FNOA: Antioxidants (2011-2012)

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

To determine the association between the trace elements of aluminum, calcium, cadmium, copper, iron, lead and zinc and cognitive function.

Inclusion Criteria:

2,000 Chinese persons 65 years or older from four counties in China that participated in a large cohort study of rural elderly Chinese persons.

Exclusion Criteria:

Those who were hearing impaired.

Description of Study Protocol:

Recruitment

Investigators went door-to-door and enrolled eligible residents. Informed consent was obtained before the interview and biological sample collection. Fasting blood samples from a random 10% of participants were collected.

Design

Cross-sectional analysis of a cohort  

Blinding used

Implied with laboratory measures 

Intervention

Not applicable 

Statistical Analysis

  • Participants' characteristics were compared between those who had trace element measures and those who did not have trace element measures using Student's T test for continuous variables and Fisher's exact test for categorical variables
  • To minimize floor and ceiling effects and other sources of measurement error, a composite score from all cognitive tests was created using the average of the six cognitive tests
  • Shapiro-Wilk test was used to test the normality assumptions of the composite z score
  • Cronbach's alpha was used to examine whether the composite score appropriately summarized the performances of all individual cognitive tests
  • Analyses of covariance (ANCOVA) models were used to examine the associations between each trace element and the composite z score adjusting for covariates
  • Because many participants' cadmium levels reached the lower detection limit, participants were grouped into low and high groups
  • The ANCOVA model was used to examine whether composite z scores were different between the two cadmium groups controlling for a set of covariates
  • For each trace element, quadratic effect models were fitted to detect a potential nonlinear association between the trace element level and the composite z score
  • Additional ANCOVA models were also conducted examining interaction effects between any two of the seven trace elements in a pairwise fashion.

     

Data Collection Summary:

Timing of Measurements

December 2003 to May 2005 

Dependent Variables

Cognitive assessments:

  • Community Screening Instrument for Dementia (CSID)
  • Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test
  • CERAD Word List Recall Test
  • Indiana University (IU) Story Recall
  • Animal Fluency Test
  • IU Token Test. 

Independent Variables

Levels from plasma blood samples of aluminum, calcium, cadmium, copper, iron, lead and zinc

Control Variables

  • Age
  • Sex
  • Ever attended school
  • Body mass index (BMI)
  • Systolic blood pressure
  • Diastolic blood pressure
  • APOE ε4 carrier
  • Alcohol consumption
  • Smoking status
  • History of cancer, Parkinson' disease, diabetes, hypertension, stroke, heart attack, head injury and fracture.
Description of Actual Data Sample:
  • Initial N: 201 (a random 10% of participants)
  • Attrition (final N): 188
  • Age Mean age: 69.2±4.1 years
  • Ethnicity: Chinese
  • Other relevant demographics
    • 50% female
    • 17.5% APOE ε4 carriers
  • Anthropometrics: 
    • BMI: 22.9±3.5
    • 46.8% ever attended school
  • Location: Sichuan and Shandong, China.

 

Summary of Results:

Key Findings

Results for Trace Elements

  • The composite z score in the subsamples with trace element measure had an approximately normal distribution (P=0.5319) and ranged from -1.872 to 2.377 (mean 0.25; standard deviation [SD]0.74) with higher scores indicating better cognitive function.
  • Cronbach's alpha was 0.84 indicating that the composite z score adequately summarized results of the individual tests
  • ANCOVA models examined the association between each trace element and the composite z score adjusting for age, gender, education, APOE genotype and BMI 
  • Three trace elements, calcium, cadmium and copper were found to be significantly related to the composite z score
  • Increasing plasma calcium level was associated with higher z score (P<0.0001). Increasing cadmium and copper were significantly associated with lower z score (P=0.0044 and P=0.0121, respectively).

Specific Results for Cadmium

  • Because there was a considerable number of participants reaching the lower detection limit on cadmium, participants were grouped into a low cadmium group and a high cadmium group
  • ANCOVA models revealed a significant difference between the mean z scores of the two groups while adjusting for age, gender, education, APOE genotype and BMI (P=0.0247).

 

Author Conclusion:

In this subsample of a large Chinese cohort of elderly participants, a significant association was found between increasing plasma calcium levels and higher cognitive function scores. It was also identified that plasma cadmium and copper levels were associated with lower cognitive scores.

Previous studies on calcium and cognitive function had reported positive or quadratic association between calcium in drinking water and cognitive function. A limitation of these studies is that individual biological calcium levels were not available. The association between plasma copper level and cognitive score was consistent with previous findings. Previous observational studies on cadmium and cognitive function in adults and elderly populations were inconsistent.

 

Funding Source:
Government: National Institutes of Health
Reviewer Comments:

This study had a number of strengths:

  • Trace elements were measured in plasma samples so that measurement errors from dietary recalls were eliminated
  • The participants were lifelong residents in their villages and they were not taking dietary supplements, so their biological measures reflect intake from food and water sources and remain relatively stable
  • Multiple cognitive tests were used, so that the composite score reliably reflects the global cognitive function from multiple contrive domains.

The author notes the following limitations:

  • Blood samples were collected from only a small fraction of the study participants in the cohort
  • Participants who consented to blood collection tended to be younger, more educated and to have higher BMI values than those who did not donate blood samples
  • They did not differ from the remaining cohort in other demographic, lifestyle or medical characteristics
  • It is possible that the range in some trace elements in the cohort could be limited because potential sites with high levels of toxic trace elements were excluded
  • Trace elements were measured in plasma samples and they may not have been sensitive to tissue-specific changes in trace element functioning.

 

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? No
  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? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  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? No
  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? 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? 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? 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