GreyMatters
Educational articles, BetterBrain resources, latest in brain health, and news about us. Written for you, with expertise (and love).
The Glymphatic System: Why Deep Sleep Is Your Brain's Best Cleanup Tool
What if the most important thing you could do for your brain tonight was also the most straightforward? Not a new supplement or a complicated protocol. Just better sleep, specifically the deep stages most people shortchange without knowing it.
Here is the biology that makes that matter more than most people appreciate.
Your brain has its own plumbing. It only fully runs at night.
Every other tissue in your body has a lymphatic system to carry away metabolic waste. For a long time, the brain was thought to be the exception, with no obvious mechanism for the job. That changed in 2013 when researchers described the glymphatic system: a network that uses cerebrospinal fluid to flush waste out of brain tissue, including amyloid-beta and tau, the proteins that accumulate in Alzheimer's disease.
The connection to sleep came alongside it. Glymphatic clearance is not constant. It ramps up dramatically during deep, slow-wave sleep, when the spaces between brain cells expand and fluid can move through more freely. This is one of the clearest biological explanations for why sleep is not optional maintenance. It is when a specific, measurable cleanup process actually runs, protecting your brain now and building resilience for decades to come.
What the newer research tells us about the engine
The system's existence has been well established for over a decade. What researchers kept working on was the mechanics: what physically moves the fluid?
A 2025 study published in Cell from Maiken Nedergaard's lab (one of the teams behind the original glymphatic work) helps answer that. In mice, the team found that during deep sleep a small brainstem region called the locus coeruleus releases norepinephrine in slow, rhythmic waves, roughly one every fifty seconds. Each wave gently tightens and relaxes the blood vessels, and that slow oscillation appears to drive cerebrospinal fluid through the brain, moving waste along.
The result connects three things already known to be related (deep sleep, blood-vessel tone, and fluid clearance) into a single mechanism. Deep sleep is not the brain idling. It is the brain running a coordinated pump.
Two points of context worth holding on to. First, this is animal research. The mechanism has been demonstrated in mice, whose sleep biology is a strong but imperfect model for humans. It tells us how the system likely works, not the conclusion of a human clinical trial.
Second, the same study found that zolpidem (the active ingredient in Ambien) suppressed these norepinephrine waves in mice and reduced fluid flow. That is a genuinely interesting signal, but it is a finding in animals about a mechanism, not evidence that a prescription harms people. If you take a sleep aid, this is not a reason to stop. It is a reason to make sleep quality a real conversation with your prescriber.
What this means in practice
None of this requires a new gadget. It gives you a sharper reason to take the fundamentals seriously.
Protect the deep-sleep window. Slow-wave sleep is concentrated in the first half of the night. A consistent wake time, morning light exposure within thirty minutes of getting up, and a cool, dark room are the most reliable ways to support it. These are habits that compound over years.
Be honest about alcohol and late meals. Both fragment the deep-sleep stages where clearance is most active. You may fall asleep quickly and still miss the part of the night that matters most for this system.
Treat sleep as something measurable. The same way we use biomarkers to track what is working, sleep consistency and quality are worth paying attention to over time rather than estimating from how you feel in the morning.
Take loud snoring or daytime exhaustion seriously. Both can signal sleep apnea, which repeatedly disrupts the deep sleep this system depends on. It is common, often undiagnosed, and very treatable.
If you use a sleep medication, bring the goal of better sleep quality to your prescriber rather than changing anything on your own.
BetterBrain's brain health coaches work with clients to turn sleep from a vague intention into a specific, trackable practice built around your schedule, your biology, and your data. Think sharper now, and protect your brain for decades.
Tommy Wood's 3-S Model: The Science Behind Future-Proofing Your Brain
The Framework Behind What We Do at BetterBrain
Our Chief Science Officer Tommy Wood published The Stimulated Mind in March 2026, and we think it's the most complete, accessible guide to dementia prevention that exists right now. A rigorous, science-backed model for understanding what your brain actually needs across a lifetime, written by someone who has spent his career studying exactly this.
At the center of the book is what Tommy calls the 3-S Model: Stimulation, Support (sleep and recovery), and Supply (of energy and nutrients). These aren't three separate suggestions. They're three categories of input the brain depends on, and Tommy's argument is that they reinforce each other in ways most people don't appreciate. They synergize, providing outsized benefits from even simple changes across all three.
BetterBrain is built around exactly this model. The 10 health systems and 11 practices our coaches work through with you are the operational version of what Tommy lays out in the book. Here's a breakdown of each S and one thing you can act on this week.
S1: Stimulation
The first S is the one that surprises people. Tommy's argument is that the brain, like muscle, needs ongoing challenges to maintain its structure. The variable that matters is novelty. Doing the same crossword every day is not stimulation in the sense your brain cares about. Learning a language, picking up a new instrument, or taking a class on something you have no prior context for, are stimulating.
This connects to what researchers call cognitive reserve: the buffer your brain builds through years of varied learning. Cognitive reserve is one of the strongest predictors of who maintains function in their 70s and 80s, even in the presence of pathology like amyloid plaques.
What you can do this week: Pick one thing this month that you don't already know how to do. It doesn't have to be heavy, a new recipe technique, a new fitness class, a new route on your morning walk that requires you to navigate. The brain treats novelty as a signal that it needs to keep adapting.
S2: Support (Sleep and Recovery)
The second S is the one most people know is important and still underestimate. Recovery, especially during sleep, is when the brain adapts and improves.
