APOE Genetics and Dementia Risk

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Can you predict when “bad things” will happen to your health—and more importantly, can you do anything about it? In this episode, I break down which prediction tools actually help you live long and well (because you can act on them), and which ones are mostly expensive fortune-telling. Joined by cardiologist Dr. Anthony Pearson (author of The Skeptical Cardiologist), we dig into heart-risk calculators, dementia genetics, and why biological age clocks aren’t ready for prime time.

Guest: Dr. Anthony Pearson, cardiologist and writer of The Skeptical Cardiologist (Substack)

Key topics & takeaways

• Why “prediction” only matters if it changes what you do—and improves real outcomes.
• A red flag to watch for: is the person promoting the tool also selling the test, supplements, or “hacks” to fix it?
• A sobering reality check: even doctors’ YouTube claims often lack strong evidence (and the least evidence-based content gets more views).
• Heart disease risk equations: the gold standard in prediction because we can reduce risk factors (BP, LDL/ApoB, smoking, diabetes) and clinical trials show outcomes improve.
• But even good tools miss people: a study of <65-year-olds who had heart attacks found many were labeled “low risk” beforehand.
• Dementia genetics (ApoE): ApoE4 raises risk (especially E4/E4), but it’s not destiny. You can’t change genes—so the value of testing depends on whether it motivates healthy behaviors or creates anxiety.
• Biological age clocks: fascinating research, messy consumer product. Different tests disagree, repeat testing can vary wildly, and most importantly—no proof that “lowering” a clock improves health outcomes or longevity. My advice: save your money (for now).

Links & resources mentioned

• Wall Street Journal: longevity calculators for retirement planning: https://www.wsj.com/personal-finance/retirement/i-tried-answering-a-big-unknown-in-retirement-planning-how-long-will-i-live-9ef468df
  
  
• Evidence behind doctors’ YouTube claims (JAMA Network Open): https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2844038
  
  
• Example of strong claims vs broader evidence debate (Substack): https://substack.com/@drjasonfung1/p-182794806
  
  
• Framingham Heart Study overview (risk factors history): https://pmc.ncbi.nlm.nih.gov/articles/PMC4159698/
  
  
• Heart-attack patients labeled “low risk” by calculators (JACC Advances): https://www.jacc.org/doi/10.1016/j.jacadv.2025.102361
  
  
• Biological age clock reliability issues (comparison across clocks): https://pmc.ncbi.nlm.nih.gov/articles/PMC9586209/
  
  

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