FNOA: Antioxidants (2011-2012)

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

To investigate cerebrospinal fluid markers of Alzheimer's disease (levels of cerebrospinal fluid Aβ42, Tau and Phospho-Tau) in correlation with copper, zinc and ceruloplasmin in plasma, copper, zinc and neurotransmitters in cerebrospinal fluid of Alzheimer's disease patients with normal cerebrospinal fluid biomarker levels and those with aberrant levels.

Inclusion Criteria:
  • Patients fulfilled all criteria including informed consent using the cognitive subscale score on the Alzheimer's Disease Assessment Scale (ADAS-cog score) and the Mini-Mental State Examination (MMSE)
  • Screening procedures included medical history, physical examination and psychometric tests.
Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Recruitment methods not described.

Design

Cross-sectional study 

Blinding used 

Implied with measurements 

Intervention 

Not applicable 

Statistical Analysis

  • Boxplots were examined to identify extreme values
  • Kolmogorov-Smirnov test was used to check normality assumption
  • Stepwise multiple linear regression with predictor variables age, disease duration and sex were performed
  • Multivariate analyses of covariance with independent variable diagnostic group adjusted for significant factors and covariates from the regression analyses were calculated separately for the six blocks of dependent variables, in case of significance followed by univariate tests
  • For each dependent variable results for factor diagnostic group were checked up with nonparametric Mann-Whitney U test.

 

Data Collection Summary:

Timing of Measurements

Blood samples collected.

Dependent Variables

  • Blood copper, zinc and ceruloplasmin determined by standard laboratory methods
  • Cerebrospinal fluid profiles of copper, zinc and neurotransmitters determined by standard laboratory methods.

Independent Variables

  • Cerebrospinal fluid biomarkers: 
    • Aβ42
    • Tau
    • Phospho-Tau determined by standard laboratory methods.

Control Variables

  • Age
  • Sex
  • Disease duration.
Description of Actual Data Sample:
  • Initial N: 29 patients, divided into two groups based on their level of cerebrospinal fluid biomarkers
  • Attrition (final N): 29 patients
    • No diagnosis of Alzheimer's disease in cerebrospinal fluid: 
      • 13 subjects, seven males, six females
    • Diagnosis of Alzheimer's disease in cerebrospinal fluid: 
      • 16 subjects, eight males, eight females
  • Age: 
    • No diagnosis of Alzheimer's disease in cerebrospinal fluid: Mean age 70 years
    • Diagnosis of Alzheimer's disease in cerebrospinal fluid: Mean age 73.19 years
  • EthnicityNot reported
  • Other relevant demographics:
  • Anthropometrics: There were no significant differences between groups in terms of age, disease duration, sex, ADAS-cog and MMSE.
  • Location: Germany. 

 

 

Summary of Results:

Key Findings

  • Multivariate tests revealed a significant effect of factor diagnostic group (no Alzheimer's disease diagnosis in cerebrospinal fluid or Alzheimer's disease diagnosis in cerebrospinal fluid) for variables plasma copper and ceruloplasmin (F=4.80, df=2, 23; P=0.018)
  • Subsequent univariate tests revealed significantly reduced plasma copper (-12.7%, F=7.05; df=1, 25; P=0.014) and ceruloplasmin (-14.1%, F=9.44, df=1, 24; P=0.005) levels in patients with aberrant cerebrospinal fluid biomarker concentrations.
Author Conclusion:

Although only Alzheimer's disease patients were included, the reduced plasma copper levels and ceruloplasmin levels in patients with a cerebrospinal fluid diagnosis of advanced Alzheimer's disease supports previous observations that a mild copper deficiency might contribute to Alzheimer's disease progression.

Funding Source:
Industry:
International Copper Association
Other:
University/Hospital: HOMFOR program of the Saarland University Medical Faculty
Not-for-profit
European Copper Institute, Deutsche Kupfer Institut
Foundation associated with industry:
Reviewer Comments:
  • Inclusion/exclusion criteria and recruitment methods not described
  • Only subjects with Alzheimer's disease were included
  • Dietary intake not assessed
  • Supported by the International Copper Association and European Copper Institute.
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? ???
  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.) Yes
  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%.) N/A
  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? Yes
  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.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? N/A
  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? No
  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)? ???
  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? No
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? No
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? No