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 appreciated^1,2. 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 dementia^3,4. 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. 

‍

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 decline^2,3. 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.

‍

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.

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 studies^2,3 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.

‍

As the quest for effective Alzheimer’s prevention continues, recent studies^1,2 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 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:

1. 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.
2. 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.