• Increase Font Size
  • Decrease Font Size
  • View as PDF

FNOA: Antioxidants (2011-2012)

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

To determine whether supplement use of vitamins C and/or E in a community-based sample of older African-Americans and white individuals delayed incident dementia or Alzheimer's Disease (AD).

Inclusion Criteria:

Participants in the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) project.

Exclusion Criteria:

Those with dementia at baseline.

Description of Study Protocol:

Recruitment

The Duke EPESE sample was selected using a four-stage stratified household sampling design. Community residents ≥65 years old living in a five-county urban and rural area of the Piedmont, NC were included.

Design

Prospective cohort study

Blinding used

Not applicable

Intervention

Not applicable

Statistical Analysis

Bivariate analysis were used to determine the unadjusted association at baseline of antioxidant vitamin use and each of the independent variables with incident dementia using Cox proportional hazards.

 

Data Collection Summary:

Timing of Measurements

  • This study ran from 1986-1987 to 1996-1997
  • In-person interviews were held at the participant's home at baseline and three, six and 10 years later using structured questionnaires. Information gathered included demographic characteristics, health insurance status, health condition and behaviors, functional status, health service use, use of prescription and over-the-counter medications, and level of cognitive functioning as determined by the Short Portable Mental Status Questionnaire (SPMSQ).

 Dependent Variables

  • Presence of dementia as measured by SPMSQ scores and confirmed by a diagnosis consensus committee
  • Participants were evaluated by trained personnel using standardized procedures to ascertain the presence and type of dementia. A diagnosis consensus committee reviewed all data, relying on Diagnostic and Statistical Manual of Mental Disorders and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria for Alzheimer's Disease. A stratified random sample was drawn based on SPMSQ scores.

Independent Variables

  • Intake of vitamins C and E
  • At each of the four interviews, participants were asked to show the interviewer all drugs taken during the previous two weeks, including those prescribed by a physician and OTC medicines. The researches combined use of any vitamin C with any vitamin E, classifying use in a multivitamin preparation as low-dose and single supplement use of either vitamin C or vitamin E as high dose.

Control Variables

  • Age
  • Education
  • Gender
  • Marital status
  • Income
  • Health status as measured by self-reported HTN, myocardial infarction, stroke, diabetes and cancer (excluding skin cancer)
  • Body mass index
  • Severe depressive symptomatology as measured as at least nine endorsements on the Duke EPESE version of the Center for Epidemiologic Studies-Depression
  • Functional status as measured by Katz Activities of Daily Living Scale and the abbreviated three-item Rosow-Breslau scale
  • Alcohol use
  • Smoking
  • Use of drugs that reduce risk of adverse events
  • Health service use as measured by the number of outpatient visits in the last 12 months, number of prescription drugs, and number of over-the-counter drugs excluding vitamins and minerals.

  

Description of Actual Data Sample:
  • Initial N: The original Duke EPESE study included 4,162 participants
    • A subsample of 653 members were evaluated, and 37 had dementia at baseline and were excluded from the study. Therefore the initial n was 616. 
    • There were 475 in the group with no dementia and 141 in the group with incident dementia
    • The group with no dementia was 62.1% female, while the group with incident dementia was 63.8% female
  • Attrition (final N): No attrition was noted
  • Age: ≥65 at baseline
    • The group with no dementia's age was 72.3 (SD 6.2)
    • The group with incident dementia was 74.9 (SD 6.4)
  • Ethnicity:
    • The group with no dementia was 61.7% African American
    • The group with incident dementia was 63.8% African American
  • Other relevant demographics:
    • 43.2 percent of the group with no dementia was married
    • 33.6% of the group with incident dementia were married
    • 59.6% of the group with no dementia had income>$50,000
    • 51.1% of the group with incident dementia had income>$50,000
    • The group with no dementia has 8.3 years of education (SD 8.0)
    • The group with incident dementia had 7.4 years of education (SD 4.1)
  • Anthropometrics: Based on BMI:
    • 13.6 percent of the group with no dementia was underweight
    • 11.2 % of this group was overweight, as opposed to 15.0% underweight and 8.0% overweight for the group with incident dementia
  • Location: The Piedmont region of North Carolina.
Summary of Results:

Key Findings

  • Of the 616 sample members that were dementia-free, 141 developed dementia after baseline. Of these 141 persons, 93 were diagnosed with AD, 30 with vascular dementia, and 18 with other dementias, including dementia of unknown etiology.
  • Neither use of any dose nor of high-dose vitamins C and/or E at EPESE enrollment or later was significantly associated with risk of incident dementia of AD. At enrollment they reduced the risk of dementia, but not significantly.

