Month 9 — Brain Health, Dementia Prevention & the Muscle-Brain Axis

1. The 2024 Lancet Commission concluded that up to 45% of dementia cases could theoretically be prevented or delayed. What does that number actually represent?

2. How has the Commission's risk-factor list evolved across its 2017, 2020, and 2024 reports?

3. Which two factors carry the single largest population attributable fractions (7% each) in the 2024 model?

4. Why does the evidence behind high LDL cholesterol differ in quality from the evidence behind untreated vision loss?

5. Which life stage does the Commission identify as carrying the densest cluster of modifiable risk?

6. What is the unifying biology behind LDL, hypertension, diabetes, obesity, smoking, and inactivity as dementia risk factors?

7. Sleep and dietary pattern are not named factors in the Commission's model. What is the most accurate interpretation?

8. The 2015 FINGER trial randomized 1,260 at-risk older adults for two years. What did it actually demonstrate?

9. US POINTER (JAMA 2025) randomized 2,111 adults to a structured versus a self-guided multidomain program. How should the result be read?

10. What is the World-Wide FINGERS network, and why does it matter?

11. The ACHIEVE trial tested hearing intervention over three years and the overall result was null. What was the important subgroup finding?

12. The WHIMS trial tested hormone therapy started in later life for cognitive protection. What happened?

13. What makes microglia biologically distinctive among immune cells?

14. Live imaging overturned the older textbook picture of 'resting' microglia. What did it show?

15. Which set correctly names the four coordinated jobs microglia perform?

16. What does it mean when microglia are described as 'primed'?

17. How should a coach interpret the popular M1 (bad) versus M2 (good) microglia framework?

18. What is the correct reasoning structure when microglial biology meets a client recommendation?

19. In the one-year Erickson trial of previously sedentary adults aged 55–80, aerobic walking increased anterior hippocampal volume by about 2% while the stretching control lost volume. What is the honest read?

20. What are the WHO physical activity targets used as the floor in this module?

21. Why is sleep framed as the nightly window for brain repair, and what is the evidence caveat?

22. Which definition of inflammaging is most accurate?

23. What did Nation (2019) and Montagne (2020) establish about the blood-brain barrier?

24. In Darweesh's prospective meta-analysis, higher CRP (HR 1.37) and higher IL-6 (HR 1.40) were associated with which outcome?

25. Skeletal muscle is described as an endocrine organ. What is the signaling sequence, and what is the key caveat?

26. A client reads that IL-6 causes dementia and also that exercise-induced IL-6 is anti-inflammatory. How do you resolve this?

27. Across BDNF, irisin, cathepsin B, and IGF-1, what is the single most important shared conclusion?

28. Lactate is described as a putative myokine. What evidence tier does the muscle-to-brain lactate story sit at?

29. What does the strongest human outcome data actually show about exercise and the aging brain?

30. Khalafi's meta-analysis found exercise lowered CRP most (SMD −0.45), then TNF-α (−0.30) and IL-6 (−0.17), with larger effects in people who started with chronic disease. In lean, low-inflammation adults the effects were small or null. What is the correct interpretation?

31. Myth or fact: 'Brain aging is a slow subtraction of neurons that we can only slow down and mourn.'

32. A supplement is marketed as 'calming your microglia and switching them to the good state.' What is the accurate response?

33. Myth or fact: 'Because estrogen supports the brain, hormone therapy is a reasonable strategy to prevent cognitive decline in a 68-year-old.'

34. Myth or fact: 'Since ACHIEVE was null overall, treating hearing loss is not worth prioritizing.'

35. A 54-year-old woman in perimenopause has LDL 145 mg/dL, blood pressure 138/86, a sedentary job, mild untreated high-frequency hearing loss, and a family history of dementia. She asks about a nootropic stack. Where should the plan start?

36. A 67-year-old man with type 2 diabetes and central adiposity starts combined aerobic and resistance training. Six months later CRP fell from 4.2 to 2.1 mg/L. His lean, athletic friend does the same program and his CRP does not move. How do you explain this?

37. A client returns from a hard interval session on Tuesday and has fasting labs drawn Wednesday morning. IL-6 and CRP are elevated versus her prior panel. What is the appropriate response?

38. A member asks: 'If I do everything on the Lancet list perfectly, am I 45% safe from dementia?' What is the most accurate and useful answer?

39. Which set best represents the module's 'foundation before frontier' protocol for lifelong brain health?

40. Which item belongs in the 'not yet shown' tier rather than 'well-established'?