GreyMatters
Educational articles, BetterBrain resources, latest in brain health, and news about us. Written for you, with expertise (and love).
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.
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.
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?
Why Is Alzheimer's More Common in Women?
When it comes to Alzheimer's disease, gender plays an undeniable role. A staggering two-thirds of those diagnosed with Alzheimer's in the United States are women. This disparity has puzzled researchers for years. Initially, many attributed it to the longer lifespan of women compared to men. However, as our understanding of the disease deepens, we've learned that longevity alone doesn't fully explain the 2X difference in prevalence.
The Longevity Theory Falls Short
For a long time, the prevailing explanation for why more women than men were diagnosed with Alzheimer's was simple: women live longer, and Alzheimer's is a disease that primarily affects older adults. However, this explanation has increasingly come under scrutiny. As it turns out, the difference in lifespan between men and women isn't sufficient to account for the wide gap in Alzheimer's cases. The narrative is much more nuanced and involves a complex interplay of biological and social factors.
The Menopause Transition Hypothesis
Menopause is a significant biological milestone in a woman's life, marked by the end of menstrual cycles and fertile years. One of the most significant changes that accompany menopause is a decline in estrogen levels. Estrogen is not just a reproductive hormone; it also has protective effects on the brain. The sharp decrease in estrogen during the menopause transition has been hypothesized to elevate the risk of Alzheimer's among women. In fact, cognitive decline associated with reduced estrogen levels has been reported, especially during the peri-menopausal and post-menopausal phases.
A beacon of hope: Hormone Replacement Therapy (HRT)
Given the hypothesized link between menopause and Alzheimer's risk, Hormone Replacement Therapy (HRT) has been studied as a potential preventive measure. Some evidence indicates that HRT could mitigate the risk of Alzheimer's among post-menopausal women. One prospective study1in particular demonstrated a 41% reduction in the risk of Alzheimer's in women who did HRT vs those who did not. Of course, any decision to start HRT should be made through a physician who can account for all contraindications.
The Often Overlooked Role of Caregiving
The gender disparity in Alzheimer's doesn't end with disease prevalence; it also manifests in caregiving. Women make up a significant majority of Alzheimer's caregivers, often bearing the emotional and physical burden of caring for afflicted family members. This role can lead to heightened stress levels, which in turn could potentially impact a woman’s own cognitive health.
Conclusion
The question of why Alzheimer's disproportionately affects women is far from straightforward. While the longevity theory has been partially debunked, the menopause transition and its hormonal changes offer a compelling avenue for understanding the gender disparity in Alzheimer's prevalence. Even social factors like caregiving roles cannot be discounted. Understanding these contributing factors can pave the way for gender-specific preventive strategies, which are beginning to be implemented in clinical practice.
Should you get tested for APOE4?
Chance are, you know someone who has tested for their APOE genotype. With the advent of consumer genotyping companies such as 23andme, genetic testing for Alzheimer's risk has become increasingly accessible, with the APOE4 gene variant taking center stage in the discussion. The question that many people are asking is: Should I get tested for APOE4? This article aims to provide a balanced perspective, detailing the pros and cons to help you make an informed decision.
What Is APOE4?
The APOE gene produces a protein essential for fat metabolism and is involved in brain cell repair. There are three main variants of this gene—APOE2, APOE3, and APOE4—with the APOE4 variant being strongly associated with an increased risk of developing Alzheimer's disease. While having this gene variant doesn't guarantee that you'll develop Alzheimer's, it can significantly elevate your risk. 20-25% of people have 1 copy of APOE4, conferring a 2-3X increase in Alzheimer's risk, while 2-3% of people have 2 copies, which implies an 8-10X increase in risk.
Advantages of APOE4 Testing
Empowers You to Make Informed Choices
Perhaps the most compelling reason for getting tested is the ability to make informed decisions about your health. There are specific recommendations for those carrying APOE4 such as significantly increasing DHA consumption given impaired absorption. Additionally, research suggests that APOE4 carriers get even more benefit from a range of interventions than non-carriers. In fact, some experts suggest that by applying the right interventions, you can completely mitigate the impact of having a copy of APOE4.
Opens opportunities for clinical trials and futures therapies
There is a significant research focus on APOE4 and potential pharmacological approaches to mitigating the associated risk. Testing may open up avenues for participating in such trials. Furthermore, as therapies get approved in the future for APOE4 carriers, you'll be well positioned to take advantage.
Offers Information for Family Planning
Your genetic makeup doesn't just affect you; it could also be informative for your family members. Given the heritability of the gene, knowing that you carry the APOE4 variant could give valuable insights into your relatives such as parents who may be at higher risk for developing dementia.
Drawbacks of APOE4 Testing
Carries Emotional and Psychological Weight
Although APOE4 is simply a risk factor and is far from being deterministic, finding out that you're at higher risk for Alzheimer's can be emotionally taxing. While the REVEAL study1 showed that disclosing ApoE4 status did not cause clinically significant anxiety or depression after 6 month follow up, responses are of course very individualized. Before taking the test, consider whether you're emotionally prepared for the results.
Doesn't Guarantee Prevention or Cure
At present, there is no cure for Alzheimer's. Knowing you have the APOE4 gene can offer a sense of urgency to adopt preventive measures, but it doesn't guarantee that you'll be able to ward off the disease.
Raises Ethical and Privacy Concerns
Genetic testing often brings up privacy issues. There's always the risk of data leaks or misuse by third parties, including insurance companies, even though laws exist to prevent genetic discrimination (e.g., GINA for health insurance). Be aware of these concerns when contemplating testing.
The Decision is Yours to Make
Choosing whether to undergo APOE4 testing is a deeply personal decision that should be based on multiple factors, including your emotional readiness, family history, and the current state of your cognitive health. Regardless of your decision, remember that the genetics are just one piece of a very complicated puzzle.
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.
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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?
Why Is Alzheimer's More Common in Women?
When it comes to Alzheimer's disease, gender plays an undeniable role. A staggering two-thirds of those diagnosed with Alzheimer's in the United States are women. This disparity has puzzled researchers for years. Initially, many attributed it to the longer lifespan of women compared to men. However, as our understanding of the disease deepens, we've learned that longevity alone doesn't fully explain the 2X difference in prevalence.
The Longevity Theory Falls Short
For a long time, the prevailing explanation for why more women than men were diagnosed with Alzheimer's was simple: women live longer, and Alzheimer's is a disease that primarily affects older adults. However, this explanation has increasingly come under scrutiny. As it turns out, the difference in lifespan between men and women isn't sufficient to account for the wide gap in Alzheimer's cases. The narrative is much more nuanced and involves a complex interplay of biological and social factors.
The Menopause Transition Hypothesis
Menopause is a significant biological milestone in a woman's life, marked by the end of menstrual cycles and fertile years. One of the most significant changes that accompany menopause is a decline in estrogen levels. Estrogen is not just a reproductive hormone; it also has protective effects on the brain. The sharp decrease in estrogen during the menopause transition has been hypothesized to elevate the risk of Alzheimer's among women. In fact, cognitive decline associated with reduced estrogen levels has been reported, especially during the peri-menopausal and post-menopausal phases.
A beacon of hope: Hormone Replacement Therapy (HRT)
Given the hypothesized link between menopause and Alzheimer's risk, Hormone Replacement Therapy (HRT) has been studied as a potential preventive measure. Some evidence indicates that HRT could mitigate the risk of Alzheimer's among post-menopausal women. One prospective study1in particular demonstrated a 41% reduction in the risk of Alzheimer's in women who did HRT vs those who did not. Of course, any decision to start HRT should be made through a physician who can account for all contraindications.
The Often Overlooked Role of Caregiving
The gender disparity in Alzheimer's doesn't end with disease prevalence; it also manifests in caregiving. Women make up a significant majority of Alzheimer's caregivers, often bearing the emotional and physical burden of caring for afflicted family members. This role can lead to heightened stress levels, which in turn could potentially impact a woman’s own cognitive health.
Conclusion
The question of why Alzheimer's disproportionately affects women is far from straightforward. While the longevity theory has been partially debunked, the menopause transition and its hormonal changes offer a compelling avenue for understanding the gender disparity in Alzheimer's prevalence. Even social factors like caregiving roles cannot be discounted. Understanding these contributing factors can pave the way for gender-specific preventive strategies, which are beginning to be implemented in clinical practice.
Should you get tested for APOE4?
Chance are, you know someone who has tested for their APOE genotype. With the advent of consumer genotyping companies such as 23andme, genetic testing for Alzheimer's risk has become increasingly accessible, with the APOE4 gene variant taking center stage in the discussion. The question that many people are asking is: Should I get tested for APOE4? This article aims to provide a balanced perspective, detailing the pros and cons to help you make an informed decision.
What Is APOE4?
The APOE gene produces a protein essential for fat metabolism and is involved in brain cell repair. There are three main variants of this gene—APOE2, APOE3, and APOE4—with the APOE4 variant being strongly associated with an increased risk of developing Alzheimer's disease. While having this gene variant doesn't guarantee that you'll develop Alzheimer's, it can significantly elevate your risk. 20-25% of people have 1 copy of APOE4, conferring a 2-3X increase in Alzheimer's risk, while 2-3% of people have 2 copies, which implies an 8-10X increase in risk.
Advantages of APOE4 Testing
Empowers You to Make Informed Choices
Perhaps the most compelling reason for getting tested is the ability to make informed decisions about your health. There are specific recommendations for those carrying APOE4 such as significantly increasing DHA consumption given impaired absorption. Additionally, research suggests that APOE4 carriers get even more benefit from a range of interventions than non-carriers. In fact, some experts suggest that by applying the right interventions, you can completely mitigate the impact of having a copy of APOE4.
Opens opportunities for clinical trials and futures therapies
There is a significant research focus on APOE4 and potential pharmacological approaches to mitigating the associated risk. Testing may open up avenues for participating in such trials. Furthermore, as therapies get approved in the future for APOE4 carriers, you'll be well positioned to take advantage.
Offers Information for Family Planning
Your genetic makeup doesn't just affect you; it could also be informative for your family members. Given the heritability of the gene, knowing that you carry the APOE4 variant could give valuable insights into your relatives such as parents who may be at higher risk for developing dementia.
Drawbacks of APOE4 Testing
Carries Emotional and Psychological Weight
Although APOE4 is simply a risk factor and is far from being deterministic, finding out that you're at higher risk for Alzheimer's can be emotionally taxing. While the REVEAL study1 showed that disclosing ApoE4 status did not cause clinically significant anxiety or depression after 6 month follow up, responses are of course very individualized. Before taking the test, consider whether you're emotionally prepared for the results.
Doesn't Guarantee Prevention or Cure
At present, there is no cure for Alzheimer's. Knowing you have the APOE4 gene can offer a sense of urgency to adopt preventive measures, but it doesn't guarantee that you'll be able to ward off the disease.
Raises Ethical and Privacy Concerns
Genetic testing often brings up privacy issues. There's always the risk of data leaks or misuse by third parties, including insurance companies, even though laws exist to prevent genetic discrimination (e.g., GINA for health insurance). Be aware of these concerns when contemplating testing.
The Decision is Yours to Make
Choosing whether to undergo APOE4 testing is a deeply personal decision that should be based on multiple factors, including your emotional readiness, family history, and the current state of your cognitive health. Regardless of your decision, remember that the genetics are just one piece of a very complicated puzzle.