FNOA: Antioxidants (2011-2012)

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

To prospectively examine associations between intakes of antioxidants (vitamins C, vitamin E and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah.

Inclusion Criteria:
  • Cache County residents aged 65 years or older on January 1, 1995
  • All participants or their relatives in the case of impaired persons have written, informed consent to participate in the study.
Exclusion Criteria:
  • Subjects scoring below the cutoff for the 3MS did not receive a food frequency questionnaire
  • Implausible caloric intakes (less than 600 or greater than 5,000kcal per day)
  • Subjects having prevalent dementia after clinical assessment.
Description of Study Protocol:

Recruitment

  • Cache County Study on Memory, Health and Aging is a population-based longitudinal study of the prevalence and incidence of dementia among elderly residents of a single county in Utah
  • There were 5,677 permanent residents of Cache County aged 65 or older on January 1, 1995 (per Health Care Financing Administration records and local public relations efforts), of which 5,092 (90%) enrolled in the study and completed the baseline interview (1995-1996)
  • Additional follow-up surveys were conducted in 1997-1998, 1998-1999, and 2002-2003, and the average length of follow-up for those completing all waves of follow-up was 7.2 years.

Design

Prospective cohort study 

Blinding used

Not applicable 

Intervention

Not applicable 

Statistical Analysis

  • Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time
  • Associations were examined for nutrient intake from foods alone and for foods and supplements combined
  • All models included both linear and quadratic terms for time in order to account for curvilinear trajectories of 3MS performance over time
  • Intakes of the antioxidant nutrients were modeled as quartiles of intake
  • Interactions between the time variables and the nutrient variables of interest were tested by comparing the likelihood ratio test statistics between models with and without the interaction terms.
Data Collection Summary:

Timing of Measurements

  • In 1985, subjects completed a baseline survey that included a food frequency questionnaire and cognitive assessment, as well as information on demographic characteristics, health history, family history of dementia, use of medications, alcohol, tobacco, and other lifestyle factors
  • Cognitive function was assessed at baseline and at three subsequent follow-up interviews spanning approximately seven years
  • Participants were asked to provide a cheek-swab DNA sample test that was used for APOE genotyping
  • Baseline visit and follow-up visits 2 and 3 were conducted in person, while follow-up visit 1 was conducted over the phone.

Dependent Variables

Cognitive function assessed using an adapted version of the Modified Mini-Mental State examination (3MS)

Independent Variables

Antioxidant intake assessed through food frequency questionnaire

Control Variables

  • Age
  • Gender
  • Level of education (years of school completed)
  • APOE genotype
  • History of tobacco and alcohol use
  • Physical activity (indicator of vigorous physical activity at least once per week)
  • History of diabetes, myocardial infarction and stroke.
Description of Actual Data Sample:
  • Initial N: 3,831 subjects completed baseline survey
    • 74 excluded for implausible caloric intakes
    • 123 excluded for having prevalent dementia
  • Attrition (final N):  3,632 participants included in the analysis
    • 1,566 men
    • 2,066 women
  • Age:  Aged 65 years or older at baseline, mean age 74.6±6.7 years
  • Ethnicity: Not reported
  • Other relevant demographics: 
    • Mean education level of 13.3±2.8 years
    • 90% of participants are members of the Church of Jesus Christ of Latter-Day Saints
  • Anthropometrics:
  • Location: Cache County, Utah.

 

Summary of Results:

Key Findings

  • Participants consuming antioxidants in the higher quartiles of antioxidant intake (quartiles 2, 3 and 4) were more educated, scored higher on the baseline 3MS and were more likely to be female compared with participants in the lowest quartiles of antioxidant intake
  • Participants in the highest quartiles of each specific antioxidant were more likely to take that antioxidant in supplement form and had higher mean intakes of other antioxidants from both food and supplemental sources compared to participants consuming in the lowest quartiles of intake
  • Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (P for trend=0.013 and 0.02, respectively)
  • This association appeared stronger for food sources compared to supplement or food and supplement sources combined
  • Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake.

Multivariable adjusted average cumulative change in 3MS score by year of study follow-up across increasing quartile of intake of vitamin C, vitamin E and carotene among 3,632 subjects

 

Variables    1.5 years of follow-up Three years of follow-up  Seven years of follow-up  P-value 
Food Vitamin C Q1 -0.28  -0.99  -3.65  0.0015 
  Q2 +0.01  -0.50  -3.10   
  Q3 +0.03  -0.52  -3.33   
  Q4 +0.04  +0.08  -3.48   
Total Vitamin C Q1 -0.31  -0.95  -3.20  0.004 
  Q2 +0.08  -0.49  -3.56   
  Q3 +0.17  -0.34  -3.14   
  Q4 -0.10  -0.20  -3.77   
Food Vitamin E Q1 -0.06  -0.58  -2.97  0.0028
  Q2 +0.02  -0.54  -3.39   
  Q3 -0.24  -0.98  -3.94   
  Q4 +0.09  +0.19  -3.23   
Total Vitamin E Q1 -0.13  -0.69  -3.06  0.0022 
  Q2 -0.14  -0.80  -3.61   
  Q3 -0.05  -0.59  -3.10   
  Q4 +0.12  +0.24  -3.74   
Food Carotene Q1 -0.26  -0.92  -3.39  0.034 
  Q2 -0.15  -0.64  -2.70   
  Q3 +0.06  -0.47  -4.01   
  Q4 -0.29  +0.13  -3.49   
Total Carotene Q1 -0.29  -0.86  -2.86  0.011 
  Q2  +0.08  -0.42  -3.14   
  Q3  +0.002  -0.658  -3.97   
  Q4  +0.009  +0.018  -3.57   

 

 

Author Conclusion:

In summary, the findings from the Cache County Study, a large, population-based prospective study, provides evidence that higher intakes of antioxidants including vitamin C, vitamin E, and carotene from food alone or from food and supplements combined may help preserve cognitive function and thus delay cognitive decline in the elderly. Vitamin C intake from food, alone or in combination with vitamin E from food, seemed especially beneficial as participants with the highest intake had higher baseline 3MS scores and maintained higher function over the first three years of follow-up. Further longitudinal follow-up and study of food groups and dietary patterns may provide more insight into the role of antioxidant and other nutrients in maintaining cognitive function and preventing dementia in later life.

Funding Source:
Government: National Institute on Aging
Reviewer Comments:

Authors note the following limitations:

  • Results could be due to uncontrolled confounding
  • Homogeneous population may not be generalizable to other populations
  • Limited length of follow-up of 7.2 years and was conducted relatively late in life
  • Cognitive status is a broad concept and one test of global function, such as the 3MS used, may not provide a complete measure of cognitive function in the non-demented elderly
  • Selective survival may influence the results because dementia disorders and cognitive impairment are accompanied by an increased mortality.
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? ???
  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? ???
  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? 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? 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