EAL

Scheduled Maintenance: Saturday, May 4th, starting at 8PM EST
We will be upgrading some systems and expect the maintenance to last no more than 2 hours. During the maintenance window, you will not have access to this portal.

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate plasma concentrations of the natural tocopherols and the tocopherol oxidation markers α-tocopherylquinone (αTQ) and 5-nitro-gamma-tocopherol (5NGT) in relation to cognitive function in the elderly.

Inclusion Criteria:

Persons over age 65 years residing in the Italian municipality of Conselice.

Exclusion Criteria:

Subjects affected by major sensory-motor deficits or any psychiatric condition other than dementia deemed to hamper a reliable cognitive assessment, and for whom it could not be ascertained whether there had actually been a decline from a previous higher level of functioning, were diagnosed as cognitively unclassifiable and excluded from the present analysis.

Description of Study Protocol:

Recruitment

The data are from the Conselice Study of Brain Ageing (CSBA), a population-based study of elderly Italian persons that aimed to investigate epidemiology and risk factors for cognitive impairment
In 1999 and 2000, 1,016 (75%) of the 1,353 persons over age 65 years residing in the Italian municipality of Conselice participated in the study, with follow-up assessment in 2003 and 2004
Recruitment methods not described.

Design

Prospective cohort study

Blinding used

Not applicable

Intervention

Not applicable

Statistical Analysis

Variables are presented as means ± standard deviations for continuous variables or as number and percentage for categorical variables
Differences among participants stratified by baseline cognitive status and those among cognitively normal subjects stratified into three groups according to their MMSE score were evaluated by analysis of variance or the chi-square test
Correlations between selected continuous variables were studied by using Pearson correlation coefficient
Logistic regression was using to estimate odds ratios and 95% confidence intervals for cognitive status at baseline across tertiles of plasma tocopherols and their derivatives
Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for incident dementia across plasma concentrations of tocopherols and their derivatives
P value for linear trend was calculated for both logistic and Cox models to verify whether there was a linear dose-related association between risk of mild cognitive impairment or dementia and tertiles of vitamin E metabolites
Statistical significance of individual odds ratios and hazard ratios across tertiles was used to detect nonlinear patterns of association.

Data Collection Summary:

Timing of Measurements

Baseline plasma tocopherols and their oxidation markers were measured in subjects assessed in 1999-2000 for mild cognitive impairment (MCI) and dementia
In 2003-2004, information about cognitive status was collected for 615 of the 666 subjects without baseline cognitive impairment.

Dependent Variables

Risk of cognitive impairment identified through cognitive screening and extensive clinical assessment
- Standardized personal interview for collection of data on sociodemographic characteristics, lifestyle, and medical history
- Functional status assessed through basic and instrumental activities of daily living
- Evaluation of depressive symptoms through the Geriatric Depression Scale
- Italian version of the Mini-Mental State Examination
- Standardized medical and neurologic examination
- Routine biochemical blood and urine analysis along with genotyping for APOE ε4 allele
- Mental Deterioration Battery.

Independent Variables

Plasma tocopherols and oxidation markers were analyzed as plasma absolute values divided by serum total cholesterol (since lipids affect their blood availability) after an overnight fast and assessed through standard laboratory methods.

Control Variables

Age
Sex
Education
APOE genotype
Smoking habit
Sedentariness
BMI
Mediterranean diet score
History of cardiovascular disease (i.e. myocardial infarction, angina, peripheral vascular disease and congestive heart failure) and stroke.

Description of Actual Data Sample:

Initial N: 1,016 elderly subjects in original cohort
Attrition (final N):
- Of 761 survivors (54.7% women), 666 did not have baseline cognitive impairment
- Cognitive status information collected for 615 elderly subjects in 2003 and 2004
- 152 subjects had died and 103 had refused to undergo the second examination
Age: Mean age 74.6±6.9 years
Ethnicity: Not reported
Other relevant demographics:
Anthropometrics: Mean BMI 28.4±4.6kg/m²
Location: Italy.

Summary of Results:

Key Findings

During an average of 3.8±0.9 years, 73 incident dementia cases occurred in the cohort at risk
Incident dementia cases were more likely to be older (P<0.001), female (P=0.009), less educated (P<0.001) and sedentary (P=0.033) and to have lower MMSE and Mediterranean diet scores
Compared with the corresponding lowest tertile, the risk of prevalent dementia was higher for the highest tertile of δ-tocopherol divided by cholesterol (odds ratio=3.87, 95% confidence interval: 1.46, 10.27) and α-tocopherol divided by cholesterol (odds ratio=4.02, 95% confidence interval: 1.45, 11.14), but the risk of incident dementia was not directly associated with plasma vitamin E metabolites.
A U-shaped association, with lower risk for intermediate tertiles, was found for prevalent mild cognitive impairment with 5NGT divided by cholesterol, (odds ratio=0.39, 95% confidence interval: 0.17, 0.91) and for incident dementia with gamma-tocopherol divided by cholesterol (hazard ratio=0.42, 95% confidence interval: 0.22, 0.84)
In all multivariate-adjusted Cox models, Mediterranean diet scores remained consistently associated with incident dementia independent of all the other study variables, with an average 16% reduction in dementia risk for every one-point increase (P<0.05).

Author Conclusion:

In conclusion, the present study shows that, in the elderly, both prevalent and incident cognitive impairments are associated with variations in blood concentrations of non-α-tocopherol forms of vitamin E. This finding supports the hypothesis that dietary interventions aimed at modifying plasma vitamin E status may affect the risk of cognitive impairment in older persons. It also prompts further longitudinal investigations and clinical trials in an area, where, up to now, research has been focusing almost solely on α-tocopherol.

Funding Source:

Government:

Italian Ministry of University and Scientific Research

Not-for-profit

Gift from Kenneth Hensley (Oklahoma Medical Research Foundation)

Other non-profit:

In-Kind support reported by Industry:

Yes

Reviewer Comments:

Population-based cohort, large number of confounding variables taken into account. Authors note the following limitations:

Vitamin E dietary intake was not measured, and only semiquantitative dietary data were available
Variables of interest were measured only once and were assumed to be stable during the years of follow-up
Due to the small number of dementia cases, no specific analyses could be performed
Antioxidants work as a system and are affected by many other nutrients
Findings may not apply to a population with different dietary habits or sociocultural background
Significant results were only found after adjustment for serum cholesterol concentrations, and, in addition to a lower dietary intake, unmeasured confounders related to a reduced endogenous synthesis may be relevant to explain the lower cholesterol of participants with dementia.

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?	???
	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?	???
	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?		???
	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?	???
	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)?	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