EAL

UWL: Association With Outcomes (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To describe and analyze two modes of weight loss (progressive and severe) in the course of Alzheimer disease (AD).

Inclusion Criteria:

Diagnosis of Alzheimer disease and presence of a caregiver able to ensure the quality of follow-up.

Exclusion Criteria:

Diagnosis of Alzheimer disease more than five years before the study
Activities of Daily Living (ADL) score less than three
Uncontrolled heart failure
Severe or unstable angina
Uncontrolled arterial hypertension
Severe orthostatic hypotension
Severe renal or liver failure
Severe anemia
Vascular disorders
Systemic disease
Clinically relevant hyperthyroidism or hypothyroidism
Clinically relevant vitamin deficiency
Concomitant malignancy
Severe or total blindness or deafness.

Description of Study Protocol:

Recruitment

Participants in the hospitals of Toulouse, France, as part of the Etude Longitudinale de Suivi de la Maladie d'Alzheimer (ELSA) study, which has followed patients with Alzheimer disease since 1994.

Design

Prospective cohort study of patients with Alzheimer disease with evaluation conducted at pre-study, six months and one year. Nutrition, neuropsychology, function and care-giving burden were evaluated.

Statistical Analysis

Two groups of subjects were analyzed: Those who had lost more than 4% of body weight during the first year, and those who had lost more than 5.0kg during the first six months of follow-up
Student's T-tests were used to compare normally distributed quantitative variables across groups
Nonparametric Kruskal-Wallis tests were used when the hypothesis of normality was not met
For qualitative variables, chi square or Fisher's exact tests were performed
Multivariate logistic regression was used to identify the factors independently associated with weight loss.

Data Collection Summary:

Timing of Measurements

Pre-study, six months and one year.

Dependent Variables

Nutrition evaluated with weight, body mass index (BMI), biological variables (albumin, pre-albumin, orosomucoid, C-reactive protein (CRP), prognostic inflammatory and nutritional index (PINI), Mini Nutritional Assessment, and dietitian administered dietary questionnaire
Cognition evaluated with Folstein's Mini-Mental State Examination
Independence evaluated by interviewing family with the use of the ADL scale and Independent Activities of Daily Living (IADL) scale
Mood evaluated by Cornell's depression scale
Behavior evaluated by the Cohen-Mansfield scale.

Independent Variables

Alzheimer disease.

Description of Actual Data Sample:

Initial N: 395 included (271 females, 124 males)
Attrition (final N): 341 were assessed at six months, and 308 were assessed at one year. During that time, 28 refused to participate, 19 died, 12 were lost to follow-up and 16 to other reasons.
Age: Mean age, 75.4 years
Anthropometrics: At six months and one year, participates were evaluated based on progressive weight loss defined as 4% in one year and severe weight loss defined as weight loss of more than 5.0kg
Location: Toulouse, France.

Summary of Results:

Progressive weight loss (4% in one year) was found in 33.4% of subjects at one year.

Variables	Characteristic of Participants with Progressive Weight Loss	P-value
Degree of dementia	More severe	P<0.0001
Cognitive Impairment	More pronounced	P=0.001
IADL Score	Lower	P=0.0029
Hospital admission rate	Higher	P=0.0002
Institution admission rate	Higher	P=0.0016
Cholinesterase inhibitor	Inverse relationship with progressive weight loss	P=0.011

The presence of an intercurrent event, depression, behavioral disorders, living arrangement, food intake and nutritional status at inclusion were not different between patients with progressive weight loss and others
After multivariate analysis, three variables were independently associated with progressive weight loss: Higher initial weight (odds ratio, 1.04), the absence of a specific treatment of AD (odds ratio, 0.33) and more severe AD (odds ratio, one, 5.8, 7.2).

Severe weight loss (more than 5.0kg in six months) was found in 10.2% of subjects at the first six-month follow-up.

Variables	Characteristic of Participants with Severe Weight Loss	P-value
Initial weight	Higher	P=0.0025
Initial BMI	Higher	P<0.0001
Pre-albumin	Lower	Not provided
CRP	Higher	P=0.0172
Functional status	Lower	P=0.05
Educational level	Higher	P=0.045
Hospital admission rate	Higher	P=0.032
Institution admission rate	Higher	P=0.001

The severity of AD, cognitive status, depression and food intake at inclusion were not different between patients with and with out severe weight loss
After multivariate analysis, three variables were independently associated with severe weight loss: Higher initial weight (odds ratio, 1.14), a higher PINI score (odds ratio, 2.4) and the presence of an intercurrent event (odds ratio, 6.8).

Author Conclusion:

More than one third of subjects had progressive weight loss and Alzheimer disease itself seemed to be the most important risk factor since those with severe forms of the disease were more likely to lose weight. Future studies are needed to compare individuals with different patterns of weight loss. A higher initial body weight may confirm a relationship between obesity and cardiovascular risk factors with Alzheimer disease. Cholinesterase inhibitor was a protective factor against progressive weight loss and this needs to be further studied. Severe weight loss was likely due to a concomitant disease and this was shown by the frequency of inflammatory syndrome or inter-current events in these subjects. In conclusion, rigorous, early and regular follow-up of nutritional variables is mandatory in patients with AD because the prognosis of the two modes of weight loss differ and nutritional support is useless if provided too late in severe weight loss.

Funding Source:

Government:

French Ministry of Health

Reviewer Comments:

There was no mention of the use of blinding in this study.

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?	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?	Yes
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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	Yes
	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.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	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?		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?	???
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