While you sleep, your brain runs a waste-clearance system that flushes out the proteins that build up during the day, including amyloid, the same protein that accumulates in Alzheimer's disease. Think of it like a dishwasher that only runs at night. Skip enough nights, or get consistently shallow sleep, and the dishes pile up. Disrupted sleep is associated with elevated pTau-217, lower cognitive scores, and higher long-term dementia risk.
Tommy is direct about this in the book: there is no supplement protocol that compensates for chronically poor sleep. And the work has to start with the structure of your sleep itself, meaning how much time you actually spend in the deep and REM stages, not just how many hours you're in bed. You can sleep eight hours and still miss most of the stages where the real restoration happens.
What you can do this week: Protect a consistent wake time. The wake time matters more than the bedtime because it anchors your body's internal clock. Pair it with morning light within 30 minutes of getting up, and you've done more for your sleep quality than most people manage with supplements or sleep trackers alone.
S3: Supply (Energy and Nutrients)
The third S is where a meaningful part of your biomarker picture lives. Your brain runs on a continuous supply of glucose, oxygen, omega-3 fatty acids, B vitamins, and a long list of micronutrients. Deficits in any of these can quietly compromise function for years before they show up as symptoms. When these markers are at optimal levels, they actively protect your brain, often for decades.
The first place to look is diet. What you eat every day is the primary driver of whether your brain gets what it needs. Targeted supplementation comes second, once you know where the gaps actually are.
The biomarkers we look at first in the Blueprint panel are homocysteine, vitamin D, vitamin B12, ferritin, and folate. These are the ones most likely to flag a nutrient supply problem before you feel it. And the fix is usually targeted, not maximal. Most clients don't need fifteen supplements, they need the right two or three, chosen based on what their labs actually show.
What you can do this week: If you haven't had a full brain-health panel in the past year, that's where to start. A nutrient gap rarely shows up in isolation, and the right intervention depends on seeing how everything fits together.
Why All Three Matter Together
The argument the book makes is that the components that support brain health aren't a long list of individual variables, they're an integrated network.
Stimulation without sleep doesn't give the brain time to consolidate. Sleep without nutrient supply leaves the brain trying to do its overnight work without raw materials. Nutrient supply without stimulation gives the brain everything it needs to grow but no reason to.
This is consistent with what BetterBrain's coaches see in practice. Clients who work hard on one of the three but ignore the others tend to plateau. The ones who address all three see the biggest shifts in biomarkers, cognitive scores, and how they actually feel.
The Bottom Line
The Stimulated Mind is the best communication of modern brain science available today, worth reading whether you're at the beginning of thinking about brain health or several years into a protocol.
Working with a BetterBrain coach to address all three Ss, across all 11 practices, is how you turn a framework into measurable results.
hs-CRP: The Biomarker Most Likely to Flag Silent Inflammation in Brain Health
If you have ever had a routine blood panel, you have probably seen "CRP" on the list. What you may not have seen is "hs-CRP," which sounds like the same test but is not. The difference matters a lot for brain health.
This piece walks through what hs-CRP measures, why it shows up in almost every BetterBrain protocol, and what to do if yours is elevated.
What hs-CRP measures
C-reactive protein is made by your liver in response to inflammation anywhere in your body. The "hs" stands for "high-sensitivity," which means the test can detect very low levels of CRP that the standard CRP test cannot.
This distinction sounds technical but it is the whole reason we use hs-CRP and not standard CRP. Standard CRP is designed to spot acute inflammation, like an active infection or a recent injury. The values it flags are high enough to indicate something is actively wrong right now. hs-CRP is designed to spot chronic low-grade inflammation, the kind that does not feel like anything but is associated with long-term risk for cardiovascular disease, type 2 diabetes, and cognitive decline.
For brain health, the chronic low-grade version is the one that matters.
Why this matters for your brain
Chronic systemic inflammation is associated with neuroinflammation, the inflammatory state of the brain itself. The mechanism is not fully understood, but the body of evidence is large. People with higher long-term hs-CRP have higher rates of cognitive decline, faster brain atrophy on imaging, and elevated risk of Alzheimer's disease.
Inflammation does not directly cause Alzheimer's. But it appears to be one of the upstream conditions that lets the underlying pathology progress more quickly. Lowering it is one of the few interventions where the evidence is consistent across cardiovascular, metabolic, and cognitive outcomes.
What the numbers mean
- Optimal: under 1.0 mg/L
- Borderline: 1.0 to 3.0 mg/L
- High: above 3.0 mg/L
Most standard labs flag a result only when it crosses 3.0 mg/L or higher. The 1.0 to 3.0 range is where a meaningful number of clients are quietly running elevated. Their primary care has waved it off as "in range." For brain health purposes, it is not.
The biomarkers that pair with hs-CRP
A single hs-CRP value is informative but more useful in context. The markers to look at alongside it:
Homocysteine. Elevated homocysteine is associated with both inflammation and methylation problems. If hs-CRP and homocysteine are both elevated, the inflammation is likely driven in part by nutrient gaps.
ApoB and Lp(a). Cardiovascular markers. Elevated hs-CRP plus elevated ApoB is a particularly bad combination for vascular brain health.
HbA1c and Fasting Insulin. Metabolic markers. Glycemic dysfunction drives systemic inflammation. If hs-CRP is elevated, look here next.
Ferritin. Iron storage. Elevated ferritin can indicate underlying inflammation, separate from iron status.
The picture you assemble from these markers tells you whether the inflammation is metabolic, vascular, nutrient-driven, or something else.
