GreyMatters
Educational articles, BetterBrain resources, latest in brain health, and news about us. Written for you, with expertise (and love).
An 11-country trial tested brain health advice against structured support
The same brain health advice produced very different results
Most people already know the broad advice for protecting their brain. Exercise regularly. Eat well. Manage blood pressure and blood sugar. Stay socially and mentally engaged. Get enough sleep.
The harder part is following through consistently, especially when work gets busy, routines change, motivation fades, or the original plan does not fit your life very well.
A two-year randomized trial across eleven Latin American countries has now put a number on how much that harder part is worth. Both groups worked on the same broad areas of brain health. One group received ongoing coaching, supervision, and regular group meetings. The other received health education and general recommendations. After two years, the structured group showed 55 percent greater improvement in overall memory, thinking, and reasoning.
The trial, called LatAm-FINGERS, was published in The Lancet and presented at the Alzheimer's Association International Conference.
What the trial tested
The study included 1,065 older adults who were at elevated risk of cognitive decline but did not have dementia. It ran across twelve sites in eleven countries and followed participants for two years.
Both groups worked on the same broad areas of brain health, including physical activity, nutrition, cognitive training, social engagement, and management of cardiovascular risk. The difference was the amount of structure surrounding the work.
The flexible group, 526 participants, attended four meetings over two years. They received health education and general recommendations, but no ongoing coaching or supervision.
The structured group, 539 participants, received supervised exercise, nutrition counseling, cognitive training, cardiovascular risk monitoring, ongoing coaching, and 38 group meetings that provided social connection and accountability.
In other words, the trial was not testing whether lifestyle matters for the brain. That question has been asked before. It was testing how much the way a program is delivered can change the results it produces.
What happened
After two years, the structured group showed 55 percent greater improvement in overall memory, thinking, and reasoning than the more flexible group. They also had greater improvements in executive function and processing speed.
Both groups were working on their brain health, and both improved. The structured group simply improved much more.
That makes the finding more interesting than a comparison between doing something and doing nothing. The broad recommendations were similar. What changed was the frequency of contact, the level of supervision, and the support participants received while putting those recommendations into practice.
Because participants were randomly assigned to the two groups, differences in motivation or baseline health are less likely to explain the result. The structured program itself appears to have contributed to the additional cognitive improvement.
Heather Snyder of the Alzheimer's Association, commenting on the results at the conference, put it simply: "A key message from this study is that structure and social support matter."
The finding builds on the original FINGER trial in Finland, which found that a multidomain lifestyle program could help protect cognitive function in older adults at risk of decline. LatAm-FINGERS took that model and adapted it to local cultures, diets, and habits rather than importing it unchanged, which matters for anyone wondering whether these programs travel.
Read the full LatAm-FINGERS study
What structured support actually does
A brain health plan can look simple on paper and still be difficult to carry out.
A person may leave an appointment intending to exercise four times a week, improve their sleep, change their diet, take several supplements, and reduce stress. Every recommendation may be reasonable. The problem is that seven reasonable priorities are still seven priorities competing with the rest of life.
A few weeks later, the easiest habits are sometimes still happening. The more inconvenient ones have started to disappear, which is where structured support comes into play. It creates a regular opportunity to review what happened, understand why something did not work, and adjust the action plan before one missed week becomes a habit that has quietly been abandoned.
Sometimes the person needs accountability. Sometimes the goal was too ambitious. Sometimes the recommendation needs to change because of travel, an injury, family responsibilities, or a demanding period at work.
The goal is not to follow the original plan perfectly. It is to keep adjusting the plan until it works in real life.
The question the study leaves open
LatAm-FINGERS compared a structured, intensive program with a more flexible, self-guided version focused on the same broad areas of brain health. It did not test whether a personalized action plan works better than a generic one. That is a separate question, and an important one.
Two people can receive the same list of brain health recommendations and have very different needs. One person may need to focus on blood pressure. Another may need to address poor sleep, low cardiovascular fitness, insulin resistance, or a nutritional deficiency first. The markers that shape brain health sit across sleep, metabolic health, cardiovascular health, inflammation, and nutrition, and they do not line up the same way in any two people.
A useful brain health system needs to answer two questions. What matters most for this person, and what will help them keep doing it?
Personalization helps determine the priorities. Structure helps turn those priorities into sustained action.
How BetterBrain approaches both
BetterBrain is one connected system that brings together brain-relevant health information, a personalized action plan, and continued support.
There are two ways to start.
Some people begin with Blueprint, which uses more than 50 brain-relevant biomarkers, cognitive testing, health history, and lifestyle information to identify the areas that matter most for their brain health, with a nurse coach to walk through what the results mean. Instead of receiving a broad list of everything they could improve, they get a personalized action plan ranked by impact.
Others begin with the Coaching Program, where a dedicated brain health coach helps build the action plan, checks in on progress, and adjusts it when life gets in the way. Coaching is often fully covered by insurance, and many commercially insured clients pay nothing out of pocket.
Both starting points lead toward the same goal: a smaller set of meaningful priorities, a realistic action plan, and enough continued support for that plan to last.
The bottom line
The LatAm-FINGERS trial moves the brain health conversation beyond whether lifestyle matters. It shows that the way lifestyle guidance is delivered can meaningfully change the outcome.
Advice alone leaves people responsible for setting priorities, creating a schedule, tracking progress, solving barriers, and knowing when to adjust the plan. A better delivery system does those things with them. It provides clear priorities, regular contact, accountability, opportunities to review progress, and a way to adapt when the original plan stops working. That support helps healthy actions continue long enough to produce meaningful results.
Personalization helps you choose the right actions. Structure helps you keep doing them.
