DFA: EPA/DHA and Cognitive Health (2011)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The aim of the present study was to examine whether intake of different types of fatty acids is associated with cognitive status.

Inclusion Criteria:
  • Participants in an ongoing prospective study on the association between diet, antioxidant status and mortality
  • Institutionalized elderly population of Asturias (Northern Spain).
Exclusion Criteria:
  • Previous diagnosis of cancer, cardiovascular disease and related pathologies (such as diabetes, renal disease or stroke)
  • Neurological impairment
  • Terminal disease compromising longevity according to medical histories
  • Confined to a wheelchair.
Description of Study Protocol:


  • Participants in an ongoing prospective study
  • Institutionalized.



Blinding used

Not applicable


None. Comparison groups were various measures of lipid and fatty acid intake.

Statistical Analysis

  • Kolmogorov-Smirnov tests were performed to check that the distribution of variables followed a Gaussian pattern
  • When variables were not normally distributed or the variance of errors was not constant across factor levels (i.e. heteroskedasticity), variables were transformed by taking the natural logarithm before performing statistical comparisons
  • Significance of differences between means was calculated by multivariate analysis of variance to allow for covariate adjusting
  • Differences between proportions were examined using the chi-square test
  • Logistic regression models were conducted in order to estimate the odds ration (OR) for cognitive decline (MMSE score <24) per one-standard deviation (1-SD) increase in intake of fat and different fatty acids
  • The level of significance was set to P≤0.05. 
Data Collection Summary:

Timing of Measurements

  • One time point of measurement
  • Year time frame for the overall study was not given.

Dependent Variables

Global cognitive function: tested with the Spanish version of the Mini-Mental State Examination (MMSE) which is sensitive to moderate cognitive decline and which includes questions on orientation in time and place, registration, attention and calculation, recall, language and visual construction. A cut-off point of 24 (out of max 35 points) was used as it is indicative of cognitive impairment in a geriatric population. Slight deterioration: 20-24 points; mild dementia 15-19 points; severe dementia <15 points.

Independent Variables

  • Dietary factors: energy intake; lipid intake; SFA; MUFA; PUFA; n-6 PUFA; n-3 PUFA; LNA; EPA; DHA; n-6/n-3 PUFA ratio; fish and fish products
  • Intake was assessed by determination of the average frequency of each food offered by the institution, after they had provided the investigators with the menus of the previous year, so that estimation of the food frequency consumption does not depend upon the participant's memory. Trained dietitians asked each kitchen chef about cooking practices and the number and amount of ingredients used in each recipe, as well as questions concerning menu preparation (such as type of oil used, type of milk, etc.).
  • During interviews, subjects were asked item by item whether they usually ate each food and, if so, how much of it they were accustomed to eating. Three different serving sizes of each cooked food were presented in pictures to the participants, so that they could choose from up to seven serving sizes (from 'less than the small one' to 'more than the large one'). For some of the foods consumed, amounts were recorded in household units, by volume or by measuring with a ruler. All subjects were asked whether they had access to foods other than those being offered the institution (e.g. through their relatives).
  • Food intake was analyzed for energy and nutrient contents using the nutrient database developed by the EPIC group of Spain.

Control Variables

 Life-quality parameters: Physical activity; years of schooling; smoking habits; alcohol consumption.

Description of Actual Data Sample:
  • Initial N: 304
    • 127 men
    • 177 women
  • Attrition (final N): 304
  • Age:
    • MMSE <24 (N=90): 75.4±6.4 (71.1% female)
    • MMSE ≥24 (N=214): 75.3±6.9 (52.8% female)
  • Ethnicity: Not given
  • Other relevant demographics: Education (less than six schooling years)
    • MMSE <24: 60.0%
    • MMSE ≥24: 36.4% 
      • Inactive
        • MMSE <24: 43.3%
        • MMSE ≥24: 28.9%
      • Current smokers
        • MMSE <24: 17.0%
        • MMSE ≥24: 23.0
      • Alcohol consumers
        • MMSE <24: 31.1%
        • MMSE ≥24: 47.2%
      • Medication usage
        • Anti-anxiety (26%)
        • Anti-hypertensive (19.3%)
        • Analgesics (8.6%)
        • Diuretics (5.6%)
        • Asthma drugs (6.3%)
  • Anthropometrics: No information given
  • Location: Institutionalized elderly in Austurias (Northern Spain).


Summary of Results:

Key Findings

  • Intake of total n-3 PUFA, EPA, DHA and alpha-linolenic acid (LNA) were higher in the group of elderly with a higher cognitive score while the ratio n-6/n-3 PUFA ratio was lower in this group Borderline significance for LNA (P=0.065) and fish intake (P=0.079)
  • No differences with respect to cognitive function were found for total energy, lipids, SFA, MUFA, PUFA, or n-6 PUFA intake
  • Intakes of EPA and DHA were found to be predictors of cognitive impairment as they were negatively associated with cognitive score (odds ratio=0.70 [95% CI 0.503-0.973] and 0.71 [95% CI 0.507-0.993] per 1-SD increase in intake, respectively); on the contrary, the n-6/n-3 PUFA ratio was positively related to cognitive impairment (odds ratio=1.433 [95% CI 1.028-1.998] per 1-SD increase intake).
Variables MMSE<24 MMSE≥24 P-value
n-6 PUFA (grams per day) 16.35±5.16  16.70±3.99  0.55 
n-3 PUFA (grams per day) 1.294±0.58  1.430±0.57  0.03 
LNA (grams per day) 0.477±0.15  0.524±0.22  0.06 
EPA (grams per day) 0.238±0.18  0.283±0.19  0.05 
DHA (grams per day) 0.543±0.63  0.631±0.54  0.04 
n-6/n-3 PUFA ratio 16.10±10.26  12.93±5.71  0.001 
Fish and fish products grams per day 78.57±44.00  87.20±40.09  0.079 

Other Findings

Compared with subjects with MMSE ≥24, those with MMSE <24 were more likely to be female, to have less than six years of education, to be inactive and to not be alcohol consumers.

Author Conclusion:

Limitations cited by authors.

  • Cross-sectional nature of data and further research based on longitudinal studies is needed
  • Participants were people living in institutions with generally healthier behaviors, so the findings may not be generalizable to all elderly populations
  • Residual confounding by unmeasured or imprecisely measured factors cannot be excluded
  • High levels of consumption of EPA and DHA should be encouraged for reducing the risk of cognitive decline and subsequent disability in elderly people.
Funding Source:
Government: Fondo de Investigaciones Sanitarias
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? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? No
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  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? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  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? No
  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? No
  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? Yes
  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? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  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? N/A
  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? N/A
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