What to do about it
The interventions that consistently move hs-CRP overlap with the interventions that consistently move long-term cognitive trajectory. Sleep, glycemic control, omega-3 status, dental health, gut health, and visceral fat reduction are all associated with lower chronic inflammation over time. None of them are quick fixes. All of them compound.
For BetterBrain clients with elevated hs-CRP, the coaching protocol usually starts with the highest-leverage area their panel reveals. A client whose hs-CRP is elevated alongside high HbA1c starts with glycemic control. A client whose hs-CRP is elevated alongside high homocysteine starts with methylated B-complex and a closer look at folate, B12, and B6 intake. The technique is to follow the panel.
Find out where you stand
hs-CRP is one of the most useful brain-health markers in routine bloodwork, and one of the most commonly missed. If you have not had a high-sensitivity version of CRP measured in the past year, it is worth checking.
BetterBrain Blueprint covers hs-CRP alongside 50+ other markers and starts at $89 with insurance.
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The Essential Techniques our coaches keep recommending for brain health
We use the term Essential Techniques inside BetterBrain a lot. Each BetterBrain Practice (Move, Sleep, Eat, De-Stress, and so on) is made up of specific techniques, and the Essential Techniques are the ones our panel of clinical advisors identified as the techniques with the greatest evidence and broadest applicability.
These are not techniques for a specific kind of client. They are the techniques worth considering for almost everyone thinking about long-term brain health, regardless of starting point, age, or risk profile. About 15 to 20 percent of the techniques in our library are Essential. The other 80 to 85 percent are context-dependent, applied when a client's panel or situation calls for them. A coach builds a personalized action plan by looking across the whole library, deciding which Essentials to elevate first and which context-dependent techniques to layer in. The Essentials are the foundation underneath every plan.
We asked some of our coaches what trends they are seeing across the clients they work with, and which Essential Techniques those trends keep pointing back to.
The post-meal walk (Move Practice)
Maggie works with clients across the metabolic-health side of our client base. The trend she keeps seeing: HbA1c and fasting insulin numbers creeping into pre-diabetic ranges, often without the client realizing it. Many of them are exercising, but most of them are not walking after meals.
"Ten minutes after each meal. That is the rule I get the highest compliance on, because nobody can argue they don't have ten minutes. And it does more than people expect."
This is one of the Essential Techniques in our Move Practice because the evidence is broad and the bar to entry is low. A short walk after eating blunts the post-meal glucose spike. Repeated over months, it is one of the most reliable ways we have seen to shift HbA1c, fasting insulin, and the metabolic conditions that drive midlife brain atrophy. The cost is nothing, the schedule disruption is minimal, and the long-term payoff compounds. It is essential because it works for almost everyone.
Consistent wake time and morning light (Sleep Practice)
Emily works with a large share of our clients who came to BetterBrain because of family history of dementia. The trend she keeps seeing: anxious clients arriving with long supplement lists, wanting to talk about pTau-217 and APOE4, while sleeping six or fewer hours a night.
"One night of four hours isn't really the question. The question is why someone is typically sleeping four or five hours at most. Patterns matter. What we identify from the first visit and where we end up is more than one night of poor sleep. Sleep is the foundation. Exercise goals, stress management, eating, they all land once sleep patterns are optimized."
The Essential Technique Emily points to first is in our Sleep Practice: a consistent wake time paired with morning light. The reason this is essential for almost everyone is the glymphatic system. Sleep is the period during which the brain runs its only clearance system, including the clearance of amyloid. A consistent wake time anchors the circadian rhythm, and morning light reinforces it. The evidence is strong, the intervention is free, and it works for clients in their 30s and their 70s.
Strength training (Move Practice)
Wendy works with many of our clients in their late fifties and sixties. The trend she keeps seeing: clients who are doing aerobic exercise faithfully, often three or four days a week, and skipping strength training entirely.
"I'm flexible with many aspects of a health plan, but strength training is one area I strongly encourage people not to overlook. The research connecting muscle mass and brain health after 50 is incredibly compelling, and maintaining strength now can have a major impact on long-term health and quality of life."
Strength training is another Essential Technique in our Move Practice. The reason it is essential, not optional: muscle is the primary site of glucose disposal in the body, the pathways linked to neurogenesis are responsive to resistance training, and sarcopenia is one of the strongest predictors of cognitive decline in older adults. The evidence supports two sessions a week, moderate intensity, sustained for at least six months. Bodyweight work and resistance bands are enough to start. The technique is essential because everyone past 30 is slowly losing muscle, and the cost of skipping it is too high.
Methylated B-complex (Supplement Practice)
Another trend we keep seeing across our client base: people arriving with homocysteine in the 11 to 14 range, told by their primary care that it is fine. The gap between what is flagged at most labs and what is optimal for brain health is one of the cleanest examples of where our framework differs from standard care.
The optimal range for homocysteine is under 9 μmol/L. Most labs flag a result only above 15. The 9 to 14 range is where a meaningful number of clients are quietly carrying elevated risk that has been waved off. A methylated B-complex moves the marker for the majority of clients within three months, and the cognitive payoff is real.
The Essential Technique in our Eat Practice is targeted methylated B-complex supplementation. The reason this is essential for almost everyone has to do with the underlying biology. Homocysteine is cleared through methylation pathways that depend on the active forms of folate, B12, and B6. A significant portion of the population carries variants of the MTHFR gene that reduce how well the body converts standard folic acid into the active form. Methylated B-complexes deliver the active forms directly. For anyone over 40 thinking about long-term brain health, this is one of the highest-leverage interventions available.