How to Keep Your Brain Sharp at Any Age: 6 Lessons From Dr. Tommy Wood on Huberman Lab
Our Chief Science Officer, Dr. Tommy Wood, joined Andrew Huberman on the Huberman Lab podcast for a nearly three-hour conversation titled "Accelerate Learning & Increase Cognitive Capacity." His core message: your brain keeps adapting to whatever you ask of it, at 40 and at 75. Staying sharp is less about your age and more about whether you keep giving your brain new, challenging inputs, move your body before and around mental work, eat a high-quality overall diet, and test your biomarkers instead of guessing at supplements.
Here are the six takeaways we think are most worth acting on, plus where to start if you want to put them into practice.
Does aging itself cause cognitive decline?
Not in the way most people assume. According to Wood, aging itself is not the primary driver of decline. Your brain keeps the capacities you use and prunes the ones you stop using, so much of what we call age-related decline comes from no longer giving the brain new, challenging inputs. Encouragingly, he notes that mental processing speed tends to hold steady until around age 60.
That reframing matters. If decline is largely about disuse rather than age, then the inputs you choose, at any age, are levers you control.
What activities actually keep your brain sharp?
The activities that build cognitive capacity share three traits: they are new, hard, and ideally social.
Crosswords and sudoku, Wood points out, are more relaxing than challenging. They exercise skills you already have. To actually build capacity, pick something that stretches you and mixes movement, thinking, and other people:
- Dancing has the best evidence, ballroom and square dancing especially
- Ball sports and martial arts
- Learning a language
Part of the trick is getting comfortable being a beginner. The discomfort of making mistakes is not a sign you picked the wrong activity. It is what drives the learning.
Do you need to be in a flow state to learn?
No. Real learning, and even peak performance, often happens in what athletes call a clutch state, where the work still feels like hard work.
What matters more is structure. Hard mental work is really only sustainable in 20 to 30 minute focused blocks, so work in chunks and protect them from distraction. Even having a phone in the room carries a cost to focus.
How does exercise improve learning and memory?
Wood describes exercise as two brain tools in one:
- In the moment: a short 20 to 30 minute jog or strength session right before mental work sharpens learning during that session.
- Over time: harder aerobic work, like intervals, builds the hippocampus and supports memory, while resistance training builds the brain's white matter and supports decision-making.
The practical answer to "cardio or weights for brain health?" is both, and if you can, schedule some of it right before your most demanding mental work.
What should you eat, and should you take supplements?
On diet, whole-food patterns like the Mediterranean and MIND diets have the best evidence, and it is overall diet quality, not any single food, that matters.
On supplements, Wood's advice is to test your levels rather than guess, because the standard "normal" lab range is not the same as the optimal one. His clearest example: omega-3 and B vitamins only work when you have both. That interdependence is exactly why we measure homocysteine and other brain-specific biomarkers in Blueprint rather than blanket-recommending a supplement stack.
For supplements with modest, real support, he points to creatine and a basic omega-3 plus B-vitamin stack. Our picks in those categories, including Advanced DHA, Thorne Creatine, and MethylAssist, are all in the Picks library, and Picks is now HSA/FSA eligible through our partnership with TrueMed.
What else protects long-term brain health?
Some of the biggest protections are indirect. Blood pressure, cholesterol, hearing, and metabolic health all shape long-term brain health. Avoiding serious illness matters too, because cognition tends to step down after a major sickness rather than declining smoothly.
One finding Wood flags as worth watching: the shingles vaccine has been associated with lower dementia risk across several large studies.
Where to start
You do not need a perfect routine or new technology. The conversation points to a short list: work on something hard and a little new, move before mental work, get real sleep, and test before you supplement.
That last step is where BetterBrain can help. Blueprint covers the testing, 50+ biomarkers plus cognitive testing and a 1:1 consultation to walk through your results, for $89 with insurance. And if you finish your results thinking "okay, but what should I actually do," that is what our 12-week Coaching Program is for. 92% of eligible customers pay $0 with insurance.
If you want to go deeper, listen to the full episode, and check out Tommy's new book, The Stimulated Mind: Future-Proof Your Brain from Dementia and Stay Sharp at Any Age, which covers the same ground in more depth through his 3-S model: challenge the brain, feed it, and let it recover.
Frequently asked questions
At what age does cognitive decline start?
Later than most people think. Wood notes that mental processing speed tends to hold steady until around age 60, and that much of what we attribute to aging actually reflects reduced challenge. The brain keeps what you use and prunes what you stop using, at any age.
Are crosswords and sudoku enough to keep your brain sharp?
Probably not. Wood describes them as more relaxing than challenging, since they exercise skills you already have. To build new capacity, choose activities that are new, hard, and social, like dancing, ball sports, martial arts, or learning a language.
What is the best exercise for brain health?
Both aerobic and resistance training, for different reasons. Harder aerobic work like intervals builds the hippocampus and supports memory, while resistance training builds white matter and supports decision-making. A 20 to 30 minute session right before mental work also sharpens learning in the moment.
Should I take supplements for brain health?
Test first. Standard "normal" lab ranges are not the same as optimal ranges, and some nutrients depend on each other. Omega-3 and B vitamins, for example, only work when you have both, which is why measuring biomarkers like homocysteine beats guessing. Creatine and a basic omega-3 plus B-vitamin stack have modest, real evidence behind them.
Grey Matters: See the research behind every recommendation
Hey there,
There's a lot of brain health advice on the internet, and most of it comes with the same problem: no way to tell where it came from or if it's trustworthy. Someone tells you sauna is good for your brain, or that you should be lifting, or that omega-3s matter, and you're left to either take it on faith or go digging through PubMed yourself. Most people, reasonably, just take it on faith.
We've never loved that, because trust in health advice should be earned, not assumed. So we did two things worth telling you about.
The Content Library
First, if you haven't spent time in the Content Library inside your dashboard, it's worth a look. It's a growing, curated collection of the best brain health content we can find: videos, podcasts, articles, and clips, pulled from people who actually know what they're talking about. Think Andrew Huberman on light and sleep, Rhonda Patrick on sauna and exercise, our own CSO Tommy Wood on reducing cognitive decline, and a lot more.
