Lifestyle, Genes, and the Prevention of Alzheimer’s disease Ronald G. Munger, Ph.D., M.P.H.

2. Lifestyle, Genes, and the Prevention of Alzheimer’s disease Ronald G. Munger, Ph.D., M.P.H. Center for Epidemiologic Studies Department of Nutrition and Food Sciences

3. Mark Twain Ralph Waldo Emerson

4. Dr. Alois Alzheimer Frau Auguste D. First case-report

5. Alzheimer’s disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. AD is not a part of normal aging. AD is caused by a fatal disease that affects the brain. U.S. National Institute on Aging

6. Research in Utah can lead to discoveries of the causes of Alzheimer’s disease

7. lzheimer’s research at USU?

9. Cache County Ranked No. 1 in the Nation forFemale Life Expectancy in the 1990Murray, C. et al, Harvard Center for Population Studies, 1998 CACHE * 70.0-77.1 77.1-78.1 78.1-78.6 78.6-79.1 79.1-79.5 79.5-80.1 80.1-80.8 80.8-90.0

11. Epidemic? • “Outbreak” of recognition? • Increase in number susceptible? • Increase in rate of occurrence?

12. Alzheimers disease: • Burden and causes • The Cache County Study on Memory, Health, and Aging • Future challenges and partnerships

13. Projected Prevalence of AD 14.3 15 10 Millions 4.8 5 2.9 0 1980 2000 2050 Estimated Number of Americanswith Alzheimer’s Disease (Evans et al. 1989)

14. Direct and Indirect Costs of AD Annual economic toll in U.S.: $80–$100 billion $ 4.4 billion $ 4.1 billion Source of payment: Federal Government State Governments Patients' Families $ 81.5 billion (source:National Institute on Aging and the Alzheimer’s Association)

15. Business cost for workers who are caregivers: $36.5 B Business cost of health care: $24.6 B Total business cost (2002): $61.1 B

17. Cognitive Function

18. Hippocampus:where short-term memories are converted to long-term memories • Thalamus:receives sensory and limbic information and sends to cerebral cortex • Hypothalamus:monitors certain activities and controls body’s internal clock • Limbic system:controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)

19. Alzheimer’s disease and the Brain Mild to Moderate AD Severe AD Preclinical AD

20. Neurons in the brain must: • Communicate • Carry out metabolism • Repair themselves. • Alzheimer’s disease disrupts all three of these essential functions.

22. Mechanisms of Neuron Cell Death:Amyloid-beta plaquesNeurofibrillary tangles

23. The Cache County Study on Memory, Health, and Aging

24. Objectiveof the Cache County Study: • Better understanding of the roles of environmental and genetic factors in Alzheimer’s disease and other forms of dementia in Cache County, Utah.

25. The Cache County Study on Memory, Health, and Aging • Prospective cohort study of dementia and cognitive decline

26. Longitudinal design of the Cache County Study Clinical examinations and expert consensus conferences to diagnose dementia Diet, lifestyle, and cognitive function assessed before onset of disease Continuing assessments; collection of biological samples Cognitive Function Post-mortem studies Year of study

27. The Cache County Study • 5092 participants in 1995 baseline survey • 90% of all residents aged 65+ years • Age range: 65-105 years • Average age: 75 yrs

29. The Cache County Study Detailed assessment of: • cognitive function • nutritional status • medical history and use of medications • functional status (self-reported) • behavioral and lifestyle characteristics

30. Findingsof the Cache CountyStudy: • 10% of Cache County senior residents suffer from dementia, a rate higher than found in some previous studies.

31. Incidence of AD is Higher in Women than Men after Age 80 Women Discrete annual hazard (adjusted) Men Age

32. Findingsof the Cache CountyStudy on Memory in Aging: • Common medications may reduce the risk of Alzheimer’s disease: • Anti-inflammatory medications • Long-term estrogen use • Supplemental vitamins C and E

33. Supplements or food for a healthy diet?

34. Food sources of nutrients and healthy dietary patterns are more strongly associated with protection of cognitive function than supplement use.

35. Apolipoprotein E (APOE) is involved in lipid metabolism APOE A genetic variant of APOE (e4 allele) increases the risk of Alzheimer’s disease

36. Cache County Study on Memory in Aging Incidence of AD, by age, sex, and no. of APOE 4 alleles • Women • Men 2 4’s 1 4 No 4’s Miech et al., 2002

38. Chronic diseases and AD

39. Baseline characteristics (1995)

40. Diabetes is known to increase the risk of vascular diseases

41. Diabetes in Cache County: • Associated with loss of memory in both men and women • Associated with new cases of Alzheimer’s disease in men • In men: diabetes + APOE-e4 genotype interact to further increase risk of AD

43. Future approaches and innovations • Family-based studies • Brain imaging • Biological markers – “metabolomics” • Statistical methods and Informatics

44. Future approaches • Family-based studies • Gene-discovery • Social, economic, environmental factors • Gene-environment interactions

49. The Utah Population Database: A resource for pedigree and population research Geri Mineau, Ph.D., Director Huntsman Cancer Institute at the University of Utah vvvvvvvvvvvvvvv

50. The Utah Population Database: Records available: Genealogy 1,600,000 Birth 2,100,000 Death 700,000 Cancer 320,000 Driver’s lic. 2,700,000 Total 9,000,000+ vvvvvvvvvvvvvvv