Predicting Alzheimers & Dementia (and minimizing risk)

Fluctuating Cholesterol Tied to Higher Dementia Risk

Unexplained lipid changes in older adults may foretell cognitive decline, study suggests

Year-to-year fluctuations in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were tied to higher risks of cognitive decline and dementia, a study of nearly 10,000 older adults showed.

Participants with the highest variability in total cholesterol had a 60% higher risk of incident dementia (HR 1.60, 95% CI 1.23-2.08) and a 23% higher risk of cognitive decline without dementia (HR 1.23, 95% CI 1.08-1.41), reported Zhen Zhou, PhD, of Monash University in Melbourne, Australia, and co-authors in Neurologyopens in a new tab or window.

https://www.medpagetoday.com/neurology/dementia/114002

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I think the study has implications for the validity of the oft-made assertion that ‘mental exercise’ into old age will stave off cognitive decline.

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No the study is about early life education (did you go to high school, undergrad, master, PhD, etc.) It is unrelated to late life cognitive exercise.


Open Access Paper:

Bioaccumulation of microplastics in decedent human brains

Rising global concentrations of environmental microplastics and nanoplastics (MNPs) drive concerns for human exposure and health outcomes. Complementary methods for the robust detection of tissue MNPs, including pyrolysis gas chromatography–mass spectrometry, attenuated total reflectance–Fourier transform infrared spectroscopy and electron microscopy with energy-dispersive spectroscopy, confirm the presence of MNPs in human kidney, liver and brain. MNPs in these organs primarily consist of polyethylene, with lesser but significant concentrations of other polymers. Brain tissues harbor higher proportions of polyethylene compared to the composition of the plastics in liver or kidney, and electron microscopy verified the nature of the isolated brain MNPs, which present largely as nanoscale shard-like fragments. Plastic concentrations in these decedent tissues were not influenced by age, sex, race/ethnicity or cause of death; the time of death (2016 versus 2024) was a significant factor, with increasing MNP concentrations over time in both liver and brain samples (P = 0.01). Finally, even greater accumulation of MNPs was observed in a cohort of decedent brains with documented dementia diagnosis, with notable deposition in cerebrovascular walls and immune cells. These results highlight a critical need to better understand the routes of exposure, uptake and clearance pathways and potential health consequences of plastics in human tissues, particularly in the brain.

https://www.nature.com/articles/s41591-024-03453-1

Eric Topol’s Analysis:

This issue of Ground Truths sums ups a worrisome new report on brain accumulation of microplastics, increasing over time assessed, with much higher levels in people with dementia, including Alzheimer’s disease. It comes on top of a new study in the experimental model showing microplastics impair brain blood vessel flow and induce blood clots. While these reports do not establish cause-and-effect, they add to a growing body of deeply concerning evidence on the toxic effects of these pervasive substances for our health.

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Given how ubiquitous and unavoidable these microplastic particles are, if they have seriously deleterious health effects, then we are facing a slow moving but massive world wide catastrophy. Present day old people may be the last relatively healthy generation for who knows how long. Anyone 40 and under is up the creek if this transpires to be a serious threat.

I guess it was inevitable, that as humans radically change the natural environment and introduce countless novel and untested molecules into the biosphere, that some of them will turn out to be mortal threats to life on this planet. Maybe cockroaches will survive, and if not, then microbes and viruses, lol.

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Protection from hot work?

Scientists told Whitney that the high levels of heat shock proteins in his brain might be the result of his life experience.

“I spent 20 years in the Navy, most of it in the hot spots, like the engine rooms of ships—110 degrees is nothing on a ship,” he says.

That environment may have caused an increase in heat shock proteins, which were able to limit the spread of tau and prevent the onset of Alzheimer’s.

The scientists studying Whitney aren’t sure if that’s all, or even part, of the explanation. But they are hoping that the paper on Whitney will encourage other researchers to look for answers.

Journal reference:

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Everyone knows we need sufficient magnesium but this paper suggests a fairly large daily dose (greater than 438 mg a day) is brain protective and can reduce the risk of progressing from normal aging to Alzheimer’s, especially for women.

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Keep in mind that SGLT2i are magnesium sparing, so if you take one of those regularly, you don’t need a very high supplement dosage to have plenty of magnesium in the body.

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Deborah,
You might want to look into this:
https://raypeatforum.com/community/threads/increasing-metabolism-may-reverse-alzheimer-disease-ad-and-general-aging.32446/

Also:
https://raypeatforum.com/community/threads/metabolic-dysfunction-is-a-primary-cause-of-aging-and-its-symptom-alzheimer-disease-ad.32454/

And since dementia in its many forms is tied to high blood sugar (the cells are unable to take in and use glucose in the blood), anything that helps the cells take in glucose again is helpful. So, see this:
“aspirin makes cells sensitive to insulin again”
https://lowtoxinforum.com/threads/the-fatty-acid-syndrome-randle-cycle.8157/

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A cocktail for Alzheimer’s

The researchers used APP/PS1 mice, which are genetically modified to express human amyloid-β (Aβ). These mice develop signs of Alzheimer’s disease as the Aβ accumulates, and their cognitive abilities decrease earlier than those of wild-type mice.

