UWL: Association With Outcomes (2009)

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

To examine the association of change in BMI with risk of Alzheimer's disease.

Inclusion Criteria:
  • Older Catholic clergy participating in the Religious Orders Study
  • No dementia at baseline.
Exclusion Criteria:
  • Met criteria for dementia (N=81)
  • Did not have at least one valid measurement of both weight and height (N=22)
  • Died before first follow-up evaluation (N=24)
  • Had not been in study long enough to reach first follow-up evaluation (N=40).
Description of Study Protocol:


Participants from the Religious Order Study of aging and Alzheimer's disease in older Catholic clergy. Recruited from 40 groups across the United States between January 1994 through December 2003. Participants agreed to annual clinical evaluations and brain donation at the time of death.


Longitudinal cohort study. 

Blinding Used

Evaluations were performed annually by examiners blinded to previously collected data.

Statistical Analysis

  • Ordinary least-squares regression was used to estimate the annual rate of change in BMI for each person
  • Cox proportional hazards models were used to examine how baseline BMI and the annual rate of change in BMI were associated with the risk of developing Alzheimer's disease during follow-up
  • A complementary set of analyses were conducted using linear mixed-effects models to examine the level of, and change in, BMI with decline in cognitive function.
Data Collection Summary:

Timing of Measurements

Participants completed annual clinical evaluations that included direct measurement of height, weight, cognitive function testing and clinical classification of dementia and Alzheimer's disease. Participants were followed for a mean of 5.5 years and completed an average of 6.6 clinical evaluations per person (range one to 10).

Dependent Variables

  • Clinical diagnosis of Alzheimer's disease, based on clinical criteria for dementia and Alzheimer's disease recommended by the Joint Working Group of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association 
  • Change in cognitive function measured through 20 cognitive performance tests, including the Mini-Mental State Examination.

Independent Variables

Change in BMI based on annual measurements of height and weight.

Control Variables

  • Age
  • Sex
  • Education
  • Chronic conditions
  • Depressive symptoms
  • Physical activity
  • For women, a history of estrogen replacement therapy.
Description of Actual Data Sample:
  • Initial N: 999 enrolled in the study at baseline
  • Attrition (final N): After application of exclusion criteria, 832 participants remained. 820 participants completed at least one follow-up evaluation and are included in the analyses (31% male)
  • Age: Mean 80.2 years for subjects with Alzheimer's disease, 74.0 years for those without.


  • 93% White non-Hispanic for subjects with Alzheimer's disease
  • 88.4% White non-Hispanic for those without Alzheimer's disease. 


United States. 


Summary of Results:

Risk of Incident Alzheimer's Disease Associated with BMI After Excluding Persons who Developed Alzheimer's Disease During the First Four Years of Observation

Alzheimer's Disease Subset Excluded from Analysis

Number of Alzheimer's Disease Participants in Analysis

Baseline BMI, HR (95% CI)

Change in BMI, HR (95% CI)



0.944 (0.908 to 0.981)

0.730 (0.625 to 0.852)
Alzheimer's disease diagnosed, year 1 118 0.936 (0.895 to 0.978) 0.706 (0.580 to 0.860)
Alzheimer's disease diagnosed, years 1 and 2 100 0.933 (0.889 to 0.979) 0.644 (0.526 to 0.790)
Alzheimer's disease diagnosed, years 1, 2 and 3 74 0.941 (0.891 to 0.994) 0.613 (0.469 to 0.800)

Alzheimer's disease diagnosed, years 1, 2, 3 and 4


0.949 (0.891 to 1.010)

0.542 (0.403 to 0.730)

Other Findings

  • During a mean follow-up of 5.5 years, 151 persons developed Alzheimer's disease
  • Those who developed Alzheimer's disease were older and had a lower BMI and cognitive function at baseline (both P<0.001)
  • BMI averaged 27.4 at baseline and declined in about half the participants
  • In a proportional hazards model adjusted for age, sex and education, each one-unit less of BMI at baseline was associated with an approximate 5% increase in the risk of Alzheimer's disease (hazard ratio = 0.944, 95% confidence interval: 0.908 to 0.981), and each one-unit annual decline in BMI (about the 10th percentile) was associated with about a 35% increase in the risk of Alzheimer's disease compared with a person experiencing no change in BMI (about the 50th percentile, hazard ratio = 0.730, 95% confidence interval: 0.625 to 0.852)
  • The results were similar after controlling for chronic diseases and excluding persons who developed Alzheimer's disease during the first four years of observation
  • Random effects models showed that the rate of cognitive decline increased by about 8% for each one-unit less of BMI at baseline and declined an additional 40% per year in persons losing one unit of BMI per year compared with those with no change in BMI.   
Author Conclusion:

Declining BMI is associated with increased risk of incident Alzheimer's disease. Loss of BMI may reflect pathologic processes that contribute to the subsequent development of Alzheimer's disease.

Funding Source:
Government: National Institute on Aging Grants R01 AG15819 and P30 AG10161
Reviewer Comments:

Participants were older Catholic clergy. Recruited over a nine-year period from January 1994 through December 2003. Follow-up per participant ranged from one to 10 years. Authors note that findings are based on a selected cohort that differs in important ways from older persons in the general population in regards to education, socioeconomic status and lifestyle.

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? ???
  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.) No
  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.) 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