Unintended Weight Loss in Older Adults

UWL: Association With Outcomes (2009)


Wang PN, Yang CL, Lin KN, Chen WT, Chwang LC, Liu HC.  Weight loss, nutritional status and physical activity in patients with Alzheimer's Disease: A controlled study. J Neurol. 2004; 251: 314-320. 

PubMed ID: 15015012
Study Design:
Case-control study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To evaluate the nutritional status of patients with Alzheimer's Disease and the influence of eating behavior, dietary intake, physical activities, cognitive performance and depression on body weight.

Inclusion Criteria:
  • Fulfilled the DSM-IV criteria for clinical diagnosis of Alzheimer's Disease
  • Responsible caregiver living at home
  • Control subjects received comprehensive neuropsychological tests to confirm that they did not have dementia.
Exclusion Criteria:

Patients with secondary causes of dementia such as:

  • Vascular dementia
  • Parkinson's disease
  • Hypothyroidism
  • Vitamin B12 deficiency
  • Syphillis.

Subjects with a history of conditions in the recent five years that might affect energy expenditure, such as:

  • Abnormal renal or liver function
  • Abnormal thyroid function
  • Diabetes
  • Carcinoma.
Description of Study Protocol:


All patients consecutively enrolled from the outpatient department of neurology at Taipei Veterans General Hospital. Control subects were recruited from patients visiting the clinic with other diseases or were spouses of the patients with Alzheimer's disease. Recruitment occurred from July 1999 to June 2001.


Case-control study.

Blinding used

Lab tests.


Demographic data, neuropsychological tests, Geriatric Depression Scale, eating behavior questionnaire, dietary and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed. 

Statistical Analysis

Data first analyzed by descriptive statistics. Continuous variables were presented as mean values±standard deviation. Differences in categorical parameters were tested by Chi-square or Fisher's exact test. The differences in anthropometric, physical activity, dietary intake and biochemical indices between the two groups were analyzed by analysis of covariance (ANCOVA), using age as a covariate. Partial correlation test controlling for age was used to evaluate the relationship between cognitive performance, body mass index (BMI) as well as other anthropometric measurements. Difference was considered statistically significant if a two-tailed P value was less than 0.05. Stepwise logistic regression was used to examine the factors associated with the existence of body weight loss. 

Data Collection Summary:

Timing of Measurements

Demographic data, neuropsychological tests, Geriatric Depression Scale, eating behavior questionnaire, diet and physical activity diaries, anthropometric and laboratory measures of nutritional status were assessed and compared between patients with Alzheimer's Disease and control subjects without dementia.

Dependent Variables

  • Body height and weight was measured using a standard scale with height measurement attachmen. For these measurements, subjects wore indoor clothing were not wearing shoes.
  • BMI  
  • Blood pressure, measured with standard sphygmomanometer
  • Biochemical nutritional status, measured by blood cell count, thyroid function, serum albumin, cholesterol, blood urea nitrogen, fasting blood sugar, uric acid and transferrin
  • Anthropometric measurements of nutritional status: mid-arm circumference (MAC) measured at the midpoint between acromion and olecranon processes and triceps skin-fold thickness (TSF) measured with Lange skin-fold calipers
  • Body composition was measured with bioelectrical impedance analysis; body resistance and reactance were measured by a tetrapolar impedance analyse.

Independent Variables

  • Existence of eating problems, including food rejection, swallowing difficulty, chewing problems and appetite change, recorded by questionnaire
  • Dietary intake and physical activity, measured through three-day diet and physical activity diaries for two weekdays and one weekend day. Consumed food was weighed and food composition measured using food composition tables and compared to Recommended Dietary Allowances (RDAs)
  • Protein intake, measured through 24-hour urinary urea nitrogen  
  • Barthel Index was used to evaluated abilities of daily living activities
  • Cognitive function measured through the Chinese version of the Cognitive Abilities Screening Instrument (CASI)
  • Global dementia status measured with the Clinical Dementia Rating (CDR
  • Depression measured through Geriatric Depression Scale Short Form
  • Habits of cigarette smoking and alcohol consumption were recorded

Control Variable



Description of Actual Data Sample:

Initial N: 51 patients with Alzheimer's Disease (43.1% women), 27 control subjects without dementia (44.4% women, 13 spouses of patients, 14 other patients)

Attrition (final N):  As above

Age:  Mean age of subjects with Alzheimer's Disease: 76.2years±7.4 years; mean age of control subjects, 71.2years±6.7years 

Ethnicity: Not mentioned 

Other relevant demographics: See Results section

Anthropometrics: Demographic data showed no significant differences between spouse and non-spouse control subjects

Location: Taipei, Taiwan.


