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.

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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.

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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. 

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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

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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.

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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.

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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. 

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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 studies^3,4 link elevated homocysteine levels are linked with a heightened risk of dementia. 

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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.

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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. 

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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. 

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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.

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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.

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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.

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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.  

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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. 

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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.

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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.

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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.

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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.

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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.

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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.

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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. 

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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.

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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. 

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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. 

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.

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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. 

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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.

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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:

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• 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)

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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.

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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.

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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.

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.

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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.

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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.

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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. 

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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.

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