercise are broadly seen as the interventions that could make the greatest impact, other promising levers are emerging. 

A true story: After my mom was diagnosed, I did the NYT Crossword Puzzle every single day for five years. Then I had kids. 😬

I know, it’s a lot—and don’t feel like you have to implement it all at once. Small shifts compound ✨. And even if Alzheimer’s still occurs eventually, patients who’ve led healthy lifestyles tend to have slower progression—a few extra years is no joke.

As science catches up, there’s a rising interest in brain-enhancing 💊 supplements. The term “nootropic” basically refers to anything that claims to boost brainpower ⚡️. Buuut supplements/nootropics are sorta the Wild West. Some ingredients are backed by real science. Most aren’t. And almost all lack large, legit human trials. 

It’s a blurry space—but then again, so is Alzheimer’s prevention. That’s why I’m still experimenting to see what helps me stay sharp. (This, by the way, is a good time to remind you: I’m not a medical expert—I'm just a deeply curious guy with a family history and 100 tabs open at all times.)

Through lots of digging (and tinkering), I’ve built a daily brain health stack. As a 5HT+ member, you get exclusive access to my fancy-schmancy Brain Health Vitamin & Supplement list 🙌 . But here’s a quick breakdown of what I take:

Others I’m into 🙂: Alpha GPC (but duplicative with Citocoline), Phosphatidylserine, and Rhodiola Rosea. 

Promising, still testing 🤔: PQQ, Alpinia Galanga Extract, blueberry extract (shown to improve cognitive function), and lemon balm. 

Less sold on 🫤: Ashwagandha (for these purposes) and Ginkgo Biloba (impressive, but has too many interactions with others). 

Fun fact: My obsession with getting an afternoon brain boost (and kicking out brain fog) drove me to start Fixie Dust 🤠, a fun new nootropic supplement brand that comes in the form of Pixy Stix-like packs. You’ll start hearing more about this really soon.

A decade ago, if you told your doctor you had a family history of Alzheimer’s and wanted to prevent it, you might’ve gotten a shrug 😔. Today, you’re more likely to get a referral—and a message of empowerment ✊. There are steps you can take, people you can see, and places to go. The prevention ecosystem is growing.

Yes, Alzheimer’s prevention clinics exist. One of the pioneers in this space is Dr. Richard Isaacson, who founded the first Alzheimer’s Prevention Clinic at Weill Cornell and Columbia. He’s been a driving force in showing lifestyle changes aren’t just feel-good advice—they can meaningfully delay cognitive decline, especially in high-risk patients.

His clinic pioneered the idea that prevention can and should be personalized, just like cancer or heart disease treatment. His clinic's results, published in the Journal of Alzheimer's Disease, showed participants who followed a personalized prevention plan saw slower cognitive decline and, in some cases, improvements in memory. (Other clinics also offer tailored prevention plans. Some I found were Kemper Cognitive Wellness, Re:Cognition Health, or MaxWell Clinic).

More institutions, like those below, are offering structured programs to help people take action:

Prevention support isn’t just clinical—it’s community-driven. Vibrant online forums and support groups are helping to grow awareness and drive progress. 

For decades, Alzheimer’s could only be definitively diagnosed after significant brain damage had occurred (often through cognitive tests and eventually autopsy). But imagine if we could spot the disease 10-20 years before symptoms—and intervene early.

Well, we’re actually on the cusp of a revolution in early detection with increases in inexpensive blood tests, digital cognitive monitoring, and other novel methods that can flag 🚩Alzheimer’s risk in asymptomatic people. This is one area we’re actually making progress in! Let’s look at a few: 

In what Eric Topol refers to as “one of the most exciting advances in neurology for decades,” there are now new blood tests that can detect brain changes with striking accuracy. These tests measure abnormal amyloid-beta and tau proteins in plasma, once only visible through spinal taps or costly PET scans. In some cases, they can identify early signs of Alzheimer’s years before symptoms appear. They’ve shown up to 94% accuracy when combined with age and APOE4 status. That’s wildly promising. 

Full disclosure: Despite my curiosity, I haven’t taken this blood test yet 😬. That’s mostly because I’m already motivated to live healthily, and knowing my current amyloid status wouldn’t change my approach. Yet, this testing might become routine in the next 5-10 years and I plan to add it to mine if so.

Fascinating work is happening using digital biomarkers. AI is being built to detect subtle changes in speech, typing patterns, or daily behaviors as early harbingers of cognitive decline. Smartphone apps might soon track how quickly you respond to messages or how steadily you walk, creating a “digital phenotype” of your brain health. I can definitely imagine a future where your devices could give you a nudge that it’s time to see a doctor—perhaps long before you (or your family) notice any memory slips. Like Inspector Gadget but for brain health.

The eyes are an extension of the brain, and new scans can visualize amyloid and other changes in the retina that might mirror what’s happening neurologically. So crazy, but so cool! This area is still experimental, but another promising sign of progress.

Ultimately, early detection gives us a fighting chance. We’re moving toward Alzheimer’s being a condition you can monitor, like blood pressure or blood sugar, and manage proactively. I’m very optimistic about this.

Of course, early detection naturally raises concerns and questions. Not everyone wants to know they have Alzheimer’s brewing, especially when there isn’t a cure/great solution yet. Then there’s also the issue of false positives or uncertain results 🫤. I respect that some friends in similar situations have chosen not to find out their APOE status. It’s a deeply personal decision—and one only you can make.