You can search it, filter by format, and save what you want to come back to. And BeBe can point you to the right thing for wherever you are: if you ask about sleep, it can hand you the specific episode worth your time instead of making you wade through everything. It's the difference between a search engine and a good friend who's already done the reading. If you're not a BetterBrain client yet, you can access the Content Library for free with a Self-Directed account.
Technique Spotlight
The studies behind your plan
This is the part we're most excited about. Every technique and recommendation in your BetterBrain plan is now linked to the actual research behind it, the specific studies connected to the specific practice, biomarker, or system they support. When BeBe or your coach suggests something, you can trace it straight to the evidence and see how strong it is.
This was a big project and it brings roughly 1,500 studies into the app, mapped to the techniques and markers they relate to. Weak or unsupported studies were deliberately left out, so what's linked is the evidence we'd actually stand behind.
Here's why that matters. Not every recommendation carries the same weight. Some are backed by large randomized trials, others by smaller or observational work, and you deserve to know which is which. Linking the studies keeps us accountable to the evidence and lets you make informed decisions instead of just following instructions. It's the same standard we hold ourselves to internally: when a new study comes out, we read it, assess it, and only fold it into what we recommend if it holds up.
How this relates to brain health
Brain health is a field with real science and a lot of noise, and the two are easy to confuse. We try to stay on the science side of that line and be honest about what's solid, what's promising, and what's still an open question. Making the research visible is that principle made concrete. If we recommend it, you should be able to check it.
If you want to explore, open a technique and scroll to the bottom to see the relevant studies or ask BeBe why it recommends any technique in your plan, and follow the research yourself.
And if you're reading this as someone who hasn't started with us yet: this is what BetterBrain is, evidence-based brain health guidance you can verify, not wellness advice you have to trust blindly. BetterBrain coaching is covered at $0 for 92% of approved clients. See if you're covered.
Know someone who might benefit from BetterBrain?
Share this referral link and they'll get Essentials labs (50+ biomarkers) for just $39 (normally $89), plus access to $0 coaching with insurance.
You Can Now See the Studies Behind Every BetterBrain Recommendation
There's a lot of brain health advice on the internet, and most of it comes with the same problem: no way to tell where it came from or whether it's trustworthy.
Someone tells you sauna is good for your brain. Or that you should be lifting. Or that omega-3s matter. And you're left to either take it on faith or go digging through PubMed yourself. Most people, reasonably, just take it on faith.
We've never loved that. Trust in health advice should be earned, not assumed. So we did two things worth telling you about.
The Content Library: curated, not crowdsourced
If you haven't spent time in the Content Library inside your dashboard, it's worth a look. It's a growing, curated collection of the best brain health content we can find: videos, podcasts, articles, and clips from people who actually know what they're talking about.
Think Andrew Huberman on light and sleep. Rhonda Patrick on sauna and exercise. Our own Chief Science Officer, Dr. Tommy Wood, on reducing cognitive decline. And a lot more.
You can search it, filter by format, and save what you want to come back to. And BeBe, our AI assistant, can point you to the right thing for wherever you are. Ask about sleep, and it hands you the specific episode worth your time instead of making you wade through everything. It's the difference between a search engine and a good friend who's already done the reading.
Not a BetterBrain client yet? You can access the Content Library for free with a Self-Directed account.
The studies behind your plan
This is the part we're most excited about.
Every technique and recommendation in your BetterBrain plan is now linked to the actual research behind it: the specific studies connected to the specific practice, biomarker, or body system they support. When BeBe or your coach suggests something, you can trace it straight to the evidence and see how strong it is.
This was a big project. It brings roughly 1,500 studies into the app, each mapped to the techniques and markers it relates to. Weak or unsupported studies were deliberately left out, so what's linked is the evidence we'd actually stand behind.
Why evidence strength matters
Not every recommendation carries the same weight. Some are backed by large randomized controlled trials. Others rest on smaller or observational work. You deserve to know which is which.
Linking the studies does two things. It keeps us accountable to the evidence. And it lets you make informed decisions instead of just following instructions.
It's the same standard we hold ourselves to internally: when a new study comes out, we read it, assess it, and only fold it into what we recommend if it holds up.
Why this fits how we think about brain health
Brain health is a field with real science and a lot of noise, and the two are easy to confuse. We try to stay on the science side of that line and be honest about what's solid, what's promising, and what's still an open question.
Making the research visible is that principle made concrete. If we recommend it, you should be able to check it.
How to explore
Open any technique in your plan and scroll to the bottom to see the relevant studies. Or ask BeBe why it recommends any technique in your plan, and follow the research yourself.
And if you're reading this as someone who hasn't started with us yet: this is what BetterBrain is. Evidence-based guidance to sharpen your brain health now and reduce dementia risk long-term, backed by research you can verify rather than wellness advice you have to trust blindly. BetterBrain coaching is covered at $0 for 92% of approved clients. See if you're covered.
Bottom line
The Content Library puts the best brain health content in one curated place. And every technique in your plan is now linked to the real research behind it.
Trust in health advice should be earned. Now you can check ours.
How Chronic Stress Shrinks Your Brain, and How to Reverse It
Chronic stress does more than affect your mood. Sustained cortisol exposure physically shrinks the hippocampus, your brain's primary memory center. The encouraging part: this is reversible. In controlled neuroimaging studies, eight weeks of mindfulness practice increased gray matter in the hippocampus and reduced it in the amygdala, the brain's threat-detection center. Managing stress is one of the most accessible ways to protect your long-term cognitive health.
Stress is easy to file under "quality of life" rather than "brain health." The neuroscience tells a different story, and it's a hopeful one, because the same biology that makes chronic stress harmful also makes it one of the most modifiable risks you can act on.
