FNOA: Antioxidants (2011-2012)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • To assess the association between vitamin C and cognitive function
  • To examine potential confounding factors that were not previously considered, as well as examining gender as a potential effect modifier.
Inclusion Criteria:
  • Community-dwelling older adults aged 65 or older
  • Residents of Washington County, Maryland who participated in both the Cardiovascular Health Study (CHS) and CLUE II Study in 1989-1990
  • Able to give informed consent
  • Able to respond to questions without a proxy respondent.
Exclusion Criteria:
  • Participants who were wheel-chair bound at home, institutionalized, or undergoing cancer treatment were excluded
  • Participants missing more than one-third of the items pertaining to fruits and vegetable intake were excluded from the analysis.
Description of Study Protocol:

Recruitment

  • Participants in both the Cardiovascular Health Study (CHS) and the CLUE II Study in Washington County, Maryland 
  • Cardiovascular Health Study (CHS) is a population-based, prospective observational study designed to evaluate risk factors for coronary heart disease and stroke in community-dwelling individuals aged 65 and older; the original cohort was recruited from a random sample of Health Care Financing Administration (HCFA) Medicare eligibility lists, and eligible household members of those sampled, between 1989-1990.
  • Campaign against Cancer and Heart Disease (CLUE II) was a blood collection campaign conducted in 1989 in Washington County, Maryland; timing was concurrent with the baseline CHS examination
  • Linkage of CHS and CLUE II by date of birth and last name identified 544 older adults who had participated in both studies.

Design

Cross-sectional study 

Blinding used

Not applicable 

Intervention

Not applicable 

Statistical Analysis

  • Mann-Whitney test was used to assess differences in demographic, health status, and selected behavioral characteristics between persons with higher and lower cognitive function
  • Intakes and plasma concentrations were divided into fifths or thirds based on the distributions of vitamin C levels among participants with scores of 27 or greater on the MMSE
  • Unconditional logistic regression models were used to examine the crude and independent association between vitamin C and MMSE scores, adjusting for potential confounders
  • Multiple linear regression models were used for DSST because scores were normally distributed.
Data Collection Summary:

Timing of Measurements

  • Participants in both Cardiovascular Health Study (CHS) and CLUE II Study in 1989
  • Baseline CHS evaluation included standardized assessments of cognitive function, depressive symptoms, physical function, medication use, general health and health habits.

Dependent Variables

  • Cognitive function measured in CHS
    • Mini-Mental State Examination (MMSE)
    • Digit-Symbol Substitution Test (DSST) 
  • Trained interviewers administered cognitive tests under standardized conditions.

Independent Variables

  • Vitamin C intake assessed through 60-item food frequency questionnaire from CLUE II
  • Plasma vitamin C concentration assessed through blood samples taken in CLUE II.

Control Variables

  • Age
  • Education
  • Smoking history
  • Body mass index
  • Depressive symptomatology assessed using shortened version of the Center for Epidemiologic Studies Depression (CES-D) scale
  • Health status indicators included validated histories of stroke or transient ischemic attacks, hypertension, medication use, and report of visual impairment.
Description of Actual Data Sample:
  • Initial N: 544 older adults had participated in both CHS and CLUE II, completed the MMSE and had plasma vitamin C concentrations and were included in the study
  • Attrition (final N): 
    • 514 completed the DSST
    • 455 returned a completed food frequency questionnaire
  • AgeAged 65 or older
  • EthnicityAlmost all were Caucasians
  • Other relevant demographics:
  • Anthropometrics:
  • LocationWashington County, Maryland.

 

Summary of Results:

Key Findings

  • Individuals with higher MMSE or DSST scores (>27 and >30 points, respectively) had a significantly higher educational attainment, better health and less vision impairment
  • Participants who were female or were not married were more likely to have higher MMSE scores, but not higher DSST scores than men or married individuals
  • Participants with lower cognitive test scores were older, had more depressive symptoms, and higher BMI, though these differences were not always statistically significant
  • 3% of the subjects had low plasma vitamin C concentrations (<40mg/dL) and 15% had low total vitamin C intake (<60mg per day)
  • 40% were taking supplements containing vitamin C
  • Most participants (96.7%) had normal cognitive function
  • In unadjusted analyses, the highest fifth of plasma vitamin C concentration was associated with better Digit Symbol Substitution Test (DSST) scores and marginally associated with Mini-Mental State Examination (MMSE) compared to the lowest fifth
  • Total vitamin C intake, measured by Block's food frequency questionnaire, was generally associated with higher MMSE scores, though it was not significant
  • Adjusting for numerous factors did not substantially change results
  • In a stratified analysis by gender, higher plasma concentrations or intake were associated with higher MMSE scores for men but not for women
  • The main finding from this study is that the lowest fifth of plasma vitamin C concentrations was cross-sectionally associated with lower DSST scores compared to the highest fifth
  • The second finding is that higher vitamin C intake and plasma concentrations were associated with higher MMSE scores in men but not women.
Author Conclusion:

In summary, for the total population, there was no independent association between vitamin C with DSST or MMSE after adjusting for demographic factors, depressive symptomatology, body mass index, and smoking, although there was an association with DSST prior to adjustment. Higher vitamin C concentrations or intake were associated with better MMSE scores in men but not in women. Having more depressive symptoms was inversely associated with lower MMSE scores in women. Given the intriguing gender differential, future studies should consider gender as a potential effect modifier in considering risk factors for cognitive impairment.

Funding Source:
Government: National Heart, Lung and Blood Institute
Reviewer Comments:

Vitamin C status assessed through both dietary intake and plasma levels. All subjects from one county in Maryland. Authors note the following limitations:

  • Cross-sectional study design: It is difficult to determine whether low vitamin C levels preceded poor cognition or whether poor cognition caused changes in vitamin C intake
  • Other nutrients highly correlated with vitamin C could explain the observed results
  • Study was clearly dominated by highly cognitively able individuals, findings may not be generalizable
  • Only 3% had truly low plasma vitamin C concentrations.

 

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) 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? No
  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? 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? 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? 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? 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? Yes
  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