Watching a loved one fade—while still physically present—is truly one of the cruelest parts of this disease. And it’s a strange thing: To grieve someone while they’re still alive. Psychologists call it "ambiguous loss" when someone is gone and not gone. Unlike typical grief, there’s no clear point of closure. No funeral, no finality. The mourning lingers, and it complicates your ability to move forward. 

I’ve grieved my amazing Mom for a decade. Though she’s still here physically, I can’t move on. Neither can my Dad or brother. And it brings up impossible questions like what do you owe someone who’s no longer themselves? It’s a question my Dad lives with every day and one I hope my wife won’t ever have to ask.

Sometimes, this feeling overlaps with what’s called "disenfranchised grief" 😶—when your mourning isn’t fully recognized by others. Because technically, they’re still here. So, what are you mourning? But I can tell you firsthand seeing my mother become a stranger is a grief that deserves to be felt, to be seen. 

And you know…she was awesome at faking it, at first. We believed it—maybe out of fear, maybe out of hope. But the eccentricities kept piling up until, one day, it was over. She, or the version of her we knew, was gone. 😔 There were flashes—brief moments when she came back. Little sparks of recognition made it hard to argue she wasn’t still in there. But those moments are long gone now.

A more recent memory is the day my Mom met my first daughter. I’ll never forget how, when she looked at her, it was the same way she looked at a fork. It meant nothing to her. I share this because a future where someone doesn’t have to experience a moment like this is a future I want to fight for. 

Alzheimer’s doesn’t just erase memories, after all. It unravels identity, personality, and the very relationships that define us. It forces us to face existential questions about what makes us us. Is someone still themselves if they no longer remember who they are—or who you are? Some say yes. Others say Alzheimer’s hijacks the person entirely. I have wrestled with this, and I still really don’t know. 🤷‍♂️

What I do know is that I want to be there—for my wife, my kids, and their memories of me 🫶. Not just physically, but fully present. I see every single choice as a promise to my family, to what I leave them with. It’s what drives my obsession with prevention. 

Unlike Bryan Johnson, I don’t want to live forever, but I do want to stay as “me” as long as humanely possible. And ultimately, that’s why I fight. Because love is worth remembering—and being remembered. ❤️

If the last few years have shown us anything, it’s that progress against neurodegeneration is possible. We’re entering a new phase in the fight 🚀—one that includes better prevention techniques, more targeted drug therapies, and a clearer understanding of how to intervene earlier.

On the horizon: gene therapy, AI headbands and wearable devices that can deliver real-time brain health insights, and neuroprosthetics designed to restore lost cognitive function. While much of this is still experimental, it’s progress 👍. 

Health startups are also trying to tackle multiple ends of the Alzheimer’s problem. One where I’m a consultant at, Isaac Health, is an in-home memory clinic for brain health and memory issues. 

Then there’s public health efforts—like improving nutrition, education, and reducing air pollution—which also have a role to play. Education, in particular, has been associated with lower dementia risk.

But getting closer to that future requires destigmatization. 

Alzheimer’s is not a dark secret—it’s a widespread challenge we can face with openness and proactive effort. Just look at Chris Hemsworth (yes, Thor). He didn’t hide it after learning he carries two copies of APOE4. Rather, he paused his career, took action, and spoke publicly about the steps he’s taking. Honestly, talk about being a real life superhero. 🦸

Ultimately, we have to wonder: Is a world without Alzheimer’s disease possible? Maybe. Maybe Alzheimer’s will go the way of polio—not totally gone, but dramatically reduced. 

Imagine if we diagnosed people 15 years before symptoms and then started them on a combination of therapies (say, a monthly antibody infusion, a daily oral drug that targets tau, a strict lifestyle regimen, and a vaccine every few years). Together, these could delay onset until the very end of life, so people still die, yes, but with their memories largely intact. That’s not guaranteed. But it’s no longer pure fantasy. And maybe it’s naive or overly optimistic, but I believe we can get there. 🤞

I’ve had bits and pieces of this story spread between Google Docs, bookmarks, and memories, and it feels good to bring it all into one place and hopefully give someone else a chance to fight back. Still, as said up top (or about 4K words ago 😅), this topic can be extremely lonely, so I’m grateful you’re here. I also hope you’ve found this debrief valuable, whether Alzheimer's has touched your life or not (FWIW, I hope it never does). 

(And, of course, should you need additional support, the Alzheimer’s Association has a free 24/7 helpline: 1-800-272-3900. Call anytime. Middle of the night panic or midday spiral—they’ve got you.)

While I don’t have all the answers, I do have a plan. So if you’re curious about the specific steps I’m taking, here’s what my prevention plan looks like now (based on years of researching this stuff). 💪🧠

👋 Who are you again? I’m Derek Flanzraich—founder of two venture-backed startups in Greatist (👍) and Ness (👎). I’ve worked with brands like GoodRx, Parsley, Midi, Ro, NOCD, and Peloton. I now run Healthyish Content, a premium health content & SEO agency (among other things).

Every Thursday, I share 5 health things I feel strongly about so you can live healthyish. And this is a special edition: One health topic, 10 parts, for 5HT+ members only. (As a reminder: I’m more your friend with health benefits. None of this is medical advice.)