What the pattern reveals
Across our coaches with different specialties and different client populations, the same Essential Techniques keep coming up. These are the techniques that consistently move the needle, regardless of who is doing them. What our coaches actually do day to day is build action plans that span the full technique library, prioritizing among the Essentials and layering in the context-dependent techniques that fit each client's panel and life.
The Essentials are universal. The action plan is personal.
Find out where to start
If you'd like a quick read on which Essential Techniques to prioritize based on what you are already doing, take the free Essential Scan. Open to anyone, whether you're already a BetterBrain client or just starting.
If you'd like a deeper personalized action plan, BetterBrain coaching pairs you with a Brain Health Coach who builds the plan with you. Coaching is covered at $0 for 92% of approved clients with qualifying insurance.
Visceral Fat and the Brain: What 16 Years of Data Actually Show
A study just landed in Nature Communications that reframes how to think about midlife weight loss and brain health. Researchers followed 533 adults for up to 16 years after they completed lifestyle interventions, then scanned their brains and tested their cognition. The finding: it wasn't weight loss that predicted slower brain atrophy and better cognitive scores years later. It was sustained loss of visceral fat specifically.
This matters because most people, and most doctors, still track weight on a scale. The number on the scale lumps together fat, muscle, water, and where on the body the fat actually sits. The new data suggests that for brain health, where the fat is matters more than how much of it there is.
What the study found
The research, called the Follow-Interventions-Trials (FIT) project, pulled participants from four earlier 18 to 24 month lifestyle randomized trials. The average age at follow-up was 61. Each participant had abdominal MRI, brain MRI, and Montreal Cognitive Assessment (MoCA) testing 5 to 16 years after their original intervention.
Three findings stood out. Lower long-term visceral fat exposure, calculated across baseline, post-intervention, and follow-up, independently predicted higher cognitive scores. Visceral fat loss during the intervention period predicted higher brain volumes years later, independent of overall weight loss. And among the participants who had three full sets of scans over the years, lower long-term visceral fat was associated with a slower rate of brain atrophy.
The same patterns were not observed for subcutaneous fat, the kind that sits under the skin and shows up on a pinch test. Visceral fat, the deeper fat surrounding the organs, was the variable that mattered.
The proposed mechanism is glycemic. Visceral fat is metabolically active. It secretes inflammatory signals and contributes to insulin resistance. Both of these are increasingly understood as drivers of cognitive decline. When visceral fat goes down, glycemic control improves, and the brain appears to benefit downstream.
Why this changes how we think about midlife weight
Most people who decide to lose weight in their fifties do not distinguish between subcutaneous fat, visceral fat, and muscle. Many lose all three. Losing muscle in midlife is a problem on its own. Losing subcutaneous fat without losing visceral fat is largely cosmetic. Losing visceral fat appears to be the part that actually protects the brain.
This also reframes "skinny fat." A person can have a body mass index in the normal range and still carry significant visceral fat. The scale will not flag this. A waist measurement, a DEXA scan, or abdominal imaging will.
For anyone in their 40s, 50s, or 60s thinking about brain health, the practical question is no longer "should I lose weight." It is "what is my visceral fat doing, and what is actually moving it."
What you can do
Three things tend to move visceral fat without requiring dramatic restriction.
The first is reducing refined carbohydrates and added sugars. Visceral fat is more responsive to insulin signaling than subcutaneous fat. Lowering postprandial glucose spikes is associated with reduced visceral fat over time.
The second is consistent moderate-intensity movement, especially after meals. A 10 to 15 minute walk after eating blunts the post-meal glucose curve. Repeated over months, this contributes meaningfully to visceral fat reduction.
The third is strength training, which we covered last week. Muscle is the primary site of glucose disposal in the body. More muscle means better glycemic control, which means less visceral fat accumulation.
The biomarkers that respond, and the ones we look at first with members, are HbA1c (your average blood sugar over three months), fasting insulin, and the broader metabolic panel that looks at lipids and liver function. These shift before the scale shifts. They tell you whether the metabolic conditions that drive visceral fat are improving.
The bottom line
The next time someone tells you to lose weight for your brain, the more useful version of that advice is to lose visceral fat for your brain. The number on the scale was always a poor proxy for what is happening inside the body. The new research makes that clearer.
If you are already a BetterBrain member, your most recent HbA1c, fasting insulin, and metabolic panel results are in your dashboard. Worth a fresh look in light of this.
If you have not yet started, these markers are part of the BetterBrain Essentials Panel we look at first.
Strength Training and Brain Health: What 6 Months of Lifting Does to Your Hippocampus
Strength Training and Brain Health: What 6 Months of Lifting Does to Your Hippocampus
Aerobic exercise gets most of the brain-health attention. The cardiovascular benefits are well-documented, the GPLD1 pathway connecting movement to blood-brain barrier repair is real, and almost every brain health protocol recommends it.
But a body of research has been quietly building on a different type of exercise entirely. And a comprehensive 2025 network meta-analysis just made the case for strength training impossible to ignore.
What the research found
The analysis, published in Frontiers in Aging Neuroscience, pulled data from dozens of randomized controlled trials involving cognitively healthy older adults. When researchers compared aerobic exercise, resistance training, mind-body practices like yoga, and combined programs for their effect on cognitive function, resistance training produced the strongest overall effect on global cognition. The effect size was considered moderate to large in cognitive research, where meaningful improvements are notoriously difficult to achieve.
A parallel 2025 systematic review went further. It examined actual brain imaging alongside cognitive testing. The findings: at least two resistance training sessions per week, sustained for at least six months, were associated with measurable increases in cortical thickness in two critical brain regions.
