EAL

DFA: EPA/DHA and Cognitive Health (2011)

Citation:

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.

Study Design:

Prospective Cohort Study

Class:

B - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

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.

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Description of Study Protocol:

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.

Data Collection Summary:

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.

Description of Actual Data Sample:

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.

Summary of Results:

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.

Author Conclusion:

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.

Funding Source:

Government:

French National Agency for Research, Institut de la Longevite, Regional Councils of Aquitaine and Bourgogne, Foundation de France, and Ministry of Research

Industry:

Sanofi-Aventis

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

Institut de Sante Publique et Developpement of the Victor Segalen Bourdeaux 2 Univeristy,

Reviewer Comments:

Quality Criteria Checklist: Primary Research
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