UWL: Association With Outcomes (2009)
Johnson DK, Wilkins CH, Morris JC. Accelerated weight loss may precede diagnosis in Alzheimer disease. Arch Neurol. 2006; 63(9): 1,312-1,317.PubMed ID: 16966511
To determine the interval between the occurrence of weight loss and the onset of dementia of the Alzheimer type and to characterize the rate of weight change over time in older (aged 65 to 95 years) adults with and without dementia.
- Multiple diagnoses were allowed for the participants with dementia, but dementia of the Alzheimer type was the primary diagnosis
- Participants reporting depressive symptoms but not meeting the criteria for major depression were included.
People with other potentially disorders causing dementia such as Parkinson's disease were excluded.
Archival data from all available research participants without dementia and with weight measurements who were enrolled in a longitudinal study of memory and aging between January 1, 1991 and March 1, 2005.
Retrospective cohort study.
- Group comparisons of quantitative measures at enrollment and at last assessment were conducted using T-tests
- The chi-square test of independence was used for nominal variables
- Piecewise linear regression and random effects models were used to test longitudinal rates of weight change between the groups
- In a second set of analyses, the mediating effects of variables that may affect declining body weight as a function of dementia status were controlled for.
Timing of Measurements
Subjects were followed up for an average of six years. At enrollment and annual follow-up, experienced clinicians assessed each participant for the presence and severity of dementia and body weight.
Rate of weight change: Participants were weighed on medical scales with light clothing.
- Development of dementia of the Alzheimer type was assessed using the Clinical Dementia Rating (CDR)
- Embedded in the clinical evaluation were standard cognitive screening tools, such as the Short Blessed Test for cognitive impairment and the Mini-Mental State Examination.
- Presence of medical disorders
- Physical health
- Socioeconomic status
- Presence of apolipoprotein ε4 alleles.
- Initial N: 449 individuals initially without dementia
- Attrition (final N): 449 individuals; 125 developed dementia (60 males, 65 females)
- Age: Mean age at enrollment was 74.6±9.3 years for those who developed dementia, 79.2±8.2 for those who did not
- Ethnicity: 23 were African American, the remainder were Caucasian
- Anthropometrics: The two groups were similar with respect to the proportion of men and women, educational level and socioeconomic status
- Location: Alzheimer's Disease Research Center, Washington University School of Medicine, St.Louis, Missouri.
- The group that developed dementia of the Alzheimer type was older (4.6 years) and weighed less (8.2 pounds) at study enrollment compared with those who remained without dementia
- The two groups differed on the two cognitive screening measures at the last assessment (P<0.001 for both)
- The participants with dementia of the Alzheimer type were more likely to be widowed (P<0.05), were in poorer physical health (P<0.001), reported more depressive symptoms (P<0.001) and were more likely to take cholinesterase inhibitor and N-methyl-D-aspartate agonist drugs (P<0.001)
- The groups with and without dementia did not differ significantly at last assessment in terms of any of the other medical conditions or medications
- Participants without dementia lost about 0.6 pounds per year
- For those individuals who developed dementia of the Alzheimer type, about one year before the detection of dementia, the rate of weight loss doubled (1.2 pounds per year)
- As a group, participants who eventually developed dementia of the Alzheimer type weighed less (about eight pounds) at study enrollment (when they did not have dementia) than participants who remained without dementia.
Aging with and without dementia of the Alzheimer type is associated with weight loss; however, weight loss may accelerate before the diagnosis of dementia. Specific factors contributing to weight loss are unknown, but these data suggest they operate before the development of dementia of the Alzheimer type. Hence, weight loss may be a preclinical indicator of Alzheimer disease.
|Government:||National Institute on Aging grants P01 AG03991 and P50 AG05681|
Recruitment and inclusion/exclusion criteria not well delineated; multiple medical diagnoses were allowed for the participants with dementia. Authors note the following limitations:
- Individuals were not observed from midlife
- It is possible that heavier individuals lose weight faster than lighter individuals
- Some of the group without dementia may actually contain individuals who have preclinical dementia of the Alzheimer type
- Too few participants were treated with cholinesterase drugs, precluding the analysis of the effect that these drugs may have on weight loss in dementia.
Quality Criteria Checklist: Primary Research
|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|
|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?||???|
|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?||???|
|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.)||???|
|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?||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?||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?||N/A|
|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)?||No|
|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|