UWL: Association With Outcomes (2009)

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

To compare the natural history of weight change from mid to late life in men with and without dementia in late life.

Inclusion Criteria:

Baseline sample consisted of Japanese American men identified from selective service records who were born between 1900 and 1919 and were living on the island of Oahu, Hawaii in 1965.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:


The Honolulu-Asia Aging Study was a 32-year, prospective population-based study of Japanese American men who had been weighed on six occasions between 1965 and 1999 and who had been screened for dementia three times between 1991 and 1999.


Prospective cohort study. 

Statistical Analysis

  • Independent variables associated with weight change were investigated initially by analyzing as dependent variables mean changes in weight from mid to late life (Examinations Three and Four) and in late life (Examinations Four to Six)
  • A random effects model was used to estimate trajectories of weight change from Examination One to Examination Six
  • Other independent variables were entered into the model to investigate confounding or mediating effects
  • The fully adjusted model was then repeated for dementia subtypes and was stratified for baseline age and presence or absence of the APOE ε4 allele to check for effect modification.
Data Collection Summary:

Timing of Measurements

Subjects had been weighed on six occasions between 1965 and 1999 and had been screened for dementia three times between 1991 and 1999.

Dependent Variables

Weight change: Participants were weighed in light clothing according to a standard protocol at all examination points.

Independent Variables

  • Incident dementia
  • Cognitive function was measured in all participants using the 100-point Cognitive Abilities Screening Instrument
  • Dementia evaluation included neuropsychological investigation, proxy interview, neurological examination and neuroimaging
  • Consensus diagnoses were made by the study neurologist and at least two study physicians
  • Dementia diagnosed according to DSM-III-R criteria, probable and possible Alzheimer's disease according to NINCDS-ADRDA criteria and vascular dementia according to California Alzheimer Disease and Treatment Centers criteria.

Control Variables

  • Age at study entry
  • Years of formal education
  • History of stroke obtained through surveillance of hospital records
  • Hypertension
  • Diabetes
  • Smoking
  • Impaired physical function
  • Midlife height and weight
  • Depressive symptoms.
Description of Actual Data Sample:
  • Initial N: 3,734 men at Examination Four. 226 had dementia at Examination Five, 135 with dementia at Examination Six, 850 died and 633 did not participate
  • Attrition (final N): 1,890 men at Examination Six without previous dementia in the analytical sample. 112 with incident dementia, 1,778 without dementia
  • Age: Aged 77 to 98 years at Examination Six
  • Ethnicity: Japanese
  • Location: Hawaii.
Summary of Results:

Differences in the Rate of Weight Change Between Participants With and Without Incident Dementia at Examination Six: A Comparison Between Two Life Stages



Examinations One to Four: Mid to Late Life

Examinations Four to Six: Late Life

All dementia

Model 1 +0.04 (-0.06 to +0.14) -0.36 (-0.53 to -0.19)
  Model 2 +0.04 (-0.06 to +0.14) -0.35 (-0.52 to -0.18)
Alzheimer disease Model 1 -0.01 (-0.13 to +0.10) -0.30 (-0.52 to -0.08)
  Model 2 -0.01 (-0.13 to +0.10) -0.30 (-0.52 to -0.08)
Vascular dementia Model 1 +0.27 (+0.05 to +0.50) -0.60 (-1.07 to -0.13)


Model 2

+0.27 (+0.05 to +0.50)

-0.60 (-1.07 to -0.13)

Other Findings

  • Mean midlife BMI for Examination Six participants was 23.9±2.7kg/m2
  • Groups with and without dementia did not differ with respect to baseline weight or change in weight from mid to late life (first 26 years of follow-up)
  • In the late-life examinations (final six years), mean age- and education-adjusted weight loss was -0.22kg per year (95% confidence interval: -0.26 to -0.18) in participants without dementia
  • Men with incident dementia at the same examination had an additional yearly weight loss of -0.36kg (95% confidence interval: -0.53 to -0.19)
  • This was not changed substantially with adjustment for risk factors for vascular disease or functional impairment and was significant for both Alzheimer disease and vascular dementia subtypes. 
Author Conclusion:

Dementia-associated weight loss begins before the onset of the clinical syndrome and accelerates by the time of diagnosis. The potential impact on prognosis should be considered in the case of elderly persons at risk for dementia.

Funding Source:
Government: NIH, NHLBI
Wellcome Trust
Other non-profit:
Reviewer Comments:

Only Japanese American men were studied. High attrition between Examinations Four and Six. Men were examined on several occasions over a period of up to 34 years. Authors note the following limitations:

  • Bias due to attrition is an important consideration in longitudinal studies
  • Weight change is composed of a constellation of processes
  • Only men were included in the cohort.
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? Yes
  2.2. Were criteria applied equally to all study groups? N/A
  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? 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? 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? 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? 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