In this experiment, 6- to 8-week-old APP/PS1 mice received a human-origin probiotic cocktail for 16 weeks. This treatment led to decreased Aβ accumulation in the hippocampal region of the brain, which is the first region where Alzheimer’s disease changes manifest, and mitigated the mice’s cognitive decline compared to untreated controls, suggesting that the treatment protected against the progression of Alzheimer’s disease.

Reduced inflammation

Apart from Aβ plaques, Alzheimer’s disease is also linked to neuroinflammation. Studies even suggest that systemic inflammation in mid-life can promote cognitive decline even 20 years later [5].

After giving their probiotic cocktail to mice, the researchers observed reduced neuroinflammation, decreased activation of the brain’s immune cells (microglia), and improved integrity of the blood-brain barrier, which regulates the entry of molecules and substances from blood to the brain. Systemic and gut inflammation were also reduced compared to controls, as measured by inflammatory markers in the blood and gut.

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Certain bacteria found in people’s mouths may be linked to changes in brain function as you age, experts have said.

The study, led by the University of Exeter, found certain types of bacteria were associated with better memory and attention, while others were linked to poor brain health and Alzheimer’s disease.

Lead author Dr Joanna L’Heureux said: “We might be able to predict if you have the Alzheimer’s gene even before you start getting problems or think about going to the doctor for a diagnosis.”

The research is in early stages but study leads say they are now investigating whether eating certain healthy foods, such as nitrate-rich leafy greens, can influence brain health by boosting certain bacteria.

https://scitechdaily.com/scientists-discover-mouth-bacteria-linked-to-increased-alzheimers-risk/

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Open Access Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2308719

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https://www.alzforum.org/news/research-news/plasma-p-tau217-flags-alzheimers-pathology-other-disorders

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I now believe that amyloid is just one risk factor amongst many for Alzheimer’s. It is like having high cholesterol, which won’t tell you whether or not you have heart disease but rather only whether you have a risk factor for heart disease. There are people with high cholesterol that never develop heart disease and people with heart disease without high cholesterol. This is because heart disease is multi-factorial and other risk factors, like high blood pressure, also contribute. I believe that we should be viewing amyloid and Alzheimer’s the same way that we view cholesterol and heart disease.

If amyloid is a risk factor that starts to build up decades before Alzheimer’s starts, then maybe we should be removing it preventatively like we control high cholesterol with Statins before it can cause heart disease. Researchers at WashU have started recruiting for a clinical trial aimed at doing just that. People as young as in their twenties, with rare forms of familial Alzheimer’s, are being recruited to take one of Eli Lilly’s anti-amyloid antibody therapeutics for two years a decade or more before they would be expected to develop Alzheimer’s.

Full article:

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people with heart disease without high cholesterol

Is that an accurate statement? I don’t believe so. I guess it depends on your definition of “high cholesterol.” Personally I’d define anyone with LDL/ApoB >= 50 as high because as far as we know it’s possible to develop heart disease at those levels, and the likelihood approaches zero as we go below them. Doubly so for Lp(a) positive people. While this may seem aggressive even for folks on this forum, the reality is even “low” cholesterol (eg 60 ApoB) exposes you to risk that, quite frankly, you don’t need to expose yourself to given the advances in lipid lowering therapy. There are very few people who can’t get below 50 with available therapies side effect free.

OTOH, there really are people with minimal amyloid and tau that have Alzheimer’s disease. Feels like a bit of a flawed comparison.

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ChatGPT seems to think so :wink:

What factors would lead to a person developing heart disease even if they don’t have high cholesterol

ChatGPT said:

There are several factors that can contribute to heart disease even in people without high cholesterol. Some of the most common include:

1. High Blood Pressure (Hypertension)

  • Increases strain on the heart and arteries, leading to damage over time.
  • Can cause the heart to work harder, leading to thickening or stiffening of the heart muscle.

2. Diabetes

  • High blood sugar levels damage blood vessels and nerves that control the heart.
  • Increases inflammation and the likelihood of developing atherosclerosis (narrowed arteries).

3. Smoking

  • Damages blood vessels and reduces oxygen levels in the blood.
  • Increases the risk of blood clots, leading to heart attacks or strokes.

4. Chronic Inflammation

  • Conditions like autoimmune diseases (e.g., lupus, rheumatoid arthritis) can cause chronic inflammation, damaging blood vessels.
  • Even low-grade chronic inflammation (from stress, poor diet, or infections) can contribute to heart disease.