The hippocampus, your brain's primary memory formation center. And the prefrontal cortex, involved in planning, complex reasoning, and self-control. These are precisely the regions most vulnerable to aging and most associated with early cognitive decline.
These weren't just improvements in test scores. These were structural changes in brain tissue, visible on MRI scans. Six months of consistent strength training literally changed the physical structure of participants' brains.
How it works
The mechanisms connecting resistance training to brain health are distinct from aerobic exercise benefits, which is exactly why both matter.
When your skeletal muscles contract under load, they secrete signaling proteins called myokines into your bloodstream. One well-studied myokine, irisin, crosses the blood-brain barrier and has been shown to increase new brain cell formation and reduce neuroinflammation in research models.
Resistance training also improves insulin sensitivity in your muscles, contributing to better metabolic health throughout your body. Given that brain insulin resistance is increasingly understood as a central mechanism in Alzheimer's disease, this metabolic pathway from strength training to brain protection isn't minor.
The exact dose the research supports
Frequency: At least two sessions per week. Some studies suggest three sessions produce greater effects, following a dose-response pattern.
Duration: Six months minimum for structural brain changes to appear on imaging. This isn't a quick fix. It's a sustained practice.
Intensity: Moderate intensity works best, approximately 50 to 70 percent of your maximum. In practical terms, this means lifting a weight you can complete 8 to 12 controlled repetitions with, where the final 2 to 3 reps require genuine effort.
Going through the motions with very light resistance doesn't appear to produce the same stimulus. The dose matters as much as the activity itself.
You don't need a gym membership to start. Bodyweight exercises (squats, push-ups, lunges), resistance bands, or even filled water bottles work. The goal is progressive challenge over time, gradually increasing difficulty as you get stronger.
Tracking whether it's working
Several markers respond to consistent strength training and give you objective evidence the work is paying off.
Insulin sensitivity: Resistance training improves how your cells respond to insulin. You can track this through fasting insulin and HbA1c, which shows your average blood sugar control over three months. Better insulin sensitivity is associated with better cognitive function.
Inflammatory markers: Consistent strength training reduces systemic inflammation. hs-CRP and homocysteine levels respond, giving objective evidence of the anti-inflammatory effect.
Metabolic health markers: Strength training improves multiple metabolic markers including glucose control, lipid profiles like VLDL-C, and overall metabolic function. These improvements happen through muscle-mediated pathways that complement what aerobic exercise does.
Seeing these numbers move is concrete evidence that the effort is producing real change.
The case for combining aerobic and resistance training
Aerobic exercise works through the GPLD1 pathway, where your liver releases protective signals during movement that repair your blood-brain barrier.
Strength training works through entirely different pathways: muscle-derived signaling proteins, improved insulin sensitivity, and hormonal changes that protect brain structure.
These are complementary, not redundant. Research on combined programs shows that doing both produces greater cognitive benefit than either alone. If you're already doing aerobic exercise regularly, adding just two strength sessions per week hits the research-backed minimum.
If you're curious where your insulin sensitivity, inflammation, and metabolic markers stand, BetterBrain's Blueprint testing covers all of them in a single panel, plus 40 more brain health markers.
Get immediate insights with a 3 minute assessment
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GreyMatters
Cholesterol and Your Brain: What You Actually Need to Know
Cholesterol gets a bad rap. For decades, we've heard that it clogs arteries and causes heart attacks. But here's what doesn't make headlines: your brain contains 25% of your body's total cholesterol despite making up only 2% of your body weight. As lipid expert Dr. Tom Dayspring puts it, "Cholesterol is almost certainly the most important molecule in the brain."
So how can cholesterol be both necessary for brain function and a major cardiovascular risk factor? The answer lies in understanding where cholesterol is, how it gets there, and what form it takes.
In this post, we're taking a deeper dive into cholesterol than usual. We'll break down what your cholesterol numbers actually mean, why the standard tests miss critical information, and how the cholesterol story connects cardiovascular health to brain health.
The Basics: What Is Cholesterol?
Cholesterol is a fatty molecule that serves critical functions throughout your body. It forms the outer layer of every cell, helps produce hormones (including testosterone, estrogen, and cortisol), enables vitamin D synthesis, and supports nerve function. Without cholesterol, you simply couldn't survive.
But there's an important distinction to make: "cholesterol" isn't one thing.
When we talk about cholesterol in the blood versus cholesterol in the brain, we're really talking about two separate systems that operate differently.
Blood cholesterol: Cholesterol travels through your bloodstream inside particles called lipoproteins. These particles come in different types:
- LDL (low-density lipoprotein): Often called "bad" cholesterol, LDL particles deliver cholesterol to cells throughout your body
- HDL (high-density lipoprotein): Called "good" cholesterol, HDL particles help transport excess cholesterol back to the liver
- VLDL (very low-density lipoprotein): Primarily transports triglycerides but also carries some cholesterol
- IDL (intermediate-density lipoprotein): A transition form between VLDL and LDL
Brain cholesterol: Your brain makes its own cholesterol and keeps it completely separate from blood cholesterol. The blood-brain barrier prevents cholesterol in your bloodstream from entering your brain. This means the cholesterol circulating in your blood and the cholesterol in your brain are part of two entirely different pools.
The Heart Risk: Why apoB Matters More Than LDL?
What is apoB?
ApoB (apolipoprotein B) is a protein found on the surface of all atherogenic (plaque-forming) particles, including LDL, VLDL, IDL, and Lp(a). Each particle contains exactly one apoB molecule, making apoB a direct count of total potentially harmful particles.
Why apoB beats LDL cholesterol?
Traditional LDL-C (LDL cholesterol) tells you how much cholesterol LDL carries, but not how many particles you have. Two people can have identical LDL-C but vastly different particle numbers and risk levels.
- Many small LDL particles (each carrying less cholesterol) = "normal" LDL-C but high particle count and high risk
- Fewer large LDL particles (each carrying more cholesterol) = higher LDL-C but fewer particles and potentially lower risk
ApoB counts every atherogenic particle regardless of size. This makes it the best single marker for cardiovascular risk.
What is the triglyceride connection?
Elevated triglycerides (often from insulin resistance) fundamentally alter lipid metabolism:
- VLDL becomes triglyceride-enriched
- Particles get remodeled into small, dense LDL
- ApoB particle count increases
- You can have "normal" LDL-C but dangerously high apoB
This is why metabolic health is critical for cardiovascular risk.
The Brain Side: Why Cholesterol Is Essential
While high apoB threatens your heart, brain cholesterol is absolutely essential.
Critical brain functions
- Myelin formation: Insulates nerve fibers for rapid signal transmission
- Synapse formation: Creates and maintains neuron connections
- Cell membranes: Every neuron needs cholesterol-rich membranes
- Neurotransmitter release: Regulates how neurons communicate
How the brain gets cholesterol
Astrocytes (brain cells) produce cholesterol and package it into brain-specific lipoproteins containing apoE (apolipoprotein E) for delivery to neurons.
The APOE genetic factor
- APOE ε2: Protective against Alzheimer's, better cholesterol handling
- APOE ε3: Most common, considered neutral
- APOE ε4: Increases Alzheimer's risk, disrupts brain cholesterol metabolism
Research from MIT shows APOE4 is associated with brain cells accumulating cholesterol abnormally rather than using it to make healthy myelin. This isn't about too much or too little cholesterol, but how effectively the brain uses it.
Cholesterol and Alzheimer's
Brain regions vulnerable to Alzheimer's show signatures of being "super cholesterol-hungry," as researchers describe it, constantly trying to produce and absorb cholesterol. When this system fails (especially with APOE4), neurodegeneration may follow.
The Paradox Resolved
In the bloodstream: High apoB drives atherosclerosis. Particles penetrate artery walls, oxidize, trigger inflammation, form plaques. Goal: Keep apoB low (<60-80 mg/dL) to prevent cardiovascular disease.
In the brain: The brain makes its own cholesterol independently. Blood cholesterol can't cross the blood-brain barrier. Goal: Support healthy brain cholesterol metabolism through metabolic health.
This separation means lowering blood cholesterol doesn't starve your brain. Your brain continues making what it needs regardless of apoB levels.
The Bottom Line
Cholesterol isn't inherently good or bad; context is everything. In your bloodstream, high apoB poses serious cardiovascular and cerebrovascular risks. In your brain, cholesterol is essential for structure and function.
The good news: these systems are separate. Lowering apoB to protect your heart doesn't harm your brain. In fact, protecting your cardiovascular system through better lipid management, metabolic health, and inflammation control also protects your brain.
Understanding which biomarkers matter empowers informed decisions. It's not about fearing cholesterol; it's about managing it intelligently.
Want to Understand Your Complete Lipid Profile and Genetic Risk?
BetterBrain includes apoB, advanced lipid testing, metabolic biomarkers, and APOE genetic testing for a complete cardiovascular and brain health picture.
Dietary Defenders: Prebiotic Fibers in Alzheimer's Prevention
As Alzheimer's disease continues to impact millions globally, the scientific community is increasingly focusing on the gut-brain axis. This complex communication network, which links the gastrointestinal tract and the brain, could play a major role in preventing cognitive decline. Recent discoveries1 have shown that gut microbiota might affect everything from brain development to behavior to disease states, and researchers are starting to explore how the gut-brain axis can influence dementia risk.
Exploratory study: A closer look at fiber's impact on aging brains
The School of Life Course & Population Sciences at King’s College London spearheaded a pivotal double-blind study2 (the same type of study as used for clinical trials) with participants over 60 years old. Their research aimed to uncover the cognitive effects of consuming prebiotic fibers compared to a placebo.
Fiber fuels cognitive fortitude
Like any organism, the components making up the gut microbiome need food to survive. One source of nutrients for them is prebiotic fibers, such as inulin and fructooligosaccharides (FOS), both of which were the focus of the King’s College study. The researchers found that participants who took prebiotic supplements had more of one species of healthy bacteria called Bifidobacterium in their gut. This species has previously been linked to better cognitive performance, and indeed the participants who took supplements showed improved cognitive function scores through the same memory tests that are used as an early indicator of Alzheimer’s disease.
Why is this happening?
The composition of the gut microbiome has drastically changed over human history. Advances in agriculture, industrialization and globalization may have caused a decrease in gut microbial diversity, which has been associated with worse health outcomes. In particular, a review of multiple studies1 suggests that changes in the microbiome can lead to behavioral changes. In another study3 comparing 25 patients diagnosed with Alheimer’s disease to 25 healthy individuals, those with Alzheimer’s were found to have reduced gut microbial diversity.
Keeping an eye on your intake
Let’s get specific. Women should aim to consume 21-25g of fiber per day. Men should aim for 30-38g4. Here is a list of some common fiber-dense foods to consider adding into your diet.
A promising path to cognitive health
Emerging evidence connecting dietary habits, gut microbiota, and brain function highlights a novel approach to combat Alzheimer’s disease. The gut-brain axis is still a new area of research - there is much we don’t know, and many researchers around the world are investigating the different ways in which the microbiome influences our brain health. Such studies not only pave the way for innovative therapeutic avenues but also emphasize the profound impact our diet can have on mental and overall health.