Below, we cover what chronic stress does to the brain, the landmark study showing mindfulness can reverse it, the techniques that actually work, and how to measure your progress.
What does chronic stress do to your brain?
When your brain perceives a threat, it releases cortisol. In short bursts, this is helpful, it sharpens your response to a genuine challenge. The problem is sustained elevation.
Under chronic stress, prolonged cortisol exposure becomes toxic to neurons, and the hippocampus is especially vulnerable because it is packed with cortisol receptors. Over time, that exposure causes the neural branches that let brain cells communicate to shrink. The downstream effects are measurable: reduced hippocampal volume, fewer new brain cells, and impaired memory.
This matters beyond day-to-day forgetfulness. Hippocampal shrinkage is one of the earliest detectable structural changes in Alzheimer's progression, and chronic psychological stress is now recognized as a modifiable dementia risk factor in its own right. In other words, stress sits on the same biological pathway as accelerated cognitive aging, which is precisely why acting on it has such a high return.
Can mindfulness reverse stress-related brain changes?
Yes, and the evidence comes from before-and-after brain imaging, not self-report.
In 2011, researchers at Harvard-affiliated Massachusetts General Hospital published a landmark neuroimaging study. Using MRI, they measured gray matter density in healthy adults before and after eight weeks of mindfulness practice. Participants showed measurable increases in gray matter in the hippocampus and in regions involved in learning and emotional regulation. At the same time, gray matter in the amygdala, the brain's primary stress and threat-detection center, decreased. A control group who did not practice mindfulness showed none of these changes.
The design is what makes it compelling. This was not a comparison of lifelong meditators against non-meditators, where genetics or lifestyle could explain the difference. It was imaging of the same brains, across just eight weeks of practice. You can read the full study here.
How does stress management protect the brain?
Mindfulness and related practices work through a few overlapping mechanisms. They reduce cortisol output, calm the amygdala's threat response, and lower the chronic, low-grade inflammation associated with sustained stress. These are the same pathways implicated in accelerated cognitive aging, so quieting them protects the brain on more than one front at once.
The practical implication is freeing: you do not need the "perfect" technique. You need to move these levers consistently, and there is more than one way to do that.
What stress management techniques actually work?
Different techniques reach the same biology through different doors, which means you have options. These are the Essential, evidence-based interventions to start with:
- Slow, deep breathing. Controlled breathing activates your parasympathetic nervous system, your body's "rest and digest" mode. Even a few minutes measurably reduces cortisol and heart rate. For many people this is the easiest entry point.
- Mindfulness meditation. The technique behind the brain-imaging study above. Consistent practice, even 8 to 10 minutes daily, produces measurable effects on stress hormones and self-reported stress within a few weeks.
- Nature exposure. Time in natural environments is associated with lower cortisol, lower blood pressure, and improved mood. The effect appears to be dose-dependent, so more time outdoors tends to help more.
- Social support. Strong social connections help buffer the brain against the effects of stress.
How do you start a 10-minute mindfulness practice?
You do not need a cushion, an app, or a quiet mind. Here is the whole practice:
Find a quiet spot and sit comfortably. Bring your attention to the physical sensation of your breath, the air moving in and out. Your mind will wander. That is not failure, that is the exercise. Each time you notice it drifting and bring it back, you are doing the rep that builds the skill. There is no perfect posture and no requirement to empty your mind. Just ten minutes of practicing the return.
A note on getting started: Don't overthink which technique to begin with. If sitting meditation feels like a stretch, start with a few minutes of slow breathing or a walk outside. The research is clear on this point: the technique that protects your brain is the one you will actually do.
How can you track stress and its effects on the brain?
You can't feel your inflammation dropping, but you can measure it. Chronic stress shows up in bloodwork as elevated hs-CRP, one of the same inflammatory markers associated with cognitive decline. When a stress-management practice starts working, that number moves, and lab panels let you watch it happen.
The effects ripple outward from there. Sleep quality typically improves within weeks of consistent practice, and better sleep gives your glymphatic system, your brain's overnight waste-clearance crew, more time to do its job.
This is what makes stress management such a high-leverage intervention. It rarely works alone. Better stress regulation improves your sleep, better sleep amplifies the benefits of exercise, and lower inflammation makes anti-inflammatory nutrition work harder. Pull one lever, and the whole system responds.
The bottom line
Chronic stress physically changes the structure of your brain, and mindfulness and related practices can measurably change it back. You don't need to overhaul your life to benefit. Ten minutes of breathing or meditation, a walk outside, or time with people you care about all move the same biology. Start with whatever feels easiest, stay consistent, and let the results compound.
If you're working with a Brain Health Coach, the De-Stress section of your protocol is a natural starting point.
Ready to build a personalized stress management practice? Check if your insurance covers coaching.
Frequently asked questions
Does stress really shrink your brain?Yes. Sustained cortisol exposure from chronic stress is associated with reduced hippocampal volume, the brain region responsible for memory. It also reduces the formation of new brain cells and impairs memory over time.
Can you reverse brain changes caused by stress?Evidence suggests you can. In a 2011 MRI study, eight weeks of mindfulness practice increased gray matter in the hippocampus and decreased it in the amygdala in the same participants, changes not seen in a non-practicing control group.
How long does it take for mindfulness to change the brain?Structural changes were measurable after eight weeks of practice in controlled imaging studies, and effects on stress hormones and self-reported stress often appear within a few weeks.
What is the best stress management technique for brain health?There is no single best technique. Slow breathing, mindfulness meditation, nature exposure, and strong social connection all work through overlapping pathways. The most effective one is the one you will do consistently.
Is chronic stress a risk factor for dementia?Chronic psychological stress is now recognized as a modifiable dementia risk factor. Hippocampal shrinkage, which stress contributes to, is one of the earliest structural changes seen in Alzheimer's progression.