5. Sedentary Lifestyle

  • Lack of physical activity weakens the heart and contributes to poor circulation, high blood pressure, and insulin resistance.

6. Obesity

  • Can lead to metabolic syndrome, which increases the risk of heart disease even if cholesterol levels are normal.
  • Often linked to hypertension, diabetes, and inflammation.

7. Genetics & Family History

  • Some people inherit a predisposition to heart disease, even if their cholesterol is normal.
  • Conditions like hypertrophic cardiomyopathy (HCM) or arrhythmias can lead to heart issues independent of cholesterol levels.

8. Stress & Mental Health

  • Chronic stress increases cortisol and inflammation, which can negatively impact heart health.
  • Depression and anxiety are linked to higher risks of cardiovascular disease.

9. Sleep Disorders (e.g., Sleep Apnea)

  • Poor sleep quality and conditions like obstructive sleep apnea can increase blood pressure and strain the heart.

10. Poor Diet (Even Without High Cholesterol)

  • High sugar intake can contribute to insulin resistance, inflammation, and weight gain.
  • Excessive processed foods and unhealthy fats can harm blood vessels.
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If you say high cholesterol to ChatGPT it’s going to use what’s most encountered in its dataset (weighted probably for quality sources), which will be the standard threshold in medical documents where atheroschlerosis still occur. dicarlo2 said that it depends on definition of high. Ask it instead if there are any people with heart disease where LDL isn’t above 0 (e.g if any cases with total abetalipoproteinemia), or pick 20 & lifelong.

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When I made the post I was thinking of atherosclerosis, the primary cause of heart disease. It is in fact true to say that people can have heart disease without high cholesterol (by any definition of high). Here’s a more precise question and answer by o3-mini

Can you have heart disease without hardened or soft plaques?

Heart disease is an umbrella term that encompasses a wide range of conditions affecting the heart. While atherosclerosis—characterized by the buildup of hardened (calcified) or soft (unstable) plaques in the coronary arteries—is a common cause of coronary artery disease (CAD), it is not the only pathway to heart disease. There are several conditions in which heart disease occurs without the presence of these traditional plaques.

Alternative Mechanisms of Heart Disease

  1. Coronary Microvascular Dysfunction (CMD):

In CMD, the small coronary arterioles fail to dilate properly, leading to inadequate blood flow to the myocardium despite the absence of significant plaque in the larger coronary arteries. Patients can experience angina and ischemic symptoms, but standard imaging tests for larger vessel disease might appear normal.

  1. Coronary Vasospasm:

Transient constriction of the coronary arteries can reduce blood flow. This condition, sometimes referred to as variant or Prinzmetal’s angina, is due to a spasm of the arterial wall rather than a fixed plaque. The temporary nature of the spasm can still lead to myocardial ischemia.

  1. Myocardial Bridging:

This congenital anomaly occurs when a segment of a coronary artery tunnels through the heart muscle rather than lying on its surface. During systole, the tunneled segment can be compressed, which may impair blood flow without the involvement of atherosclerotic plaque.

  1. Inflammatory and Immune-Mediated Cardiomyopathies:

Conditions such as myocarditis, which is inflammation of the heart muscle often triggered by infections or autoimmune processes, can lead to heart disease independently of atherosclerotic plaque formation. Similarly, stress-induced cardiomyopathy (Takotsubo syndrome) involves transient dysfunction of the heart muscle due to emotional or physical stress, without the presence of coronary plaques.

  1. Genetic and Structural Disorders:

Hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy are examples of conditions that primarily involve the heart muscle or electrical system. These diseases may not be associated with coronary plaques but still result in significant cardiac morbidity and mortality.

Clinical Implications

Understanding that heart disease can occur without the classic signs of atherosclerosis is crucial for accurate diagnosis and treatment. Patients presenting with chest pain or other cardiac symptoms may undergo a range of diagnostic tests—from coronary angiography and cardiac MRI to stress tests—that help to differentiate between these conditions. Management strategies will vary considerably depending on the underlying cause; for example, treatments for coronary vasospasm differ from those aimed at atherosclerotic blockages.

Conclusion

Yes, it is entirely possible to have heart disease without the presence of hardened or soft plaques. A variety of mechanisms—including microvascular dysfunction, vasospasm, inflammatory processes, and genetic cardiomyopathies—can lead to heart disease independent of traditional atherosclerosis. Recognizing these differences is key to developing appropriate treatment strategies tailored to the specific underlying pathology.

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Most people use ASCAD and heart disease interchangeably, I don’t think it matters that much.

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This will force evolutionary changes, homo sapiens that are most susceptible to nano/micro plastics where it affects their fertility and/or fetal viability will be diluted out the gene pool. Evolution due to sudden environmental changes is brutal.

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