DFA: EPA/DHA and Cognitive Health (2011)
Bargerger-Gateau P, Raffaitin C, Letenneur L, et al. Dietary patterns and risk of dementia: The Three-City Cohort study. Neurology. 2007; 69: 1,921-1,930.

To analyze the relationship between dietary patterns and risks of dementia or Alzheimer disease (AD), adjusting for sociodemographic and vascular factors, and taking into account the ApoE genotype.
- Living in the cities of Bordeaux, Dijon and Montpellier, France at the baseline in 1999 to 2000 and registered on the electoral roles
- Aged 65 or older
- Not institutionalized.
- Participants who refused to participate in baseline medical interview
- 215 demented participants were excluded at baseline
- By the second round of the study, 212 were deceased and 947 refused or were lost to follow-up
- By the third round, the cumulative number of deaths was 552 and 1,472 refused or were lost to follow-up.
Recruitment
Eligible participants were invited to participate in the study.
Design
- A brief food frequency questionnaire was administered at baseline to assess dietary habits. Other variables collected included:
- Sociodemographic information
- Vascular risk factors
- ApoE gentotyping
- Participants were screened for dementia.
Statistical Analysis
- The univariate associations between each food or oil and risk of dementia or AD over the four years of follow-up by proportional hazards model with delayed entry and age as time scale. For each food whose association with risk of dementia or AD was significant at a P<0.25 level, analyses were then adjusted for:
- Model one: Sociodemographic characteristics (age already taken into account by the model, gender, education, city, income and marital status
- Model two: ApoE genotype (in addition to the previous covariates)
- Model two: The previous covariates and all vascular risk factors that were themselves associated with risk for dementia with P<0.25 in multi-variate models adjusted for age, gender, education, and city
- Interactions between food sources of omega-3 and food sources of antioxidants were tested, as well as interactions between food sources of omega-3 or omega-6 and ApoE genotype. When a statistically significant interaction at P<0.10 was detected, stratified analyses were conducted.
- Various models testing the independent effect of each food by putting together a single model of all foods associated with dementia risk was also tested
- Statistical analyses were performed using SAS statistical package 9.1.
Timing of Measurements
- Baseline measurements in 1999 to 2000
- Follow-up measurements over the next four years.
Dependent Variables
Dementia: Determined by neuropscyhological tests and examination by a neurologist.
Independent Variables
- Nutrition variables: Food frequency questionnaire
- Sociodemographic information: Recorded information
- Vascular risk factors measured:
- Smoking
- Hypertension
- Diabetes
- Hypercholesterolemia
- Body mass index
- ApoE genotyping.
- Initial N: 9,693
- Attrition (final N): 8,085 (89.1%) had at least one follow-up examination over the four years
- Age: Over age 65 at baseline
- Ethnicity: French
- Anthropometrics: Not stated in this study; reported in other studies by this group
- Location: Bordeaux, Dijon and Montpellier, France.
Key Findings
- Daily consumption of fruits and vegetables was associated with a decreased risk of all cause dementia in fully adjusted models
- Weekly consumption of fish was associated with a reduced risk of AD and all-cause dementia but only among ApoE ε4 non-carriers
- Regular use of omega-3-rich oils was associated with a decreased risk of borderline significance for all-cause dementia
- Regular consumption of omega-6-rich oils not compensated by consumption of omega-3-rich oils or fish was associated with an increased risk of dementia.
