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

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


1
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 Womens Hospital, Boston MA
  • May 21, 2007

2
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

3
Objectives
  • Four topic areas
  • Fruits, vegetables, and antioxidants
  • Fat consumption
  • Insulin and diets that promote insulin resistance
  • Moderate alcohol intake

4
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
5
FRUIT, VEGETABLE AND ANTIOXIDANT INTAKE
6
Antioxidants Background
  • Oxidants
  • Products of normal aerobic metabolism and the
    inflammatory response
  • Oxidative damage in Alzheimers disease
  • One of the earliest pathophysiologic events

7
How might antioxidants prevent Alzheimers?
  • Reduce free radicals that harm brain cells
  • Decrease the toxicity of the amyloid protein
  • Lower cardiovascular disease risk

8
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

9
Antioxidants Epidemiological studies
  • Several studies have shown that higher intake of
    antioxidants, is associated with a lower risk of
    cognitive decline and Alzheimer disease

10
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
11
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

12
NHS Measurement of Fruit Vegetable Intake and
Cognitive Function
2nd cognitive assessment
1st cognitive assessment
Start 80 84 86
90 94 98 03
of NHS Dietary Assessment
using Food Frequency Questionnaires
13

NHS Measurement of Fruit Vegetable Intake
  • 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

14
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

15
Chicago Health and Aging Project confirms finding
with vegetables
Morris et al 2006 Neurology
16
ANTIOXIDANTS ROTTERDAM STUDY
RATE RATIO OF ALZHEIMERS DISEASE
TERTILE OF VITAMIN E INTAKE
Engelhart et al., JAMA, 2000
17
ANTIOXIDANTS ROTTERDAM STUDY
RATE RATIO OF ALZHEIMERS DISEASE
TERTILE OF VITAMIN C INTAKE
Engelhart et al., JAMA, 2000
18
NHS Vitamin E and C users, compared with
non-users




TICS
10-word immed
10-word delayed
EBMT immed
EBMT delayed
Fluency
Digit span
Global score
Grodstein et al, Am J Clin Nutr, 2003
19
Petersen et al, N Engl J Med, 2005
20
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?

21
INSULIN AND PROMOTERS OF INSULIN RESISTANCE
22
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

23
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

24
Mean Differences in Cognitive Function, by
C-peptide Quartile
VERBAL MEMORY
GLOBAL SCORE
0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0
0 -0.5 -1.0 -1.5
Q1 Q2 Q3 Q4
Q1 Q2 Q3 Q4
Okereke et al., Arch Intern Med, 2005
25
Relative Risk of Poor Cognitive Performance, by
C-peptide Quartile



QUARTILE OF PLASMA C-PEPTIDE
Okereke et al., Arch Intern Med, 2005
26
FAT INTAKE
27
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

28
  • Columbia Aging Project


Luchsinger et al.,Arch Neurol,2002
29
  • Chicago Health and Aging Project

Morris et al., Arch Neurol, 2003
30
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 RR0.4 (CI 0.2-0.9)
  • Highest intake of omega-3 fatty acids vs. lowest
    RR0.4 (CI 0.1-0.9)

Morris et al, Arch Neurol 2003
31
Fat Intake Rotterdam Study
Engelhart et al., Neurology, 2002
32
Nurses Health Study bad fats are associated
with worse performance among diabetics (n1486)
  • Difference in Performance (Global
    Score)
  • Sat. fat -0.12 (-0.22, -0.01)
  • PS ratio 0.08 (0.01, 0.16)
  • Trans fat -0.15 (-0.24, -0.06)

33
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

34
ALCOHOL INTAKE
35
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

36
Alcohol and Dementia Rotterdam Study
Hazard Ratio
Ruitenberg et al., Lancet, 2002
37
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

38
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

39
Risk of Substantial Cognitive Decline by Alcohol
Stampfer et al., NEJM, 2005
40
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)

41
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)

42
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
  • - dont stop light to moderate drinking

43
Acknowledgements
  • Advisors, Mentors, Colleagues
  • Francine Grodstein
  • Olivia Okereke
  • Elizabeth Devore
  • Meir Stampfer
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