Grey Matters: June is Brain Awareness Month: a friendly reminder
A few reminders worth repeating
The fundamentals matter. Movement, sleep, nutrition, and social connection show up in the research again and again, and the earlier you start working on them, the more they compound.
But the fundamentals are just the starting point. Brain health is also deeply individual, and what moves the needle most for one person may not be what moves it for you. Depending on your biology, your genetics, your biomarkers, and your specific risk factors, the right plan might involve targeted supplementation, hormone or metabolic interventions, cardiovascular work, cognitive training, or addressing things like sleep apnea or inflammation. That's exactly why knowing your baseline matters so much. It turns a generic checklist into a plan built around you.
What our members are saying
"I put off getting tested for years because I figured there was nothing I could do. BetterBrain showed me exactly where I stood and gave me a plan. I wish I'd started sooner." — John O.
"Having a coach who actually checks in made all the difference. I've never been this consistent with my health." — Caroline T.
"Knowing my numbers took away the fear. Now it just feels like something I'm in control of." — Sandra W.
Consider this your friendly nudge
If brain health has been on your mind, this is a good month to act on it. Getting started is simple, much of it may be covered by insurance, and your future self will thank you.
And if you've already started on your BetterBrian journey consider forwarding this to a friend to help them take that next step.
Share this referral link and they'll get Essentials labs (50+ biomarkers) for just $39 (normally $89), plus access to $0 coaching with insurance.
Get immediate insights with a 3 minute assessment
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Harnessing Heart Rate Variability for Brain Health
The intricate dance between our heart rate and brain function is more influential than we might think. Recent studies reveal that heart rate variability (HRV)—the measure of variations between individual heartbeats—affects our brain health, decision-making abilities, and even our emotional regulation. HRV is a physiological metric that we can train ourselves to improve, and its connections to the brain make HRV training a promising technique for dementia prevention and enhancing cognitive function.
Understanding the Heart-Brain Connection:
While your heart rate is the average number of beats per minute, HRV is the difference in length between individual heartbeats.
HRV is not just a measure of heart health - it reflects the health and balance of the autonomic nervous system (ANS), which is responsible for involuntary body functions. In particular, HRV serves as a key indicator of the interaction between the two components of the ANS: the sympathetic (fight or flight) and parasympathetic (rest and digest) nervous systems. Interestingly, there is a two-way feedback system between these nervous systems and the heart. The signals from the sympathetic and parasympathetic influence heart rate, and heart rate regulates the balance of these two systems. By exerting an influence on the ANS, heart rate variability helps regulate emotions and stress responses. In general, higher HRV is associated with better control over decision-making processes, emotional responses, anxiety, and social behaviors1.
Booting your HRV
Common HRV training protocols call for biofeedback, which is a fancy way of saying you need a sensor to measure your heart rate variability so you can improve it. HRV training involves guided exercises such as paced breathing while looking at real-time heart rate data to learn to consciously control heart rate variability. This is what makes it different from techniques like yoga or meditation - their focus is commonly to achieve a balanced state, whereas the goal of HRV training is to modulate physiological responses.
This technique not only promotes a balanced state but also has long-lasting effects on both mental and physical health. Thanks to the heart-brain connection, HRV training leads to improved emotional regulation and stress management. Although different training regimens exist, just five minutes of HRV training twice a day can significantly enhance control over the heart and reduce anxiety levels during stressful periods2. Critically, the benefits of HRV training extend far beyond mood and feeling: they also correlate with enhanced executive functions like planning, problem-solving, and resisting unhealthy impulses1. In fact, the benefits of this training can persist, with improvements seen even 12 weeks after stopping the training1.
Tying back to dementia
Thanks to its influence on stress response, cognitive function, healthy behaviors, and cardiac health, it’s no surprise that higher HRV is associated with stronger resilience against cognitive decline2,3. Since the simple daily practice of HRV biofeedback training can improve your HRV, we can think of it as a valuable tool to help delay the onset and progression of dementia. It's a clear testament to the power of our bodies' interconnected systems, and a reminder that taking care of our heart is as much about our mind.
Where to start with HRV training
- Choose a tracking device: the first step is to make sure you have the right equipment to measure your heart rate variability. Because you are measuring the time between individual heartbeats, you need a particularly sensitive device. Although some common wearables like the Apple watch or Whoop claim to measure HRV, it’s better to opt for a specialized chest strap like the Polar H10 which can connect to your other wearables.
- Visualize your data: once you have a solid device, use an app like Elite HRV or Welltory (both of which have a free version available) so that you can visualize your HRV in real time. These apps also come with a wealth of additional insights that can help you fine tune your training.
- Start training: you can find guided training sessions either through apps like Elite HRV or through online courses provided by organizations like the HeartMath Institute. YouTube also has a number of guided HRV routines you can try, such as this one from the Huberman Lab show.
- Learn more: The Peter Attia Drive podcast has an episode that dives deep into HRV so you can learn more about how it works and how it can help you.
Metabolic Syndrome as a Gateway to Dementia
It’s a well-known fact that Alzheimer’s disease is closely linked to metabolic health, to the point that some experts have begun to refer to it as Type III Diabetes. But what many people don’t know is that poor metabolic health is a strong risk factor for dementia long before it progresses to diabetes, even for people without a family history.
Decoding metabolic syndrome
Before you get diagnosed with diabetes, your body goes through a number of changes. Cells in your body become desensitized to insulin, which usually tells them to absorb sugar from your bloodstream. This results in chronically elevated blood sugar and in turn starts causing problems for your heart, liver, brain, and other organs. This pre-diabetic phase is called metabolic syndrome, and it affects ~25% of adults worldwide, including 40% adults aged 60+ in the U.S. Most of them do not know that metabolic syndrome is a health risk.
