FNOA: Antioxidants (2011-2012)
To prospectively examine flavonoid intake in relation to cognitive function and decline among subjects aged 65 years or older.
- Community dwellers aged 65 years or older
- Subjects free from dementia at baseline and with reliable dietary assessment.
Excluded if not included above.
Recruitment
- Subjects were part of the PAQUID (Personnes Agees Quid) study on functional and cerebral aging, which included at baseline 3,777 community dwellers aged 65 years or older
- Participants were randomly recruited from electoral rolls, and selection was stratified by sex, age, and size of the urban unit throughout Gironde and Dordogne, two administrative areas of southwest France
- The initial participation rate was 68% and the sample was representative of the age-sex distribution of the elderly community dwellers of the area.
Design
Prospective cohort study
Blinding used
Not applicable
Intervention
Not applicable
Statistical Analysis
- Univariate associations between flavonoid intake and explanatory variables were tested with the chi-square test or ANOVA when appropriate
- Linear mixed models were used to analyze the evolution of cognitive performance according to quartiles of flavonoid intake
- Each estimated parameter significance was tested by Wald's test and log-likelihood ratio tests were performed for tests for trend.
Timing of Measurements
- Participants were visited at home by a psychologist for the baseline interview in 1988-1989
- Subjects were reexamined four times over a ten-year period, at years three, five, eight, 10 and 13.
- Cognitive function assessed at each visit
- Flavonoid intake assessed at the three-year visit.
Dependent Variables
- Cognitive functioning assessed through psychometric tests
- Mini-Mental State Examination for global mental status
- Benton's Visual Retention Test for visual memory
- "Isaacs" Set Test for verbal fluency
- Zazzo's Cancellation Test for visuospatial attention
- Wechsler's Digit Symbol Test for simple logical reasoning and attention.
Independent Variables
Flavonoid intake estimated through food frequency questionnaire
Control Variables
- Age
- Sex
- Educational level
- BMI
- Smoking
- Quantity of fruits and vegetables consumed each day.
- Initial N: 3,777 subjects in original cohort. Food frequency questionnaire completed by 1,795 subjects.
- Attrition (final N): 1,640 non-demented subjects included in final analysis.
- 78 subjects with dementia were excluded
- 77 subjects had insufficient data on psychometric tests
- Age: Mean aged 76-77 years at baseline
- Ethnicity: Not reported
- Other relevant demographics:
- Anthropometrics:
- Location: France.
Key Findings
- Mean flavonoid intake was 14.33±5.85mg per day and the quartiles of flavonoid intake were zero-10.39, 10.40-13.59, 13.60-17.69, and 17.70-36.94mg per day
- BMI was not associated with flavonoid intake
- Mean MMSE score at baseline was 27.1±2.4 and increased as flavonoid intake increased, and the same pattern was observed for the other cognitive tests
- After adjustment for age, sex and educational level, flavonoid intake was associated with better cognitive performance at baseline (P=0.019) and with a better evolution of the performance over time (P=0.046)
- Subjects included in the two highest quartiles of flavonoid intake had better cognitive evolution than did subjects in the lowest quartile
- After 10 years' follow-up, subjects with the lowest flavonoid intake had lost on average 2.1 points on the Mini-Mental State Examination, whereas subjects with the highest quartile had lost 1.2 points, and this gradient persisted after adjustment for several other potential confounders.
Multivariate Model Estimates for Several Categories of Flavonoid Intake
Variables | Coefficient | Standard Error | Walds's Test P Value |
Intercept | 0.634 | 0.00974 | <0.001 |
Time | -0.00945 | 0.00129 | <0.001 |
Flavonoid (mg per day) | |||
Quartile 1 (0-10.39) | Referent | ||
Quartile 2 (10.40-13.59) | 0.00454 | 0.00644 | 0.48 |
Quartile 3 (13.60-17.69) | 0.0131 | 0.00656 | 0.046 |
Quartile 4 (17.70-36.94) | 0.0216 | 0.00658 | 0.0010 |
Flavonoid by time | |||
Quartile 1 x time | Referent | ||
Quartile 2 x time | 0.00195 | 0.00112 | 0.081 |
Quartile 3 x time | 0.00242 | 0.00116 | 0.037 |
Quartile 4 x time | 0.00296 | 0.00114 | 0.0097 |
In conclusion, we showed that higher intake of flavonoids from food may be associated with a better cognitive evolution over a 10-year period. Whether this reflects a causal association remains to be elucidated. We cannot exclude that the flavonoid intake measured in our study is a global marker of specific dietary habits that are more favorable for cognitive aging. Since flavonoids are found mainly in fruits and vegetables, subjects classified in the highest quartiles are likely to eat more fruits and vegetables that are known to be associated with a lower risk of several diseases, including cognitive decline. More cohort studies are needed to further investigate the relation between flavonoid intake and cognitive evolution, including other antioxidant molecules.
Government: | Conseil General de la Gironde, Conseil General de la Dordogne, Ministere de la Recherche et de la Technologie | |||
Industry: |
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Not-for-profit |
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Large representative cohort with 10 years of follow-up, but unclear if subjects included in the analysis were representative (1,640 subjects from original 3,777 in cohort). Flavonoid intake only assessed at one visit. Authors note the following limitations:
- Although we adjusted for several potential confounding factors, the possibility of residual confounding cannot be completely excluded
- Even in longitudinal studies, one cannot exclude the possibility of changing dietary reporting or dietary habits because of cognitive impairment
- Since dietary assessment was performed only once, it may not have precisely reflected the participant's long-term dietary habits.
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) | N/A | |
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) | N/A | |
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? | ??? | |
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? | ??? | |
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? | Yes | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
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? | ??? | |
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%.) | ??? | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawals similar across groups? | ??? | |
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? | N/A | |
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? | N/A | |
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? | Yes | |
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? | 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 | |