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sulin Signaling ?Oxidative Stress Alzheimer’s Parkinson’s Altered Pathways Environmental Factors Chronic Disease Profound Public Health Impact Of EnvironmentallyDriven Western Disease Cluster ? Obesity/overweight – 2/3 US adults, prevalence x2 in ~25 yrs ? Pre/Diabetes – 40% US adults, prevalence DM ~x2 over 20 yrs Cowie 09, ? Cardiovascular disease – still leading cause of death. Hypertension increasing. Hajjar 03 ? Metabolic syndrome = early signs of other cluster diseases。 84 yrs old, Alzheimer?s Assoc. Alzheimer’s Disease/dementia ? Not an inevitable feature of normal aging. ? Progressive impairment of memory and multiple other cognitive functions, severe enough to interfere with daily functioning. ? Expected to triple by midcentury to over 13 million. ? Likely caused by varying binations of geic and environmental factors. ? Annual costs in US over $150 billion. Parkinson’s Disease ? Progressive movement disorder that includes tremors, stiffness, and slow movement. May lead to severe disability. ? Likely caused by variable binations of geic and environmental factors. ? About 50,000 new cases annually in US.* ? Prevalence in US expected to double by 2030.* * Due to the lack of registries and baseline data on Parkinson?s Disease, the figures used here are estimates. Alzheimer’s and Parkinson’s Diseases ? Characterized by: abnormal protein deposits chronic inflammation abnormal oxidative stress ? Many neuroscientists are beginning to think of some neurodegenerative diseases along a continuum, without clearly distinct boundaries in clinical or pathological manifestations Continuum of AgeAssociated Cognitive Impairment Environment Drives Chronic Disease ? Early life experiences can influence laterlife health and disease. ? Multiple factors interact to influence health amp。 Disease built environment disease stress energy chemicals nutrients An ecological health framework considers the individual in the context of family, munity, society, and ecosystem. Altered Pathways Environment Drives Chronic Disease Environmental Factors Inflammation Disrupted Insulin Signaling Oxidative Stress Chronic Disease Mechanisms of Action Defined by microscopic characteristics amp。 mediators CLASSICAL CONCEPT OF INFLAMMATION Defined by appearance. “Calor, dolor, rubor, tumor.” Heat, pain, redness, swelling. The New Concept of Inflammation “Atherosclerosis is an inflammatory disease.” (2) Ross, Russell. Atherosclerosis – An Inflammatory Disease. NEJM 1999, 340(2)。 Pharmacotherapy 56 (2022) 365379. Years % of calories from fat mg/day High Glycemic Carbohydrates Increase the Risk of Chronic Disease High glycemic carbohydrates break down quickly during digestion, rapidly releasing glucose (sugar) into the bloodstream. Δ Plasma Insulin,mg/dl Time, mins INSULINEMIC RESPONSE Low glycemic food High glycemic food Properties of Fatty Acids Omega3 Omega6 Saturated Food Perishable Durable Increased in System Short shelf life Processed foods factory farmed Increased in Long shelf life animals pasture fed animals Immune Antiinflammatory Inflammatory amp。 total mortality DeLogeril 94 ? 60% ↓ cardiac events in CVD patients* Ornish 98 ? ~50% ↓ metabolic synd