Predictors of Incident Dementia and Alzheimer's Disease

Variable Predicting Demential Vit C and/or E Use, RR (95% CI)
Any		 Predicting Demential Vit C and/or E Use, RR (95% CI)
High Dose		 Predicting Demential Vit C and/or E Use, RR (95% CI)
Any		 Predicting Demential Vit C and/or E Use, RR (95% CI)
High Dose
Demographics
 Age,
  years		 1.05
(1.02 to 1.08)		 1.05
(1.02 to 1.08) 		 1.06
(1.02 to 1.09) 		 1.06
(1.02 to 1.10) 
 Education,
  years		 0.97
(0.92 to 1.04)		 0.97 
(0.93 to 1.01)		 1.01 
(0.96 to 1.07)		 1.01 
(0.96 to 1.07)
 Married 0.90
(0.69 to 1.49)		 0.90 
(0.60 to 1.33)		 0.92 
(0.56 to 1.52)		 0.92 
(0.56 to 1.51)
 Income 1.01
(0.69 to 1.49)		 1.02 
(0.70 to 1.50)		 0.89 
(0.54 to 1.46)		 0.91 
(0.56 to 1.50)
Functional Status
Rosow-Breslau 1.18
(1.00 to 1.39) 		  1.18
(1.00 to 1.39) 		  1.05
(0.85 to 1.30		  1.05
(0.85 to 1.30
Health Services Use
 0  reference  reference reference  reference 
 1-4  0.65
(0.43 to 0.99)		  0.66
(0.44 to 0.99)		 0.88  
(0.69 to 1.12)		  0.88
(0.69 to 1.13)
 at least 5  0.52
(0.32 to 0.86)		  0.53
(0.32 to 0.87)		  0.47
(0.20 to 1.10)		  0.48
(0.21 to 1.14)
Prescription drugs
 0  reference reference  reference  reference 
 1-4  0.94
(0.79 to 1.12) 		 0.94
(0.79 to 1.12) 		 0.88 
(0.69 to 1.12)		 0.88 
(0.69 to 1.13)
 at least 5  0.54
(0.28 to 1.06)		  0.55
(0.29 to 1.07)		  0.47
(0.20 to 1.10)		  0.48
(0.21 to 1.14)
Vitamin Use      
 at EPESE
 enrollment		 0.80
(0.40 to 1.58) 		 0.46
(1.11 to 1.89) 		 0.83
(0.36 to 1.92) 		  0.32
(0.04 to 2.31)
 wave prior
 to 
 diagnosis		  1.14
(0.64 to 2.03)		  0.65
(0.20 to 2.05)		 1.48
(0.78 to 2.81) 		  0.58
(0.14 to 2.39)

Other Findings

  • Higher age and poor mobility were risk factors for incident dementia
  • Use of more prescription medicines delayed dementia
  • Increased education, greater income, and being married reduced the risk of developing dementia.

 

Author Conclusion:

The authors conclude that in the southeastern United States where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or Alzheimer's Disease.

Funding Source:
Government: National Institute on Aging, National Institute of Allergy and Infectious Diseases
University/Hospital: Duke University, University of Pittsburgh, University of Minnesota
Reviewer Comments:
  • Only a small proportion (<10%) of the sample used vitamin supplements
  • The exact dose of vitamins C and E were not specified in this study, only classified as "low dose" or "high dose" based on self-reporting, which is subject to reporting error
  • Intake of vitamins C and E was obtained for the two-week period prior to the four interviews with subjects, rather than the "usual" or "normal" supplement intake over a more extended period of time
  • No data was collected on dietary intake of vitamin C or vitamin E. Intake from diet and supplements combined could change the results of the study.
  • There were differences in the baseline demographics of those with no dementia vs. those with dementia, particularly in the areas of use of health services, use of prescription drugs and use of OTC drugs.
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? 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? ???
  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.) 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? N/A
  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? 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.) No
  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? No
  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? No
  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? 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