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FNOA: Antioxidants (2011-2012)

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

To determine if alterations in serum zinc occur in the progression of Alzheimer's disease (AD).

Inclusion Criteria:
  • Men and women
  • Participant at the University of Kentucky Alzheimer's Disease Center
  • Mild to moderate probably AD or mild cognitive impairment (MCI).
Exclusion Criteria:

None specified.

Description of Study Protocol:

Recruitment

  • Cases were recruited from participants at the University of Kentucky Alzheimer's Disease Center
  • Controls were from a population of normal participants followed longitudinally in the healthy brain aging clinic of the University of Kentucky Alzheimer's Disease Center
  • Methods of recruitment were not disclosed. 

Design

  • Case-control study
  • Serum zinc samples were collected from participants and controls
  • Blood samples were also used for APOE-4 genotyping
  • Serum levels of zinc were evaluated in cases and controls to identify an pattern in level of zinc vs. progression of cognitive impairment
  • Subjects were classified as mild to moderate-probable AD (based on annual mental status testing and physical and neurological testing and meeting NINCDS-ADRDA Workgroup criteria for the clinical diagnosis of probable AD) and moderately cognitively-impaired (based on clinical criteria of memory complaints, objective memory impairment for age and education, intact general cognitive function, intact activities of daily living and lack of dementia)
  • Subjects were evaluated using the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating Scale (CDR).

Blinding Used

Implied with measurements.

Statistical Analysis

  • Subject demographic data were compared using ANOVA
  • A one-sample Kolmogorov-Smirnov test demonstrated serum Zn concentrations were normally distributed and Levene's Test for Equality of Variances demonstrated that the populations had equal variances
  • A linear model, Univariate: Two Facto ANOVA was used for comparison.
Data Collection Summary:

Timing of Measurements

No information on dates or timeframe of data collection or analysis was provided. 

Dependent Variables

  • Mild cognitive impairment, as measured by:
    • Memory complaints
    • Objective memory impairment for age and education
    • Intact general cognitive function
    • Intact activities of daily living (ADLs)
    • The subject is not demented.
  • Probable Alzheimer's disease as determined by NINCDS-ADRDA Workgroup criteria for the clinical diagnosis of probable AD.

Independent Variables

Serum zinc levels, as measured by coupled plasma mass spectrometry using a VG Axion ICP-MS.

Description of Actual Data Sample:
  • Initial N: 18 mild- to moderate-probable AD patients (nine men, nine women), 19 moderately cognitively-impaired patients (MCI, nine men, 10 women) and 16 normal controls (nine men, seven women)
  • Attrition (final N): No attrition
  • Age: The Control Group had an age of 77.9±1.7 years, MCI Group had a mean age of 78.4±1.6 years and the AD Group had a mean age of 80.3±1.7 years. Ages in the Control, MCI and Probable AD Group were not significantly different.
  • Ethnicity: No data provided
  • Other relevant demographics: No data provided
  • Anthropometrics: No data provided
  • Location: University of Kentucky, Lexington, KY.
Summary of Results:

Key Findings

  • Comparison of all subjects combined showed no significant differences in age or the number of APOE-4 alleles between the three groups
  • Serum zinc concentrations for all subjects showed no significant differences between the three groups
  • Serum zinc concentrations by gender showed a statistically-significant decrease of zinc in men with MCI, compared to control men (P=0.028). This rebounded to control levels in those with AD. Serum zinc levels between the three groups for women were not statistically different. Serum zinc was significantly lower in men with MCI, compared to women with MCI.
  • Correlation analyses showed serum zinc concentrations were positively-related to the number of APOE-4 alleles in men, but negatively related to the number of APOE-4 alleles in men with MCI and AD and all women. The correlations were not statistically significant.

Zinc Concentrations (mcM) in the Original Serum Samples by Groups

Group

 Male Female

Overall
Mean ±SE
M (mcM)

Mean ±SE
M (mcM)

Range (mcM)

Mean ±SE
M (mcM)

Range (mcM)
NC (9M, 7F)
13.9±0.6
10.9~17.3
12.5±1.0
9.5~16.6
13.3±0.6
MCI (9M, 10F)

11.7±0.5

9.6~14.2
13.7±0.6
11.4~16.6

12.8±0.5
AD (9M, 9F)

12.7±0.4

11.1~14.9
12.1±0.8
8.9~15

12.4±0.4

Author Conclusion:

The authors conclude that these data suggest a significant decrease of serum zinc in men with mild cognitive impairment may lead to a decreased Zn-T expression in the brain and subsequent alterations of cellular zinc distributions that may contribute to the progression of AD through increased Aβ processing and deposition.

Funding Source:
Government: NIH
University/Hospital: University of Missouri Columbia, University of Kentucky, Lexington
Not-for-profit
Abercrombie Foundation
Reviewer Comments:
  • Small numbers of subjects in groups
  • There was no information provided about ethnicity, SES, health history, diet, vitamin supplement or medication use in cases or controls
  • No confounding factors were taken into account
  • No exclusion criteria were provided and very few inclusion criteria were provided
  • The author's conclusion was drawn based on previous work of the ZnT-1 in the brain of MCI subjects: Much of the discussion centered around the link between serum levels in the brain from a previous study, rather than focusing on this study and discussing limitations, biases, etc.
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? ???
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? ???
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  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.) No
  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? 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? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? Yes
  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? 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)? No
  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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes