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, PrecivityAD2, 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.

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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.

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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.

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.

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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?