Metabolic syndrome is diagnosed when an individual has three or more of the following:
- High triglycerides (≥150 mg/dL)
- Elevated blood pressure (≥130 mmHg systolic or ≥85 mmHg diastolic) OR use of antihypertensive medication
- High fasting glucose (≥100 mg/dL OR use of glucose lowering medications)
- Low HDL cholesterol (<40 mg/dL in men; <50 mg/dL in women OR use of lipid-modifying medication)
- Abdominal obesity (waist circumference ≥102 cm for men and ≥88 cm for women)
It’s worth noting that hemoglobin A1c (HbA1c), a common marker for diabetes, does not feature on this list. Although a doctor won’t use A1c to diagnose metabolic syndrome, it’s still an important marker to keep track of your metabolic health.
Connecting metabolic syndrome to brain health
A large retrospective study1 analyzed data from 175,000 participants over a period of 15 years. Participants were aged 60+ and represented a variety of sociodemographic, lifestyle, and genetic backgrounds. With regards to the metabolic syndrome diagnosis criteria listed above, the study found that:
- Having three conditions increases dementia risk 12%
- Having four to five conditions is associated with an even stronger risk
- The link between metabolic syndrome and dementia is particularly strong in individuals who do not carry the APOE ε4 allele (typically, these are individuals with a lower risk of dementia)
Taking action
The first step is to know where you stand. It’s important to establish a baseline by measuring metabolic markers in your blood and potentially using a continuous glucose monitor (CGM) to see how your blood sugar reacts to your daily habits. This will help you make an informed decision on how to approach your metabolic health.
Metabolic health is strongly tied to your lifestyle - particularly your diet, physical activity, and sleep. There’s also several different drugs, like statins or ACE inhibitors, available to help manage symptoms. However, this post isn’t meant to serve as a meal plan or exercise sheet. Instead, we’ve put together a list of hacks that we think can make a difference even if you haven’t fully optimized your health.
- Drink a tablespoon of vinegar ~20 minutes before a meal. This helps avoid spikes in your blood sugar.
- Go for a walk after meals, especially if those meals are heavy on carbs (e.g., pasta, potatoes, bread). This helps your muscles absorb glucose more efficiently.
- Perform at least 10m of vigorous exercise per day. Raising your heart rate (e.g., through a short HIIT session) helps boost your insulin sensitivity, which keeps blood sugar low.some text
- Exercise is most effective at reducing blood sugar spikes when done within an hour before or after a meal
- Eat your carbs last. Start your meal by eating vegetables (which are high in fiber), then eating proteins and fats, and finally moving to carbs. This helps slow the absorption of sugar into your bloodstream, and in turn reduce sugar spikes.
Small steps add up
Although the hacks mentioned above aren’t meant to replace a healthy lifestyle, they can help you make an immediate improvement in your metabolic health and kickstart your dementia prevention efforts. Remember - working on your metabolic health isn’t just about preventing diabetes, it’s about safeguarding your cognitive health.
Actions to consider
- Measure your metabolic markers. Some of these you may get on your annual physical (e.g., HbA1c, HDL-C, LDL-C, glucose, triglycerides, insulin). Others are less common (e.g., Lp(a), ApoB). Most importantly, don’t settle for just ok. These markers are worth optimizing. All the tests mentioned above are part of the 50+ biomarkers tested during your BetterBrain Essentials blood draw.
- Consider using a CGM to get a more accurate view of how your body processes sugar. Using a CGM, you can observe the effects of what you eat and your lifestyle on your blood sugar in real time, which can help inform the daily choices you make. We love the Dexcom G7, which may be challenging to buy over-the-counter but can be bought for cheaper through Signos.
- Learn more about homocysteine on the Peter Attia Drive podcast #252. This episode covers a wide variety of topics related to brain health, and links many different risks and possible interventions to metabolic health.
Rapamycin: Revolutionizing Alzheimer's Prevention?
In the 1960s, researchers on Easter Island were investigating local indigenous peoples’ claims that the soil has healing properties. After testing various soil samples, the researchers isolated a small molecule they believed was responsible for the effects. They named it rapamycin5, after the traditional name for the island, Rapa Nui. Since its discovery, rapamycin has been used in various settings, from an antifungal agent to more recently a beacon of hope in anti-aging medicine. Additionally, it is showing promise in extending lifespan and preventing neurodegenerative diseases such as Alzheimer’s.
From anti-rejection med to longevity enhancer
The transition from an antifungal to a potential longevity drug has been intriguing. Rapamycin, approved in 1999 for its immunosuppressant qualities, is still commonly used in kidney transplants to prevent organ rejection. However, a 2014 study1 on older adults revealed a paradox: at much smaller doses, rapamycin boosted the immune response to flu vaccinations, despite their age-related weakened immune function. This unexpected enhancement suggests that rapamycin might have broader applications for disease prevention in older adults, potentially making it a valuable tool in combating age-related declines in the human immune system.
How rapa works
To understand how rapamycin works, it’s important to understand the molecule that it targets: a cellular receptor named mTOR. mTOR is present in nearly all cells in the human body and is responsible for mediating pathways that regulate cell growth, metabolism, and survival. Inhibiting mTOR completely is catastrophic - it prevents cells from making energy, eventually leading to their death. However, partial inhibition means that mTOR has a harder time forming a cluster with other proteins, which makes the cell act as if it's not getting enough food. This starts a process where the cell breaks down unneeded or damaged parts, like proteins that aren't folded correctly, which can otherwise impair the cell’s ability to function. This leads to improved cellular survival and resilience and is particularly relevant to brain health since one of the main features of Alzheimer’s is the accumulation of misfolded amyloid beta protein plaques in neurons.
The partial inhibition of mTOR therefore shows potential for slowing down the progression of Alzheimer’s disease and improving the survival rate of neurons. Animal studies2,3 suggest that rapamycin may help mitigate or improve many of the pathologies associated with Alzheimer's disease and potentially restore cognitive function.