Putting the science in action
- Eat enough fiber each day to make sure you are nourishing your gut microbiome. Women should strive for 21-25g daily, while men should aim for 30-38g.
- Learn more about the importance of your gut health on your brain and body through the Peter Attia Drive podcast.some text
- Episode #215 goes in-depth on the GI system - skip to 34:30 for ways in which the gut and brain communicate, and to 1:55:00 for ways to promote your gut microbiome using your nutrition.
- Episode #283 discusses the microbiome specifically - learn more about the importance of fiber at 38:30 and about the gut-brain axis at 50:15.
The Role of Homocysteine in Dementia Risk
Homocysteine is a naturally occurring amino acid in our body and can spike acutely, such as after staying up all night. In healthy people, homocysteine naturally clears over time. However, at chronic high concentrations, it is associated with various health issues, including heart disease and, notably, cognitive decline. In fact, having blood homocysteine levels over 14 μmol/L is associated with a nearly doubled risk of dementia1. Luckily, there are simple ways to lower your homocysteine levels - most notably B vitamin supplementation.
Brain Atrophy, Aging and Cognitive Decline
As we age, our brains naturally undergo some amount of atrophy, or decrease in size, which involves a loss of neurons and their connections. This process is accelerated in Alzheimer’s dementia2. With a lower brain volume and fewer neural connections, it’s easy to see how atrophy can lead to lasting cognitive impairment. One factor that has a strong influence on the rate of brain atrophy is blood concentration of homocysteine. Several studies3,4 link elevated homocysteine levels are linked with a heightened risk of dementia.
The role of B vitamins
You won’t often hear us say this, but you have an ace up your sleeve in fighting homocysteine: B vitamins. One study2 investigated the effects of using B6, B9, and B12 vitamins over the course of two years, using the same level of rigor that is commonly used for drug clinical trials.
On average, people who used B vitamins lowered their overall homocysteine levels by 32% and experienced a 30% slower rate of brain atrophy. In fact, those who started with very high levels of blood homocysteine (> 14 μmol/L) managed to slow their atrophy rate by 53%. In other words, this study suggests that the simple act of taking a daily B vitamin supplement can cut your dementia risk in half.
The type of B vitamin matters
There are two factors to consider when selecting a B vitamin supplement. The first is what vitamins you are getting. The study mentioned above specifically tested the use of vitamins B6, B9 (also known as folate), and B12. It’s important to get a mix of both. The second is whether or not you select the methylated form of the vitamins. Methylation is a biological process that makes the vitamins more available for your body to use. In other words, the same dose of methyl-B vitamins will be more strongly absorbed than normal B vitamins. This is especially important for people with mutations in the MTHFR gene, since they otherwise have trouble absorbing B vitamins. We generally recommend taking methylated B vitamins since they are perfectly safe, but if you are sensitive to overmethylation, you may want to consider regular B vitamins to avoid side effects like headaches, anxiety, or irritability.
Broader Implications for Dementia Prevention
Homocysteine is a critically important risk factor for dementia. Not only does it accelerate brain atrophy, it also aggravates other conditions through inflammation and oxidative stress. Thankfully, B vitamins are an extremely effective tool to lower homocysteine levels. While there are many other ways of managing your homocysteine levels, most notably through diet, exercise, and stress management, B vitamins are a low-effort high-impact way to keep your brain atrophy at bay.
Get started on managing your homocysteine
- Measure your blood homocysteine levels to learn where you stand. Homocysteine is one of the 50+ biomarkers tested during your BetterBrain Essentials blood draw.
- Consider using B vitamin supplements to lower your homocysteine, ideally below 9 μmol/L. We recommend Pure Encapsulations MethylAssist, but make sure you use an unmethylated alternative if you are sensitive to overmethylation.
- Learn more about homocysteine on the Peter Attia Drive episode on dementia. This episode covers many topics, so if you’re just interested in homocystine, skip ahead to 1:09:00.
Clearing the Air: How Pollution Influences Alzheimer's Risk
When you think of air pollution, respiratory disease is usually the first thing to come to mind. However, recent findings from the Emory Healthy Brain Study1 has begun to show that long-term exposure to tiny particles called PM2.5 has been associated with the accumulation of amyloid plaques in the brain, which is a hallmark of Alzheimer's disease. While this doesn't prove that PM2.5 exposure leads to Alzheimer's, it suggests a potentially elevated risk, especially among those exposed to poor quality air over longer periods of time.
Air quality is typically measured by the amount of specific pollutants in the air. The Emory Healthy Brain Study looked at a type of pollutant called PM2.5, which is fine particulate matter with a diameter of less than 2.5 micrometers (about 30 times smaller than a human hair). These particles are so fine they can bypass the body's airway defenses and enter the bloodstream. Common sources of PM2.5 include vehicle emissions, industrial combustion, and natural occurrences like wildfires. Because the particles can enter the bloodstream, they can cause health issues that go beyond simple respiratory irritation, potentially affecting brain health and contributing to cognitive decline.
Key Findings from the Study
- Increased PM2.5 exposure is associated with worse results on Alzheimer’s pathology biomarkers: The study indicated that higher levels of PM2.5 exposure over one and three years are associated with lower concentrations of amyloid-beta 42 (Aβ42) in cerebrospinal fluid (CSF). Aβ42 is a biomarker whose decreased levels suggest an accumulation of amyloid plaques in the brain, which is a hallmark of Alzheimer’s dementia.
