Title: Does Diet Play a Role in Dementia Prevention Data From the Nurses Health Study
1Does 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
2Objectives
- 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
3Objectives
- Four topic areas
- Fruits, vegetables, and antioxidants
- Fat consumption
- Insulin and diets that promote insulin resistance
- Moderate alcohol intake
4Impact 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
5FRUIT, VEGETABLE AND ANTIOXIDANT INTAKE
6Antioxidants Background
- Oxidants
- Products of normal aerobic metabolism and the
inflammatory response - Oxidative damage in Alzheimers disease
- One of the earliest pathophysiologic events
7How might antioxidants prevent Alzheimers?
- Reduce free radicals that harm brain cells
- Decrease the toxicity of the amyloid protein
- Lower cardiovascular disease risk
8Where 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
9Antioxidants Epidemiological studies
- Several studies have shown that higher intake of
antioxidants, is associated with a lower risk of
cognitive decline and Alzheimer disease
10Fruits 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
11NHS 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
12NHS 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
14NHS 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
15Chicago Health and Aging Project confirms finding
with vegetables
Morris et al 2006 Neurology
16ANTIOXIDANTS ROTTERDAM STUDY
RATE RATIO OF ALZHEIMERS DISEASE
TERTILE OF VITAMIN E INTAKE
Engelhart et al., JAMA, 2000
17ANTIOXIDANTS ROTTERDAM STUDY
RATE RATIO OF ALZHEIMERS DISEASE
TERTILE OF VITAMIN C INTAKE
Engelhart et al., JAMA, 2000
18NHS 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
19Petersen et al, N Engl J Med, 2005
20Summary 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?
21INSULIN AND PROMOTERS OF INSULIN RESISTANCE
22Insulin 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
23Insulin 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
24Mean 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
25Relative Risk of Poor Cognitive Performance, by
C-peptide Quartile
QUARTILE OF PLASMA C-PEPTIDE
Okereke et al., Arch Intern Med, 2005
26FAT INTAKE
27Fat 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 Luchsinger et al.,Arch Neurol,2002
29- Chicago Health and Aging Project
Morris et al., Arch Neurol, 2003
30Consumption 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
31Fat Intake Rotterdam Study
Engelhart et al., Neurology, 2002
32Nurses 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)
33Summary 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
34ALCOHOL INTAKE
35Alcohol 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
36Alcohol and Dementia Rotterdam Study
Hazard Ratio
Ruitenberg et al., Lancet, 2002
37Other 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
38Nurses 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
39Risk of Substantial Cognitive Decline by Alcohol
Stampfer et al., NEJM, 2005
40Summary 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)
41Summary
- 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)
42Summary
- 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
43Acknowledgements
- Advisors, Mentors, Colleagues
- Francine Grodstein
- Olivia Okereke
- Elizabeth Devore
- Meir Stampfer