EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine whether high dietary copper intake is associated with increased cognitive decline among persons who also consume a diet high in saturated and trans fats.

Inclusion Criteria:

Chicago residents aged 65 years and older who participated in the Chicago Health and Aging Project (CHAP).

Exclusion Criteria:

Initial exclusion criteria not described
Subjects with a potentially invalid FFQ
Subjects who completed the FFQ more than 2.5 years after baseline.

Description of Study Protocol:

Recruitment

Community residents were all participants in the ongoing Chicago Health and Aging Project (CHAP). Recruitment methods were not described.

Design

Community-based prospective cohort study.

Statistical Analysis

Dietary intakes of copper and fats were related to change in global cognitive score (the mean of the four tests)
Z-scores were computed for each test using the means and standard deviations from the baseline study population and averaged these into a single global measure
Mixed effects models were used to estimate risk factor associations with cognitive change
Before the analyses, the best model of the covariates was determined by considering non-linear associations and interactions among covariates.

Data Collection Summary:

Timing of Measurements

Cognitive function assessed at baseline, three years and six years
Food frequency questionnaire completed a median of 1.2 years after baseline.

Dependent Variables

Cognitive function assessed using four cognitive tests administered during in-home interviews:

East Boston Tests of Immediate Memory and Delayed Recall
Mini-Mental State Examination
Symbol Digit Modalities Test.

Independent Variables

Dietary assessment was performed with a modified Harvard food frequency questionnaire.

Control Variables

Energy
Age
Sex
Race
Education
Cognitive activities
Physical activities
Alcohol consumption
Stroke
Heart disease
Hypertension
Diabetes mellitus
Vitamin E in food
Total vitamin C
Niacin in food
Total folate
Saturated fat
Trans fat
Polyunsaturated fat.

Description of Actual Data Sample:

Initial N:

6,158 community residents
4,390 completed at least two cognitive assessments and an FFQ
217 subjects had potentially invalid FFQ
460 completed the FFQ more than 2.5 years after baseline.

Attrition (final N)

3,718 participants included in final analysis.

Age

Aged 65 years and older.

Ethnicity and Anthropometrics

Copper Intake Quintile 1: Mean age 74.5 years, 65.8% female, 69.5% African American
Copper Intake Quintile 2: Mean age 74.8 years, 61.6% female, 62.6% African American
Copper Intake Quintile 3: Mean age 74.3 years, 57.9% female, 59.0% African American
Copper Intake Quintile 4: Mean age 74.0 years, 57.7% female, 62.2% African American
Copper Intake Quintile 5: Mean age 74.0 years, 67.1% female, 48.5% African American.

Location

Chicago, IL.

Summary of Results:

Key Findings

Cognitive scores declined on average by 4.2 standardized units per year
Among persons whose diets were high in saturated and trans fats, higher copper intake was associated with a faster rate of cognitive decline
Overall, dietary intakes of copper, zinc and iron were not associated with cognitive decline after adjustment for multiple confounders
In multiple-adjusted models, the difference in rates for persons in the highest (median, 2.75mg per day) vs. lowest (median, 0.88mg per day) quintiles of total copper intake was -6.14 standardized units per year (P<0.001) or the equivalent of 19 more years of age
There was also a marginally statistically significant association (P=0.07) with the highest quintile of food intake of copper (median, 1.51mg per day) and a strong dose-response association with higher copper dose in vitamin supplements
Copper intake was not associated with cognitive change among persons whose diets were not high in these fats.

Multiple-Adjusted Differences in the Estimated Annual Rate of Change in Cognitive Score Among Persons With and Without High Intake of Saturated and Trans Fats According to Quintile of Copper Intake Among 3,718 Participants in the Chicago Health and Aging Project, 1993 - 2002

Total Copper	Intake Quintile 1	Intake Quintile 2	Intake Quintile 3	Intake Quintile 4	Intake Quintile 5
Median, mg per day	0.88	1.05	1.18	1.38	2.75
Diet High in Saturated and Trans Fat (N=604)
Multiple-adjusted β (P-value)	Referent	-0.24 (0.87)	0.79 (0.63)	-2.95 (0/09)	-6.14 (<0.001)
Diet Not High in Saturated and Trans Fat (N=3,114)
Multiple-adjusted β (P-value)	Referent	0.62 (0.43)	0.36 (0.65)	0.91 (0.24)	0.44 (0.60)

Copper From Food	Intake Quintile 1	Intake Quintile 2	Intake Quintile 3	Intake Quintile 4	Intake Quintile 5
Median, mg per day	0.87	1.02	1.13	1.27	1.51
Diet High in Saturated and Trans-Fat (N=604)
Multiple-adjusted β (P-value)	Referent	-0.13 (0.93)	0.77 (0.62)	-2.03 (0.22)	-3.49 (0.07)
Diet Not High in Saturated and Trans Fat (N=3,114)
Multiple-adjusted β (P-value)	Referent	0.61 (0.43)	0.20 (0.80)	-0.03 90.97)	0.97 (0.22)

Author Conclusion:

These data suggest that a high dietary intake of copper in conjunction with a diet high in saturated and trans fats may be associated with accelerated cognitive decline. The increase in the rate for the high-fat consumers whose total copper intake was in the top 20% (more than 1.6mg per day) was equivalent to 19 more years of age.

Funding Source:

Government:

National Institute on Aging

Reviewer Comments:

Inclusion/exclusion criteria and recruitment were methods were not described
Food frequency data was not collected at the same time for all subjects
Authors note the following limitations:
- Potential for inaccurate measurement of dietary copper, because the copper content of plant foods depends on the soil and varies by region
- Observational study design of CHAP limits causal interpretation
- Associations between high copper intake and both higher education and cognitive activity argue against unrecognized confounding as an explanation.

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?	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?	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?		No
	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?	???
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	No
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