FNOA: Antioxidants (2011-2012)

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

To investigate the association between phytoestrogen intake and memory function in elderly men and women from urban and rural sites on Java.

Inclusion Criteria:

Elderly at the study sites were tested after recruitment at the community health centers.

Exclusion Criteria:

No specific exclusion criteria was provided.

Description of Study Protocol:

Recruitment

  • Prior to the study, all village elders and staff at local community health centers or care institutes had been informed of the study and subsequently forwarded this information to potential participants
  • The participants had been asked to bring their caregivers and to arrive at the local health centers on the morning of agreed dates if they were interested in participating in the study
  • None of the elderly approached refused participation after they had been given information about the study by trained research assistants and all signed informed consent forms. 

Design

Cross-sectional study. 

Statistical Analysis

  • Descriptive analyses were done using x2 tests for categorical data or univariate general linear models (ANOVA) to assess differences in food intake and other variables of interest between the sites
  • Non-parametric Spearman's rank correlations were carried out to assess associations between the variables
  • Linear regression analyses were used to predict Hopkins Verbal Learning Test (HVLT), including immediate recall (IR) and delayed recall (DR) scores from phytoestrogen intake and including the following covariates: 
    • Age at the time of testing
    • Sex
    • Years of further education
    • Study site
  • In secondary analysis, intake of other foods were also entered as covariates.
Data Collection Summary:

Timing of Measurements

  • Between April and June 2006 in Jakarta 
  • Between December 2006 and February 2007 in Borobudur and Sumedang. 

Dependent Variables

Memory assessment based on the Hopkins Verbal Learning Test (HVLT), including a total immediate recall (IR) measure and a delayed recall (DR) measure.

Independent Variables

Food frequency questionnaire responses, including intake of tempe or tofu and other genistein-containing foods such as soy milk, intake of rice, fruit (whole as as juice), orange or red vegetables, green vegetables and fish. 

Control Variables

  • Age
  • Sex
  • Education
  • Ethnicity
  • Profession
  • Type of food
  • Mean HVLT score
  • Mean weekly soy intake. 
Description of Actual Data Sample:
  • Initial N: 719
  • Attrition (final N): 719.

Age

Whole Group Jakarta Sumedang Borobudur
69.38±7.85 68.2±7.7 69.1±7.9 71.3±7.9

Ethnicity

  • Jakarta:
    • 47% Javanese
    • 17% Sundanese
    • 36% Other
  • Sumedang: 100% Sundanese
  • Borodudur: 100% Javanese.

Other Relevant Demographics

  Whole Group Jakarta Sumedang Borobudur
Education, %
None 25 13 18 46
Elementary 56 42 80 51
High school 13 28 2 3
Academy/university or higher 7 16 0 0
Profession, %    
None 31 61 14 8
Civil servant 7 11 5 3
Business/trade 13 9 2 14
Army/police 4 5 3 3
Farmer 36 1 69 53
Laborer 8 2 3 19

Location

Jakarta, Sumedang and Borobudur in Java, Indonesia.

 

Summary of Results:

Key Findings

Food Intake and Memory Performance

  • Most participants consumed soy products on a daily basis. The average consumption of either food was nine times a week. Only 5% of the cohort ate no tempe or tofu at all, while 65% of the cohort consumed both soy products once or more than once daily.
  • A strong positive association was seen between the reported weekly intake of tofu and tempe (R=0.85, P<0.001)
  • Too few people consumed soy milk or other soy products, so these data were not included in the analysis
  • The memory performance data were normally distributed and need no transformation prior to analysis
  • There were significant differences in both IR and DR between sites, with participants in Jakarta scoring significantly higher than those in rural areas of Sumedang and Borobudur
  • Participants were overall younger and better educated in Jakarta, which explained the results of the differences in DR performance between the sites (P=0.5)
  •  Ethnicity, socioeconomic status and sex were not related to memory performance in these analysis.

