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This episode reframes Alzheimer’s disease by tracing how the plaque-first narrative emerged from rare genetic mutations—and why most age-related cognitive decline is actually driven by systemic metabolic and microvascular health. We break down the evidence across neurodegenerative diseases, highlight what truly predicts risk, and outline four powerful levers that individuals can control today: sleep, lipid management, insulin sensitivity, and exercise.

We begin by mapping the spectrum of Alzheimer’s, Lewy body, Parkinson’s, and vascular dementia, explaining why these conditions often lead to death through complications like aspiration and infection. We clarify the difference between APOE isoforms as probabilistic risk versus deterministic genes such as APP, PSEN1, and PSEN2, which drive rare early-onset disease. We revisit the rise—and unraveling—of the amyloid hypothesis, including failed trials and the controversy that reshaped the field.

Then we turn to what the data supports: cardiology’s APOB as a model biomarker, the role of microvascular injury in the brain, insulin resistance as a driver of neuroinflammation, and the metabolic underpinnings of long-term cognitive decline. We present the four proven pillars of brain protection and outline a practical three-hour weekly plan built around strength training, intervals, and BDNF-boosting movement.

High-volume keywords used: Alzheimer’s prevention, brain health, metabolic health, microvascular disease, insulin resistance, APOE, exercise, dementia risk

Listener Takeaways

• Why most cognitive decline is metabolic and microvascular—not amyloid-first
• The difference between APOE risk and deterministic Alzheimer’s genes
• How sleep, lipids, insulin sensitivity, and exercise protect the brain
• The role of APOB, glymphatic clearance, and insulin resistance in decline
• A practical three-hour weekly training plan to lower lifetime risk

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This podcast is created by Ai for educational and entertainment purposes only and does not constitute professional medical or health advice. Please talk to your healthcare team for medical advice.

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