Summary of Results:



Subjects with Alzheimer's Disease (n = 51) Control Subjects without Dementia (n=27) P value
Education, years 9.9±5.2 11.9±3.9 0.126




MMSE-CE 16.3±5.9 28.3±1.5 <0.001
CDR 1.5±0.6 0.0±0.0 <0.001
Weight, kg 53.3±9.0 61.5±8.9 0.002
Height, cm 157.7±8.2 161.3±8.6 0.114





Systolic BP, mmHg 129.1±18.9 133.7±18.9 0.204
Diastolic BP, mmHg 70.7±11.7 79.7±11.8 0.009
Presence of weight loss, n (%) 28 (54.9%) 4 (14.8%) <0.001
Duration of weight loss, years 1.3±1.5 0.9±1.6 0.580
Estimated body weight loss, kg 3.8±2.8 0.8±1.8 0.007
Cigarette Smoking (n / %) 4 (7.8%) 0 0.292
Alcohol Drinking, n (%) 5 (9.8%) 2 (7.4%) 1.000
GDS-S 3.4±2.7 2.6±2.4 0.449
MAC, cm 25.4±3.4 27.6±2.9 0.035
TSF, mm 15.1±7.5 21.0±7.6 0.015
MAMC, cm 20.6±2.5 21.0±2.4 0.647
Body Fat Weight, kg 14.8±4.8 17.8±5.2 0.017
Body Lean Weight, kg 38.5±7.8 43.9±6.9 0.050
Percentage of Body Fat, % 27.9±7.9 28.4±6.7 0.395
Calories, kcal/day 1978±508.6 1920±509.2 0.711
Protein, g/day 80.2±26.0 82.9±26.7 0.658
Carbohydrate, g/day 276.0±68.3 251.7±86.7 0.122
Fat, g/day 65.9±22.7  66.2±22.1 0.760
Calories, kcal/kg/day 38.0±11.1  31.5±7.9 0.009
Protein, kcal/kg/day 1.5±0.6 1.4±0.4 0.255
Carbohydrate, kcal/kg/day 5.3±1.4  4.1±1.3 0.001
Fat, kcal/kg/day 1.3±0.5  1.1±0.4 0.289
Hemoglobulin, g/dL 13.1±1.8 14.0±1.1 0.079
Albumin, g/dL 4.3±0.3 4.5±0.2 0.001
Cholesterol, mg/dL 203.2±34.1 215.2±31.0 0.209
BUN, mg/dL 18.0±6.5 17.8±4.4 0.689
UA, mg/dL 6.4±1.6 6.5±2.0 0.845
Transferrin (mg/dl) 249.1±70.1 263.0±83.6 0.622
Free T4, ng/dL 1.0±0.3 1.0±0.2 0.545
Fasting blood sugar, g/dL 97.0±20.5 102.6±16.2 0.345
UUN. g/24 hours 6.6±4.1 9.0±2.9 0.044

Other Findings

More than half of the subjects with Alzheimer's disease lost body weight, and overall these patients were significantly thinner than the subjects without dementia.

Anthropometric and laboratory measures suggested a poorer nutritional status in the patients with Alzheimer's disease. All anthropometric measures were positively correlated with cognitive performance.

The patients with Alzheimer's disease had fewer daily physical activities, and a higher percentage of refusing food (25.5% vss 0%, P=0.002), poor appetite (29.4% vss 11.1%, P=0.092), or excessive eating (17.6% vs. 0%, P=0.024).

However, daily energy intake was not significantly different between the two groups. The patients with Alzheimer's disease, especially those presenting with body weight loss, consumed more kcal per kg per day.  In the food composition analysis, patients with Alzheimer's disease consumed more carbohydrate than control subjects did.

Multivariate regression analysis showed that the existence of Alzheimer's disease (odds ratio=6.7, 95% CI: 1.8 - 24.5, P=0.004) and poor appetite (odds ratio=5.2, 95% CI: 1.3 - 20.0, P=0.018) were the main risk factors for weight loss.

Author Conclusion:

The main results of our study were:

  1. Patients with Alzheimer's disease had lower body weight and BMI than the subjects without dementia
  2. Amore severe dementia was associated with a lower body weight, BMI and anthropometric measures (MAC, TSF, body fat and lean weight)
  3. Patients with Alzheimer's disease did not consume fewer calories than did normal subjects
  4. The presence of Alzheimer's Disease was a risk factor for weight loss even after other factors were controlled.

In conclusion, poor intake is not the main factor that causes the weight loss in patients with Alzheimer's disease. We suggest that the pathophysiological process in Alzheimer's disease gives rise to the changes of appetite and metabolic state in patients with Alzheimer's disease, and that these changes contribute to the weight loss.

Funding Source:
Government: Grant from Department of Health, Taiwan
Reviewer Comments:

Different numbers of patients and control subjects. Control subjects not matched to patients, Only group means analyzed. Half of the control subjects were spouses of patients, yet authors claim that their daily dietary intakes were not identical. Recall bias is possible in patients with cognitive impairment. Did not consider other factors affecting food intake, such as medications.

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? ???
  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.) 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? N/A
  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.) ???
  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? N/A
  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? N/A
  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? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? Yes
  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? Yes
  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? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  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? ???
  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? 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