UWL: Association With Outcomes (2009)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • To examine the frequency of major and minor depression in Alzheimer's disease
  • To determine whether these types of depression have a different functional and psychopathological impact
  • To examine whether there is a change in the prevalence of major and minor depression throughout the worsening stages of Alzheimer's disease.
Inclusion Criteria:
  • Meeting criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable Alzheimer's disease
  • No history of closed head injuries with loss of consciousness, strokes or other neurological disorder with involvement of the central nervous system
  • Normal results on laboratory tests to rule out other etiologies of dementia
  • No focal lesions on a magnetic resonance imaging scan
  • A Hachinski Ischemic score less than four.
Exclusion Criteria:

14% of the patients with mild to moderate Alzheimer's disease had to be excluded due to missing data.

Description of Study Protocol:


Consecutive series of 670 outpatients with probable Alzheimer's disease visiting the dementia clinic of a tertiary care center in Buenos Aires between January 1996 and October 2002 for evaluation and treatment of progressive cognitive decline.


Case Series Study 

Blinding used 

A psychiatrist who was blind to the neurological and neuropsychological findings assessed the patients with psychiatric tests, and a neurologist who was blind to the psychiatric ratings completed the neurological examinations.

Intervention (if applicable)

Statistical Analysis

  • Statistical analysis was carried out by using means, standard deviations and ANCOVA with post-hoc planned comparisons (Tukey's test for unequal samples)
  • Frequency distributions were calculated with chi-square tests and Fisher's exact test.


Data Collection Summary:

Timing of Measurements

Series of patients with probable Alzheimer's disease were assessed through the use of several instruments, by both psychiatrist and caregiver.

Dependent Variables

  • Structured Clinical Interview for DSM-IV
  • Cognitive functions assessed through Mini-Mental State Examination
  • Dementia stages assessed through Clinical Dementia Rating
  • Presence and severity of depression assessed through Hamilton Depression Rating Scale
  • Severity of generalized or persistent anxiety assessed through Hamilton Anxiety Rating Scale
  • Apathy assessed through Apathy Scale
  • Irritability assessed through Irritability Scale
  • Delusions assessed through Dementia Psychosis Scale
  • Social supports assessed through Social Ties Checklist
  • Pathological affective crying assessed through Pathological Laughing and Crying Scale
  • Performance of activities of daily living assessed through Functioning Independence Measure 
  • Standardized neuropsychological evaluation: Boston Naming Test, Controlled Oral Word Association Test, Buschke Selective Reminding Test, Digit Span Test and Block Design Test.  

Independent Variables

  • Alzheimer's disease
  • Major and minor depression based on DSM-IV criteria.

Control Variables


Description of Actual Data Sample:

Initial N

670 patients with probable Alzheimer's disease.

Attrition (final N)

670 patients


  • Patients with no depression (N=316): 61% female, mean age 72.3±7.6 years
  • Patients with minor depression (N=177): 65% female, mean age 72.8±7.2 years
  • Patients with major depression (N=177): 59% female, mean age 72.0±8.4 years.


Not mentioned

Other relevant demographics:


There were no significant between-group differences in their main demographic characteristics.


Buenos Aires, Argentina


Summary of Results:


Variables Patients with No Depression (N=316) Patients with Minor Depression (N=177) Patients with Major Depression (N=177) P- value 

Age (years)





Education (years)





Mini-Mental State Examination Score





Dementia Psychosis Scale Score





Hamilton Depression Rating Scale Score





Hamilton Anxiety Rating Scale Score





Functioning Independence Measure Score 

68.6±20.2 63.7±20.6 62.5±19.6 <0.01
Social Ties Checklist Score 5.32±1.9 6.0±1.9 6.31±2.0 <0.0001
Apathy Scale Score 18.9±9.4 22.7±8.3 25.7±8.0 <0.0001
Pathological Laughing and Crying Scale Score (crying subscale score) 2.43±4.2 5.56±5.2 5.52±5.0 <0.0001
Irritability Scale Score 12.8±8.7 15.7±9.5 16.9±9.2 <0.0001
Unified Parkinson's Disease Rating Scale Score 9.39±9.4 17.3±15.6 21.4±16.7 <0.0001
Buschke Selective Reminding Test Score 20.1±17.4 20.1±16.4 17.7±17.3 NS
Boston Naming Test Score 14.3±4.1 13.8±4.1 14.6±3.9 NS
Controlled Oral Word Association Test Score 29.4±10.6 29.2±10.2 26.8±9.5 NS
Digits Forward Score 5.0±1.0 4.8±1.3 4.8±1.0 NS
Digits Backward Score 3.2±1.0 3.1±1.1 3.1±1.0 NS
Block Design Test Score


3.2±2.5 2.9±2.5 NS

Other Findings

26% of the patients had major depression, 26% had minor depression and 48% were not depressed.

Major depression was significantly associated with sad mood in all three stages of the illness, although this association dropped significantly for minor depression in severe Alzheimer's disease.

Both major and minor depression were significantly associated with more severe psychopathology, functional impairments and social dysfunction.

Depressive symptoms that most strongly discriminated between Alzheimer's disease patients with and without sad mood were guilty ideation (84%), suicidal ideation (80%), loss of energy (68%), insomnia (59%), weight loss (59%), psychomotor retardation/agitation (58%), poor concentration (58%), loss of interest (55%), apathy (24%) and irritability (17%). 

Author Conclusion:

In conclusion, our study demonstrates that the DSM-IV criteria for major depression and minor depression identify clinically relevant syndromes of depression in Alzheimer's disease. Future studies should demonstrate the long-term stability and predictive validity of major depression and minor depression in Alzheimer's disease, as well as further explore the relationship of subsyndromal depression and functional impairment.

Funding Source:
University/Hospital: University of Western Australia, Fremantle Hospital Research Foundation
Raine Medical Research Foundation
Other non-profit:
Other: Australian Rotary Health Research Fund
Reviewer Comments:

Authors note the following limitations:

  • 14% of the patients with mild to moderate Alzheimer's disease had to be excluded due to missing data; incomplete evaluations resulted from missing data on the remaining instruments
  • Study group consisted of patients attending a dementia clinic at a tertiary care center, which may have biased the findings towards more severe cases
  • No pathological confirmation of clinical diagnosis of probable Alzheimer's disease
  • Possibility of pseudodementia in some of the Alzheimer's disease patients with dementia.
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? 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? 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.) 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? N/A
  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? 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? 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? 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? 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