3 Jae Hee Kang Palo Alto 2007 speaker notes

Does Diet Play a Role in Dementia Prevention?Data From the Nurses’ Health Study: 

Does Diet Play a Role in Dementia Prevention? Data From the Nurses’ Health Study Jae Hee Kang, ScD Instructor in Medicine Channing Laboratory Department of Medicine Brigham and Women’s Hospital, Boston MA May 21, 2007

Objectives: 

Objectives Cognitive function cohort studies: Purpose: to determine relations between key epidemiologic risk factors and cognitive aging Particular interest: to identify risk factors for earliest stages of cognitive decline Why nutrition is a good target: It can be changed It is under control of the individual

Objectives: 

Objectives Four topic areas: Fruits, vegetables, and antioxidants Fat consumption Insulin and diets that promote insulin resistance Moderate alcohol intake

Impact of onset delay on US AD population projections: 

Impact of onset delay on US AD population projections Intervention (1998) delay of 6 months delay of 1 year delay of 2 years delay of 5 years Effect (by 2007) 100,000 210,000 570,000 1.15 million Brookmeyer et al, Am J Pub Health, 1998

Slide5: 

FRUIT, VEGETABLE AND ANTIOXIDANT INTAKE

Antioxidants: Background: 

Antioxidants: Background Oxidants Products of normal aerobic metabolism and the inflammatory response Oxidative damage in Alzheimer’s disease One of the earliest pathophysiologic events

How might antioxidants prevent Alzheimer’s?: 

How might antioxidants prevent Alzheimer’s? Reduce free radicals that harm brain cells Decrease the toxicity of the amyloid protein Lower cardiovascular disease risk

Where do we find antioxidants?: 

Where do we find antioxidants? Beta Carotene: in foods that are orange in color (carrots, cantaloupe, squash, pumpkin) and some green leafy vegetables Lutein: in green leafy vegetables (spinach, collard greens, kale) Lycopene: in tomatoes, watermelon, papaya, apricots, and pink grapefruit Selenium: in rice, wheat and brazil nuts Vitamin C: in fruits and vegetables Vitamin E: in almonds, wheat germ, safflower, corn, and soybean oils, nuts, and broccoli

Antioxidants: Epidemiological studies: 

Antioxidants: Epidemiological studies Several studies have shown that higher intake of antioxidants, is associated with a lower risk of cognitive decline and Alzheimer disease

Fruits and vegetables and cognitive function in NHS: 

Fruits and vegetables and cognitive function in NHS Nurses’ Health Study (NHS): prospective cohort of 121,700 RNs, began in 1976; followed biennially Cognitive study: ~ 20,000 NHS participants free of stroke and aged 70-81 years at baseline (1995+) Kang et al, 2005 Ann Neurology

NHS: Telephone Cognitive Assessment: 

NHS: Telephone Cognitive Assessment Brief telephone interview cognitive tests: Telephone Interview of Cognitive Status – TICS Verbal Memory: immediate and  delayed recall of TICS 10-word list, East Boston Memory Test-  immed. and  delayed Category Fluency:  Animal naming test Working Memory:  Digit span backwards Global score of all of the above tests Participation rate: 93% follow-up

NHS: Measurement of Fruit & Vegetable Intake and Cognitive Function: 

NHS: Measurement of Fruit & Vegetable Intake and Cognitive Function Start ‘80 ‘84 ‘86 ‘90 ‘94 ‘98 ‘03 of NHS Dietary Assessment using Food Frequency Questionnaires 1st cognitive assessment 2nd cognitive assessment

Slide13: 

FFQ: food frequency questionnaire Validation: 4 1-week weighed diet records vs. FFQ correlation (r) was 0.9 Long-term average intake: Fruits + vegetables: Median 5.6 servings/day Green leafy vegetables: Median 0.8 servings/day Cruciferous vegetables: Median 0.4 servings/day NHS: Measurement of Fruit & Vegetable Intake

NHS: Results: 

NHS: Results No association with all fruits Modest inverse associations between high intake of total vegetables and specific types of vegetables and cognitive decline Green Leafy Vegetables: consumption at highest vs. lowest quintile was cognitively equivalent to being 1.7 years younger Cruciferous Vegetables: consumption at highest vs. lowest quintile was cognitively equivalent to being 1.3 years younger

Chicago Health and Aging Project confirms finding with vegetables: 

Chicago Health and Aging Project confirms finding with vegetables Morris et al 2006 Neurology

ANTIOXIDANTS: ROTTERDAM STUDY: 

ANTIOXIDANTS: ROTTERDAM STUDY TERTILE OF VITAMIN E INTAKE Engelhart et al., JAMA, 2000 RATE RATIO OF ALZHEIMER’S DISEASE

ANTIOXIDANTS: ROTTERDAM STUDY: 

ANTIOXIDANTS: ROTTERDAM STUDY TERTILE OF VITAMIN C INTAKE RATE RATIO OF ALZHEIMER’S DISEASE Engelhart et al., JAMA, 2000

Slide18: 

Grodstein et al, Am J Clin Nutr, 2003 TICS 10-word immed 10-word delayed EBMT immed EBMT delayed * * Fluency Digit span Global score NHS: Vitamin E and C users, compared with non-users * *

Slide19: 

Petersen et al, N Engl J Med, 2005

Summary: Fruits, Vegetables and Antioxidants: 

Limitation of studies Duration of follow-up Later food frequency questionnaires with possible cognitive dysfunction (responses require sustained motivation, attention and memory) Unmeasured confounders Antioxidant intake from food vs. supplement sources – why different results? Summary: Fruits, Vegetables and Antioxidants

INSULIN AND PROMOTERS OF INSULIN RESISTANCE: 

INSULIN AND PROMOTERS OF INSULIN RESISTANCE

Insulin and cognitive function: 

Epidemiologic evidence links diabetes to dementia Elevated insulin secretion and insulin resistance may also be risk factors for cognitive decline Factors that promote insulin resistance and elevated blood insulin levels: Obesity, especially “spare tire” distribution Dietary: high glycemic index pattern and excess intake of sugary foods Insulin and cognitive function

Insulin secretion and cognitive function in NHS: 

Insulin secretion and cognitive function in NHS Study population: Women who had blood drawn between 1989-1990 and had plasma c-peptide measured C-peptide is an excellent measure of insulin secretion Exclusions: anyone with diabetes Total of 718 women Average age at blood draw: 64 years Average interval between blood draw and cognitive testing: 10 years

Mean Differences in Cognitive Function, by C-peptide Quartile: 

Mean Differences in Cognitive Function, by C-peptide Quartile Q1 Q2 Q3 Q4 0 -0.5 -1.0 -1.5 VERBAL MEMORY GLOBAL SCORE Q1 Q2 Q3 Q4 0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 Okereke et al., Arch Intern Med, 2005

Relative Risk of Poor Cognitive Performance, by C-peptide Quartile: 

Relative Risk of Poor Cognitive Performance, by C-peptide Quartile QUARTILE OF PLASMA C-PEPTIDE * * * Okereke et al., Arch Intern Med, 2005

Slide26: 

FAT INTAKE

Fat: mechanisms: 

Fat: mechanisms Different fats may raise or reduce risk of cardiovascular disease – for example, by impact on balance of good/bad cholesterol Possible interactions with APOE gene status High intake of saturated fats may promote insulin resistance and high insulin concentrations High intake of some fats may induce oxidative stress – implicated in Alzheimer and coronary artery diseases

Slide28: 

Columbia Aging Project Luchsinger et al.,Arch Neurol,2002

Slide29: 

Chicago Health and Aging Project Morris et al., Arch Neurol, 2003

Consumption of Fish and Omega-3 Fatty Acids:: 

Consumption of Fish and Omega-3 Fatty Acids: Chicago Health and Aging Project: 815 people, aged 65-94 years Highest intake of fish (once or more weekly) vs. rare/never: RR=0.4 (CI 0.2-0.9) Highest intake of omega-3 fatty acids vs. lowest: RR=0.4 (CI 0.1-0.9) Morris et al, Arch Neurol 2003

Slide31: 

Fat Intake: Rotterdam Study Engelhart et al., Neurology, 2002

Nurses’ Health Study: bad fats are associated with worse performance among diabetics (n=1486): 

Nurses’ Health Study: bad fats are associated with worse performance among diabetics (n=1486) Difference in Performance (Global Score) Sat. fat -0.12 (-0.22, -0.01) P:S ratio 0.08 (0.01, 0.16) Trans fat -0.15 (-0.24, -0.06)

Summary: Fat intake: 

Summary: Fat intake Still limited data re: cognition and dementia Cardiovascular health : low in saturated and trans fatty acids and high in monounsaturated and polyunsaturated (fish) fats, especially omega-3 Randomized trial data are not available

Slide34: 

ALCOHOL INTAKE

Alcohol: Mechanism: 

High intake of alcohol  adverse Neurotoxic at higher doses to brain structures Light to moderate drinking  protective Increases “good” cholesterol Decreases platelet adhesiveness Protects against heart disease, stroke Wine: flavonoids act as antioxidants Alcohol: Mechanism

Alcohol and Dementia: Rotterdam Study: 

Alcohol and Dementia: Rotterdam Study Ruitenberg et al., Lancet, 2002 Hazard Ratio

Other Evidence: 

Other Evidence Honolulu Asia Aging Study: 3,556 men age 71-93 years who had been followed for 18 years Drinkers up to 1/day had better scores than non-drinkers, but 4+/day was associated with cognitive impairment Columbia Aging Study: 980 people without dementia studied for 4 yrs Light to moderate (1-3 /day) pattern: reduced risk by 40%

Nurses’ Health Study: 

Nurses’ Health Study Participants 12,480 subjects at baseline 11,102 with follow-up cognitive data Measurement of alcohol intake Administered 1980, 84, 86, 90, 94, 98 Frequency of wine, liquor, beer consumption

Slide39: 

Risk of Substantial Cognitive Decline by Alcohol Stampfer et al., NEJM, 2005

Summary: Alcohol intake: 

Summary: Alcohol intake Consistent associations with moderate alcohol intake in observational studies Randomized trials unlikely Pay attention to health risks (may overshoot with excessive intake) However, if current consumption is 1-2 drinks a day, there should be no need to reduce (if no other medical reason to reduce)

Summary: 

Summary To date, preliminary data show nutrition is a promising research focus in cognitive aging Future research directions Mediterranean diet pattern Carbohydrate balance and the glycemic index Gene-diet interactions (e.g., types of fat and apolipoprotein E genotype)

Summary: 

Summary Overall, we need more studies of preventive approaches, including diet UNTIL THEN - get 5 servings of fruits & vegetables a day - lay off sweets and eat more whole grains - consume heart-healthy fats - don’t stop light to moderate drinking

Acknowledgements: 

Acknowledgements Advisors, Mentors, Colleagues Francine Grodstein Olivia Okereke Elizabeth Devore Meir Stampfer