Associations Between Demographics, Food Intake and Isoflavones and Cognitive Function

  • Spearman rank correlations performed on food intake per week showed that age was not associated with the intake of any of the foods, apart from the consumption of fish, which was lower in older people (R=-0.12, P<0.001)
  • Those with higher levels of education were more likely to have a healthier food intake including fruit, vegetables and fish (r=-0.19, P<0.001)
  • A healthy dietary pattern, in turn, was related to better memory performance (R=-0.3, P<0.001 and R=0.48, P<0.001)
  • Tofu had small negative association with memory, but was positively linked with other food intake as was tempe which by itself was not associated with memory performance (R=-0.08, P<0.04)
  • Linear regression analysis indicated that weekly tofu intake had a negative association with memory in analyses controlled for age, sex, education and site
  • Tempe was independently significantly related to better IR memory (with a similar trend for DR) performance
  • The intake of fruit was found to have an independent positive association with both IR and DR.
  HVLT (IR) HVLT (DR)
  Step 1 Step 2 Step 1 Step 2
Tempe ß=0.12, P=-0.05 ß=0.12, P=0.06 ß=0.12, P=0.06 ß=0.11, P=0.09
Tofu ß=-0.18, P=0.005 ß=-0.17, P=0.006  ß=-0.17, P=0.006  ß=-0.17, P=0.008
Fruit - ß=0.14, P<0.001  - ß=0.13, P=0.001
  • Analyses using median splits of soy product intake per week gave similar results to those concerning continuous consumption per week, showing a better memory performance in those who did not consume tofu daily or more than once daily
  • In participants who were 68 years of age or older, tofu was associated with worse IR memory performance, independently of age, education and site
  • Tempe was independently related to better IR memory performance
  • In all participants (regardless of age), fruit consumption was linked with better IR performance. 
  Less than 68 Years of Age >  Years of Age
  Step 1 Step 2
HVLT IR    
Tempe NS NS β=0.22, P=0.02 β=0.25, P=0.009
Tofu NS NS β=0.27, P=0.005 β=0.29, P=0.002
Fruit - β=0.16, P=0.002 - β=0.17, P=0.004
HVLT DR    
Tempe NS NS β=0.15, P=0.12 β=0.16, P=0.11
Tofu β=-0.18, P=0.06 β=-0.13, P=0.16 β=-0.17, P=0.08 β=-0.20, P=0.04
Fruit - β=0.11, P=0.04 - β=0.18, P=0.002

 

Author Conclusion:
  • In this study, the consumption of tofu had negative associations with memory functions. The intake of tempe was related to better memory functions in these analyses. While tempe consumption had no significant associations with memory by itself, it seemed to exert protective effects only when entered in analysis with tofu consumption and could potentially offset some of its negative effects. 
  • When other foods were added, the intake of fruit also showed an independent positive association with better memory performance. When analyses were stratified for age, the results for soy products pertaining to those who were over 68 years of age conform to the initial hypothesis. In conclusion, in this study higher intake of tofu was found to be related to lower memory performance, while tempe may offset this. Future studies should validate this finding and investigate possible mechanisms of action.
Funding Source:
Not-for-profit
Alzheimer's Research Trust
Foundation associated with industry:
Reviewer Comments:

There were differences in the groups studied, as participants from Jakarta were younger and better educated than those in Borobudur and Sumedang. The authors note the following limitations:

  • The sampling methods did not allow for generalization of the results. While the ethnicity of the participants did not relate to memory performance in the current analysis and tempe with memory function were also independent of the study site, unplanned post-hoc analysis stratified for age and site revealed that associations in those over 68 years of age pertained to people from Jakarta with similar trends for the Borobudur site, but not for Sumedang.
  • Possibly different test procedures related to translations and additional variances caused by different testers between the sites could have been responsible for the lack of significant associations of soy products with memory for Sumedang. Post-hoc analyses did show that positive associations between memory performance and intake of fruit among the Sundanese were maintained independently. This could indicate that methodological differences were insufficient to confound the results between sites.
  •  It is plausible that power issues were responsible for the findings of unplanned stratified analyses for age and site. To systematically investigate all interactions or stratification was not possible due to limited numbers of participants per cell. This finding need to be investigated in more detail in future studies with a larger sample size. 
  • Another limitation is related to self-report of food consumption, which many not be a reliable measure of phytoestrogen intake. Intake of foods can be under-reported in cases with memory deficiency; however, caregivers substantiated self-reported data. If this aspect would have played a major role in the this study, one would have expected lower intakes of both soy products to impart higher risk, while for tofu a higher risk was detected. 

 

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? Yes
  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? 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? Yes
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? No
  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? ???
  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.) ???
  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? No
  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.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  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? Yes
  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? Yes
  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? 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