Growing evidence yet limited human trials
While animal studies have robustly demonstrated lifespan and healthspan extensions—with remarkable outcomes like a 20-30% increase in the lifespan of mice4—human data remains scarce. The gap in human trials can be largely attributed to the fact that rapamycin use for longevity is considered “off-label”. This means that the Federal Drug Administration (FDA) has not yet approved rapamycin for this use, which diminishes incentives for comprehensive research funding. However, the evidence from animal studies across a variety of species strongly suggests a significant potential for rapamycin in anti-aging treatments.
Rapamycin’s mainstream use
As mentioned earlier, the FDA has only approved rapamycin for use as an immunosuppressant. It’s important to recognize that rapamycin use for longevity is still considered experimental and will not be reimbursed by insurance. Because the FDA hasn’t established guidelines around its use, there is no single accepted protocol for rapamycin dosage. Given the drug’s complex effects, the risk of experiencing side effects is real. Nonetheless,many individuals already use rapamycin “off-label” under the supervision of a physician for its longevity benefits. This is a perfectly legitimate use of the molecule, even though there is a lot we have yet to learn.
A promising option for the future
Rapamycin offers a compelling glimpse into the future of longevity and neuroprotection. Although its journey from a soil sample to a potential anti-aging miracle has been gradual, the promise it holds could change the landscape of preventive health. As research continues, both the medical community and potential users must weigh the benefits against the uncertainties of translating animal model successes to human health outcomes.
Learn more
Listen to the Peter Attia Drive episode on rapamycin to learn more about the molecule, its history, how it works, and the most recent evidence on its effects.
Unlocking the Power of Omega-3 Fatty Acids
As the quest for effective Alzheimer’s prevention continues, recent studies1,2 underscore the profound impact of dietary choices on our brain health. One nutrient class consistently at the forefront of neuroprotective research is Omega-3 fatty acids, particularly Docosahexaenoic Acid (DHA) and Eicosapentaenoic acid (EPA). In this post, we explore how integrating DHA and EPA into your diet can play a crucial role in reducing the risk of Alzheimer's disease.
Fatty acids explained1
DHA and EPA are a major omega-3 fatty acid predominantly found in fish oils. They are called essential fatty acids, meaning that the human body cannot produce them on its own, so they must come from dietary sources. Make sure not to confuse omega-3s (like DHA and EPA) with omega-6s. These are a different class of fatty acids typically found in vegetable oils and nuts. They are much more common in most diets, and can promote inflammation when consumed in excess.
DHA and EPA are particularly important because the molecules are building blocks for neurons. This means that maintaining healthy levels of DHA and EPA supports neuronal membrane integrity, promotes healthy synaptic activity, and mitigates inflammation within the brain. Long-term, these fatty acids have been shown to help preserve cognitive abilities and delay the onset of dementia1.
Clinical insights on Alzheimer’s prevention
A growing body of research points to a direct correlation between DHA and EPA intake and a reduction in the risk for Alzheimer's. Animal studies provide compelling evidence, showing that diets rich in DHA can significantly reduce the formation of amyloid plaques, which are closely linked to Alzheimer’s pathology1.
Furthermore, in human epidemiological research (research that investigates the distributions and determinants of health-related events in populations), increased consumption of DHA through dietary sources like fish has been associated with lower incidence rates of Alzheimer’s, suggesting its significant protective effect. One study3 found that people with the highest levels of DHA had a 49% lower risk of developing Alzheimer's disease compared to those with the lowest levels. This means that those in the top 20% were about half as likely to get Alzheimer's as those in the bottom 20%. Additionally, increasing DHA levels from the lowest group to the highest group was predicted to give an extra 4.7 years of life free from Alzheimer's disease.
Other studies have concluded similar results, showing a 47%5 reduction in risk, though there is debate about when this effect may occur. The consensus is that DHA supplementation is most effective when started early, before symptoms get classified as dementia6.
Increasing your omega-3 intake
There are two main ways to make sure you’re getting enough DHA and EPA - either making conscious dietary choices4 or taking supplements. From the diet side, fatty fish are an excellent source of omega-3s. Typical guidance recommends eating fish like salmon, mackerel, herring, or halibut at least 3 times per week. It’s worth noting that chia seeds and flax seeds are also excellent sources of omega-3s. Predatory fish like tuna are also good sources of EPA and DHA, but be careful not to consume them too often since they also contain high levels of mercury.
Fish oil supplements can be another great way to increase your intake of omega-3s - if you carry the APOE4 gene, supplementation is particularly important since you may have more trouble absorbing dietary omega-3s. However, it’s important to recognize that not all supplements were created equal. Specifically, not all brands will have the same purity of fatty acids, and not all will contain sufficient levels of DHA and EPA. Here are some things to look out for to make sure you are getting high quality fish oil:
- High amounts of DHA and EPA per serving (at least 500mg combined per serving)
- Minimal additives in the ingredients other than the oil and capsule contents
- Packaged in dark containers to protect the oil from light
A Step Towards Cognitive Longevity
Embracing a diet that includes adequate amounts of DHA and EPA can significantly contribute to brain health and potentially decrease the risk of Alzheimer’s. Start by evaluating your current dietary habits and consider how you might improve your omega-3 intake, ensuring your brain remains vibrant and healthy well into later life.
Where to get started
- Measure your blood omega-3 index to learn your current EPA and DHA levels. This is one of the 50+ biomarkers tested during your BetterBrain Essentials blood draw.
- Eat at least 3 servings of fatty fish (e.g., salmon, mackerel) per week, but make sure not to overdo your intake of predatory fish like tuna.
- Consider using fish oil supplements to increase your EPA and DHA intake. We recommend Carlson’s fish oil, which is available at a discount with a BetterBrain membership.
