FNOA: Antioxidants (2011-2012)

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

To investigate the association between markers of vascular disease and cognition in a community-dwelling non-demented elderly population while adjusting for vascular and non-vascular confounds.

Inclusion Criteria:

Not provided.

Exclusion Criteria:

Not provided.

Description of Study Protocol:

Recruitment

All medically stable, non-demented community-dwelling individuals aged over 65 years who were able to provide consent and cooperation with neuropsychological testing were eligible for recruitment.

Design

Cross-sectional study. 

Statistical Analysis

  • Multiple linear regression models were used to investigate the relationship between vascular biomarkers and neuropsychological tests, controlling for identified covariates
  • The relationship between neuropsychological test scores and vascular biomarkers (homocysteine, C-reactive protein, glycosylated haemoglobin and LDL-cholesterol) were first modelled individually in base models controlling for gender, age, social class and educational status
  • Association between global cognitive performance and potential lifestyle, dietary, psychosocial and clinical confounders were explored in backward regression models
  • In the final analysis, the relationship between neuropsychological test scores and vascular biomarkers were determined using multivariate analysis while adjusting for all significant confounders determined in exploratory analysis.
Data Collection Summary:

Timing of Measurements

2003 to 2005.

Dependent Variables

Neuropsychological test scores including:

  • Mini-mental state examination (MMSE)
  • Pre-morbid IQ (NART)
  • Letter fluency (FAS)
  • Category fluency (Animals)
  • Psychomotor processing speed (WAIS-III digit symbol coding)
  • Working memory (WMS-III letter number sequence)
  • Visual memory (immediate and delayed) (WMS-III-R visual reproduction)
  • Verbal memory (WMS-III serial words)
  • Learn slope
  • Short delay recall
  • Long delay recall
  • Recognition
  • Total recall list one to four
  • List B recall
  • Proactive interference
  • Retroactive interference.

Independent Variables

Homocysteine level. 

Control Variables

  • Demographic characteristics: 
    • Gender
    • Age
    • Education
    • Social class 
  • Clinical characteristics
    • Current smokers
    • Pack-year
    • Teetotalers
    • Hypertension
    • Systolic blood pressure
    • Diastolic blood pressure
    • Diabetes mellitus
    • Cardiovascular disease
    • Stroke
    • Atrial fibrillation
    • Body mass index
    • Psychotropic medications
    • Statins
    • Anti-hypertensives
    • Non-steroidal anti-inflammatories
  • Psychosocial characteristics: 
    • Life satisfaction index
    • Total depression scale
    • Anxiety
    • Depression
    • Dietary and lifestyle
    • Tea
    • Fish
    • Vegetables
    • Fruit
    • Exercise
  • Biochemical characteristics: 
    • Glucose
    • HbA1c
    • Total cholesterol
    • Low-density lipoprotein
    • High-density lipoprotein
    • Triglycerides
    • C-reactive protein. 
Description of Actual Data Sample:
  • Initial N: 1,349
  • Attrition (final N): 466
  • Age: Mean age, 75.45 (SD 6.06)
  • Ethnicity: Caucasian
  • Other relevant demographics: 44.6% male
  • Location: Dublin, Ireland.
Summary of Results:

Key Findings

Homocysteine:

  • Raised homocysteine was consistently associated in base models with poorer function in several domains on neuropsychological testing, specifically, tests assessing visual memory, verbal recall, psychomotor processing speed and a measure of global cognition, the MMSE. This was independent of known confounds.
  • In multivariate models, controlling for other covariates, homocysteine remained consistently associated with visual memory and verbal recall
  • Associations between cognitive and homocysteine levels adjusted for age, gender, education and social class (Model 1) and adjusted for age, gender, education, social class, alcohol, tea intake, depression, life satisfaction, hypertension, use of psychotropic medications, smoking, stroke and fruit intake (Model 2):
  Model 1  Model 2 
 

Standardized beta

P Standardized beta P
Cognitive test  
FAS test -0.010 0.836 0.028 0.620
Animals -0.31 0.504 0.026 0.620
Visual reproduction one -0.127 0.008 -0.117 0.038
Visual reproduction two -0.127 0.008 -0.139 0.012
Letter number sequencing -0.078 0.144 -0.089 0.148
Digit symbol score -0.134 0.006 -0.084 0.121
Verbal intermediate free recall -0.086 0.08 -0.114 0.033
Verbal short delay recall -0.057 0.243 -0.091 0.093
Verbal recognition -0.076 0.129 -0.088

0.119

Verbal list B recall -0.125 0.011 -0.127 0.022
Composite global score -0.105 0.053 -0.082 0.178
MMSE -0.107 0.025 -0.086 0.117

Lifestyle and psychosocial factors:

  • Factors negatively associated with global cognition scores included increased age, lower social class and a history of stoke or depression
  • Factors that correlated positively included education, higher life satisfaction, increased fruit intake, alcohol and tea intake and a history of hypertension. Cigarette smoking also correlated positively with cognition.

 

Author Conclusion:
  • The findings from this study support the findings from other studies that lifestyle and psychosocial factors may be important in determining cognitive performance
  • Factors such as alcohol use, tea intake, depression, life satisfaction, hypertension, smoking, past history of stroke, intake of fruit and use of psychotropic medication were all found to be associated with global cognitive performance
  • These factors may need to be taken into account as potential confounds in future studies investigating cognition.
Funding Source:
University/Hospital: Mercer's Institute for Research on Ageing
Reviewer Comments:
  • The authors note the following limitations:
    • There was a single timed measurement of vascular biomarkers, which lends itself to measurement error
    • This could contribute to an underestimation of the effect of homocysteine on cognitive performance and lack of association found with the other vascular biomarkers
    • Homocysteine samples in this study were from non-fasting subjects. Other studies have found no significant difference between levels of pre- and post-prandial homocysteine when measured in the same subject
    • This sample was urban Caucasian and the findings may not be applicable to rural or other ethnic populations
    • Although the response rate was comparable to other studies, response bias may have reduced the association between vascular biomarkers and cognitive performance
    • Due to the cross-sectional nature of the study, survival bias could not be accounted for and cause and effect could not be established
  • Although, the sample size was 466, the statement was made that, "Due to fatigue or illiteracy some subjects were unable to complete all the neuropsychological tests." Details about this dropout rate were not provided.
  • Inclusion and exclusion criteria were not provided.
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? ???
  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? N/A
  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? N/A
  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? 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.) 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? No
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  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? 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? Yes
  7.7. Were the measurements conducted consistently across groups? N/A
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