Association Between Food and Risk of All-cause Dementia: The Three-City Cohort Study, 1999 to 2004
Model One, N=7,783 HR (95%CI) |
P |
Model Two, N=7,427 HR (95% CI) |
P |
Model Three, N=7,369 HR (95% CI) |
P | |
Fruit and vegetable frequent consumers |
0.70 (0.53 to 0.92) | 0.01 | 0.71 (0.53 to 0.95) | 0.02 | 0.72 (0.53 to 0.97) | 0.03 |
Butter | 0.87 (0.68 to 1.12) | 0.28 |
0.85 (0.65 to 1.10) |
0.21 |
0.86 (0.66 to 1.13) |
0.28 |
Vegetaline | 0.29 (0.04 to 2.05) | 0.21 |
0.30 (0.04 to 2.15) |
0.23 |
0.33 (0.05 to 2.36) |
0.27 |
Goose or duck fat | 1.24 (0.69 to 2.23) | 0.47 | 1.06 (0.56 to 2.01) | 0.86 | 1.00 (0.51 to 1.97) | 0.99 |
Olive oil | 0.83 (0.64 to 1.09) | 0.18 | 0.85 (0.64 to 1.13) | 0.27 | 0.84 (0.63 to 1.13) | 0.25 |
Omega-3-rich oil | 0.41 (0.17 to 0.995) | 0.049 | 0.45 (0.19 to 1.10) | 0.08 | 0.46 (0.19 to 1.11) | 0.08 |
Sunflower or grape seed oil | 1.20 (0.94 to 1.53) | 0.15 | 1.13 (0.88 to 1.46) | 0.35 | 1.16 (0.89 to 1.50) | 0.98 |
Model one: Proportional hazard models adjusted for age, gender, education, city, income and marital status.
Model two: Model one plus additional adjustment for ApoE genotype (possession of the ε4 allele).
Model three: Model two plus additional adjustment for body mass index and diabetes.
Association Between Food and Risk of Alzheimer Disease: The Three-City Cohort Study, 1999 to 2004
Model One, N=7,783 HR (95%CI) |
P |
Model Two, N=7,427 HR (95% CI) |
P |
Model Three, N=7,369 HR (95% CI) |
P | |
Fruit and vegetable frequent consumers | 0.70 (0.49 to 0.997) | 0.048 | 0.72 (0.50 to 1.04) | 0.08 | 0.73 (0.50 to 1.05) | 0.09 |
Butter | 0.83 (0.61 to 1.13) | 0.24 |
0.78 (0.56 to 1.07) |
0.12 | 0.77 (0.55 to 1.06) | 0.11 |
Goose or duck fat | 1.43 (0.72 to 2.83) | 0.30 | 1.13 (0.52 to 2.45) | 0.75 | 1.08 (0.47 to 2.48) | 0.85 |
Olive oil | 0.84 (0.61 to 1.18) | 0.32 | 0.90 (0.63 to 1.28) | 0.55 | 0.89 (0.62 to 1.28) | 0.53 |
Omega-3-rich oil | 0.40 (0.13 to 1.25) | 0.12 | 0.44 (0.14 to 1.37) | 0.16 | 0.43 (0.14 to 1.35) | 0.15 |
Sunflower or grape seed oil | 1.18 (0.87 to 1.60) | 0.29 | 1.12 (0.81 to 1.54) | 0.49 | 1.18 (0.85 to 1.63) | 0.33 |
Model one: Proportional hazard models adjusted for age, gender, education, city, income, and marital status.
Model two: Model one plus additional adjustment for ApoE genotype (possession of the ε4 allele).
Model three: Model two plus additional adjustment for body mass index and diabetes.
Frequent consumption of fruits and vegetables, fish and omega-3-rich oils may decrease the risk of dementia and Alzheimer disease, especially among ApoE ε4 non-carriers.
Government: | French National Agency for Research, Institut de la Longevite, Regional Councils of Aquitaine and Bourgogne, Foundation de France, and Ministry of Research | ||
Industry: |
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University/Hospital: | Institut de Sante Publique et Developpement of the Victor Segalen Bourdeaux 2 Univeristy, |
Quality Criteria Checklist: Primary Research
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Relevance Questions | |||
1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
2. | Was the selection of study subjects/patients free from bias? | Yes | |
2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | ??? | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
3. | Were study groups comparable? | N/A | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | N/A | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | N/A | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | N/A | |
3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | Yes | |
3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
4. | Was method of handling withdrawals described? | Yes | |
4.1. | Were follow-up methods described and the same for all groups? | Yes | |
4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawals similar across groups? | Yes | |
4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
5. | Was blinding used to prevent introduction of bias? | Yes | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | N/A | |
5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | N/A | |
5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | Yes | |
5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | N/A | |
6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | N/A | |
6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | N/A | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | N/A | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | N/A | |
6.6. | Were extra or unplanned treatments described? | N/A | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | N/A | |
6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
7.7. | Were the measurements conducted consistently across groups? | Yes | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | N/A | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | Yes | |
8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | Yes | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | Yes | |
10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |