UWL: Association With Outcomes (2009)

Study Design:
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Quality Rating:
Research Purpose:

To investigate a possible association between low body weight and regional brain dysfunction.

Inclusion Criteria:

Diagnosis of probable Alzheimer's disease was based on the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

Exclusion Criteria:

Patients with serious complications, including cancer, gastrointestinal disorders, cardiovascular disorders, hyperthyroidism, pulmonary disease and chronic infection.

Description of Study Protocol:


Alzheimer's disease patients were recruited from the Tohoku University Outpatient Clinic for Dementia at the Department of Geriatric Medicine.


Cross-sectional study. 

Statistical Analysis

  • Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region
  • Comparison of age, duration of illness, MMSE score, serum biochemistry and regional brain glucose metabolic ratios between the low BMI group and the normal BMI group was performed using two-tailed T-test 
  • Correlations of the glucose metabolic ratio with BMI were also assessed by Pearson's simple correlation methods
  • Multiple regression analyses were performed to assess the ROI values of each region, gender, patient's age and disease duration as the predictors for BMI.
Data Collection Summary:

Timing of Measurements

One-time measurements. All patients underwent routine general, neurological examination, laboratory tests and neuropsychological tests.

Dependent Variables

Regional blood glucose metabolism measured using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG).

Independent Variables

BMI: Low (less than 21) versus normal (more than 21). 

Control Variables

  • Age
  • Gender
  • Disease duration.
Description of Actual Data Sample:
  • Initial N: 27 patients with probably Alzheimer's disease
  • Attrition (final N): 27 patients, low BMI (less than 21, N=15, five males), normal BMI (more than 21, N=12, three males)
  • Age: Mean age, 69.8 years in low BMI group; 68.9 years in normal BMI group
  • Ethnicity: Japanese
  • Other relevant demographics: Mean duration of dementia was 3.4 years (range, two to 13 years)
  • Anthropometrics: Mean BMI was 20.9±2.2kg/m2 (range 17.1 to 24.9)
  • Location: Japan. 
Summary of Results:

Other Findings

  • In the comparison between low BMI and normal BMI groups, there was no significant difference in the patient's age or MMSE score, although the duration of Alzheimer's disease was significantly longer in the low BMI group than the high BMI group
  • No significant difference was observed in serum biochemistry including total protein, albumin, total cholesterol and triglyceride
  • There was no significant correlation of BMI with patients' age and MMSE scores, although there was a tendency of inverse correlation of BMI with duration of the disease (R=-0.357, P=0.068)
  • In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group (P=0.018), whereas no significant differences were found in all the other brain regions
  • Furthermore, regional glucose metabolism in the anterior cingulate cortex (ACC) had a significant and positive correlation with BMI (R=0.450, P=0.018)
  • After adjustment for age, gender and disease duration, regional glucose metabolism in the anterior cingulate cortex was independently associated with BMI
Author Conclusion:

The present study is the first in vivo to explore correlation of regional brain metabolism with BMI in Alzheimer's disease patients. The result demonstrated that hypometabolism in the anterior cingulate cortex was significantly correlated with BMI, but not in other regions, indicating that the anterior cingulate cortex may be preferentially involved in the modulation of nutritional status. The data shown here may provide a new perspective for elucidating the pathophysiology of body weight loss in Alzheimer's disease patients.

Funding Source:
Other: Not reported
Reviewer Comments:

Small numbers of subjects in groups. Authors note that the mean BMI was considerably lower than the mean BMI of Japanese people aged 60 to 69. Authors note the following limitations:

  • Small sample size of research populations
  • Lack of longitudinal data concerning nutritional status
  • Lack of information on dietary intake and physical activity of the patients.
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? 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.) Yes
  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? N/A
  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%.) N/A
  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? N/A
  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? N/A
  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? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  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? 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? ???
  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? No
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? No
  10.2. Was the study free from apparent conflict of interest? Yes