The Rise of Amyloid Blood Tests
The Landscape of Alzheimer's Biomarkers
When it comes to assessing the risk of cardiovascular disease, we have straightforward biomarkers such as ApoB (LDL) and blood pressure which can predict risk fairly accurately. However, the realm of neurodegenerative diseases like Alzheimer's is a lot more messy. For years, researchers and clinicians have depended PET scans or cerebral spinal fluid (CSF) for analyzing biomarkers like amyloid and tau proteins. But these procedures are expensive ($5-10K in the case of PET) or invasive (CSF requires a lumbar puncture), making them impractical for widespread use.
Enter blood amyloid tests, a relatively new but promising diagnostic aimed at solving this problem.
What Are Blood Amyloid Tests and How Do They Work?
As the name suggests, these tests measure the concentration of various amyloid beta proteins in the blood (and sometimes tau as well) as a proxy for amyloid deposition in the brain. While the scientific community continues to debate whether amyloid pathology is a root cause of Alzheimer's disease or merely a symptom of other underlying brain pathologies, there is a clear association between the extent of amyloid presence in the brain and the manifestation of the disease.
One of the original commercially available tests was PrecivityAD by C2N. This test needs to be ordered by a physician and was designed to predict the likelihood of Alzheimer's Disease (AD) pathology by analyzing a few key factors:
- The ratio of two variants of amyloid beta proteins, specifically amyloid beta 42 and amyloid beta 40
- The ApoE variant of the patient
- The age of the individual
By amalgamating these variables, the test attempts to gauge the probability of a positive PET scan. While it's too early to draw any definitive conclusions, there are two primary reasons why looking at this data could be valuable:
- Comprehensive Risk Assessment: The test results can be used in combination with other factors like family history, genetics, metabolic health, vascular health and cognitive testing to assess the overall risk.
- Monitoring Interventions: The score could be used as a dynamic indicator to monitor the effectiveness of steps taken to mitigate Alzheimer's risk. If the score decreases, it suggests that the ratio of amyloid beta 42 to amyloid beta 40 has changed favorably and thus risk has been reduced.
Since then, C2N launched a second generation version of the tests, PrecivityAD21, which accounts for serum tau concentration for additional accuracy. In August of 2023, Quest launched a direct-to-consumer version of the test that does not require physician ordering. While the test is not quite as accurate as C2N in predicting a positive PET, it comes at a materially lower cost - $400 as of the date of this writing.
Applicability: Who Should Consider blood amyloid tests?
According to medical experts, the test should be reserved for those at high risk of developing Alzheimer's, as its sensitivity and specificity are still not entirely understood. The key term here is "pre-test probability." The higher the pre-test probability, the more reliable the test becomes in predicting a positive or negative outcome.
Final Thoughts
The emergence of amyloid (and tau) blood tests is an exciting development in the field of Alzheimer's research and prevention. Although not a complete solution, they do provide an additional layer of information that can potentially enhance our ability to serve people at risk of developing disease. As our grasp of amyloid biomarkers improves, these tests could become integral parts of a broader, more nuanced approach to diagnosis and risk assessment.
Update April 19, 2024
Roche, in collaboration with Eli Lilly, has launched the Elecsys pTau-2172 blood test, which has recently received breakthrough device designation from the FDA. This means it was recognized as an effective tool for diagnosis, and is a critical milestone in how we identify Alzheimer's Disease. This test targets the tau protein pTau-217 and has the unique ability to distinguish AD from other neurodegenerative diseases. This is particularly important given that clinical AD diagnoses often lack sensitivity and specificity. It’s all the more since over half of patients with cognitive impairment remain undiagnosed or incorrectly diagnosed. This advancement promises to enhance early diagnostic accuracy and significantly improve intervention strategies for AD, particularly as global dementia figures are projected to rise sharply by 2050. pTau-217 is now available as an add-on service with BetterBrain.
Saunas and Alzheimer's: Hot Topic or Just Hot Air?
For centuries, saunas have been lauded for their supposed health benefits, from improved cardiovascular function to detoxification. The recent trends around longevity seem to have revitalized the use of saunas, now considered a popular "health hack". But could spending time in these heated chambers also benefit your brain? Recent research suggests that sauna use might indeed play a role in mitigating the risk of Alzheimer's disease. In this article, we'll explore the scientific evidence behind this claim and consider how sauna use may impact your brain health.
The Connection Between Saunas and Alzheimer's Disease
The Finnish Study
A study from Finland has brought attention to the potential benefits of saunas for brain health. According to the 2,315 person study1, men who used a sauna 4-7 times a week showed a 65% reduced risk of Alzheimer's disease compared to those who used it once a week. Although the study mainly focused on men and thus requires further exploration for generalization, the findings are promising - 65% is a staggering number. If true, this would imply we could cut Alzheimer's prevalence from 6 million to 2 million in the US if only everyone used the sauna daily!
The Underlying Mechanisms
Scientists have proposed several mechanisms through which saunas may benefit the brain. One suggestion is that saunas can significantly improve sleep quality and time in deep sleep, which improves the brain's ability to clear toxic proteins. Moreover, heat stress activates heat shock proteins that can repair damaged proteins, which may play a role in neurodegenerative diseases like Alzheimer's. Lastly, saunas may improve various markers of vascular function, such as blood pressure and blood circulation, known risk factors for Alzheimer's.
Caveats and Considerations
First, the impact was more muted for those who used the sauna only 2-3 times a week (~22% risk reduction). Additionally, while the Finnish study shows a correlation, and certainly attempted to control for relevant variables, it is always very challenging to prove causation in retrospective studies.
Conclusion
The notion that saunas could "incinerate" your Alzheimer's risk is captivating, they should not be viewed as a standalone solution. While promising studies hint at a beneficial correlation, saunas are not a guaranteed prevention method for Alzheimer's. However, given their other health benefits and the intriguing data suggesting a potential role in brain health, saunas could be a worthwhile addition to your wellness routine. Plus, who doesn't enjoy an intense sauna session followed by a cold plunge or shower?