- Specific Focus on Traffic-Related PM2.5: While the study looked at both ambient (general environmental) and traffic-related PM2.5, the findings were particularly noteworthy for ambient PM2.5. This suggests that while traffic contributes significantly to PM2.5 levels, other sources of pollution also play a crucial role in influencing Alzheimer’s disease biomarkers.
- Implications for Alzheimer’s Risk: The research underscores that even PM2.5 below levels currently considered risky by environmental standards, there is a tangible increase in the risk of developing Alzheimer’s disease. This calls for a reassessment of what is considered “safe” exposure to PM2.5, particularly for populations at risk of Alzheimer’s.
Reducing Exposure
Individuals living in high pollution areas can reduce their exposure by:
- Using air purifiers at home
- Avoiding outdoor activities when pollution levels are high
- Supporting clean air initiatives aimed at reducing emissions
Conclusion
The findings from Emory University’s research are a vital addition to our understanding of environmental factors in Alzheimer’s disease risk. They not only highlight the need for stricter air pollution controls but also suggest that everyday actions to reduce exposure to PM2.5 could be a feasible strategy for Alzheimer's prevention. As we continue to uncover more about the impact of our environment on health, it becomes increasingly clear that tackling air pollution is not just about preserving our planet—it's also about protecting our minds.
Fighting Dementia with CBT: A proactive approach
Cognitive-behavioral therapy (CBT) has long been recognized as a powerful tool in managing mental health disorders, but its potential role in preventing dementia is only beginning to be appreciated1,2. There are two ways that CBT can help. First, CBT is a powerful tool which can combat anxiety, depression, and other mental health disorders, which increase the risk of dementia3,4. Second, CBT can be used to facilitate habit change - that is to say, help users adopt behaviors which promote brain health.
How does CBT work?
CBT is a structured form of psychotherapy that relies on the principle of identifying and changing certain thought patterns and behaviors. The underlying principle is that the brain is “plastic” or flexible throughout life, which means that we can shape the connections our brain makes. The therapy is collaborative, with the client and therapist working together to set goals and practice new skills. The specifics of a CBT session will vary depending on the needs of each individual, but sessions generally involve recognizing distorted thinking, challenging irrational beliefs, and developing healthier responses. CBT also encourages behavioral changes by gradually facing fears or engaging in positive activities.
CBT in Alzheimer’s prevention
Combating mental illness
Your mental health is closely linked to your brain health. Depression, anxiety, and other disorders can actually increase inflammatory stress in your brain and disrupt your cognitive function. There are several different approaches to treating mental illness, and CBT happens to be highly effective for some people.
Forming healthy habits
Much of dementia prevention relies on addressing known lifestyle risk factors, things like physical inactivity, poor diet, diabetes, and high blood pressure. Forming and maintaining healthy habits can feel challenging, but CBT can help facilitate behavior change and keep you on the right track.
Common CBT principles
Because CBT is a tool, many of its principles apply just as well to managing mental health as to improving lifestyle habits. Common techniques include:
- Awareness and Identification: CBT begins with helping individuals become more aware of their current state. What situations or thoughts trigger a negative cascade? Which of my habits aren’t the healthiest?
- Cognitive Restructuring: This is a fancy way of saying challenging negative thoughts. By examining negative emotions and thoughts, individuals can start to think about them objectively. For mental health, this can be changing “something catastrophic will happen” to “I can take on this challenge.” For habit formation, this may be replacing "changing my diet won’t make a difference" with "every healthy meal contributes to my resilience."
- Behavioral Experiments: CBT employs behavioral experiments to challenge negative beliefs and test out new behaviors in a controlled manner. This may look like gradually facing a feared situation, engaging in activities that carry a sense of accomplishment, or starting to exercise with 10-minute daily walks. The purpose here is to gain confidence and reinforce the challenge to negative thoughts with real-life actions.
- Goal Setting: Together with a therapist, individuals set specific, achievable goals related to their needs. These may be thing like developing problem-solving skills to improve their sense of control, or things like increasing weekly physical exertion. The most important thing is for these goals to feel realistic and manageable.
- Reinforcement: Positive changes are reinforced through self-monitoring and resilience techniques. Tracking change over time helps establish a feedback loop where improvement becomes a natural motivator, while practical skills for managing setbacks help sustain long-term behavior change.
By systematically working through these steps, CBT provides individuals with the tools and confidence to implement and sustain changes - many of which contribute to preventing dementia.
A strong tool for prevention
It’s important to recognize that CBT isn’t a silver bullet - it’s a tool that’s helped millions of people, and it requires conscious work to implement. With that said, the potential of CBT in preventing Alzheimer’s is vast. It not only helps address mental illness, but also incorporates lifestyle changes that tackle the physiological underpinnings of dementia. Implementing CBT strategies that promote healthy aging could be key in reducing the burden of dementia, emphasizing prevention over treatment and maintaining cognitive vitality well into the later years of life.
Resources on finding CBT providers
If you are interested in trying CBT, there’s several ways to get started.
- Online directories and telehealth platforms can help you find a professional to work with. You can often find therapists through your insurance plan or your employee benefits, or through listing websites like Zocdoc or Psychology Today. You can also look on telehealth platforms like Talkspace or Betterhelp, though not all of these accept insurance.
- Community health centers often also provide CBT services. These are typically available at reduced rates, and focus primarily on mental health.
- Books can help you learn more about CBT and its practice. Feeling Great: The revolutionary new treatment for depression and anxiety is a widely praised book by Dr. David Burns, a psychiatrist and professor of Psychiatry at Stanford.
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.