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Keywords:

  • Alzheimer's disease;
  • apathy;
  • depression;
  • diagnosis;
  • elderly

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Background:  A depressive state with Alzheimer's disease (AD) is difficult to differentiate from major depression (MD) in many cases. The purpose of this study was to identify differences between the two disorders using a battery of clinically available psychological tests.

Methods:  We evaluated depression and apathy using the Geriatric Depression Scale consisting of 30 items (GDS30) and Apathy Scale in 38 patients with AD and 31 with MD who were diagnosed based on clinical symptoms and radiological findings. In addition, the Cornel Medical Index (CMI) was employed to compare the psychological features of the two disorders.

Results:  In AD patients, the Apathy Scale score was greater than the GDS30 score, suggesting a strong tendency toward apathy. There was a significant difference in the GDS30/Apathy Scale score ratio between the two groups (P < 0.05, OR: 3.11). When examining the downstream mental items of the CMI, the values of tension-category parameters were significantly greater in AD patients, whereas those of depression-category parameters were significantly higher in MD patients. In individual patients, we compared the scores for the two categories, and there was a marked difference (P < 0.001, OR: 10.6).

Conclusion:  These results suggest that the GDS30, Apathy Scale, and CMI are useful for differentiating MD from AD and evaluating their psychological features.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Alzheimer's disease (AD) causes various psychiatric symptoms in addition to cognitive impairment.1 Depression is one of the most frequent psychiatric symptoms in AD patients.2 Furthermore, apathy is also observed with a depressive state in the presence of AD.3 However, Alzheimer's disease with depression (AD-D) is sometimes difficult to differentiate from senile major depression (MD), despite careful follow up. As therapeutic strategies differ between AD-D and MD, a misdiagnosis might lead to the deterioration of the condition. Briefly, long-term therapy with antidepressants might deteriorate cognitive impairment. Previous studies have proposed a method to evaluate dementia-related depression4 and criteria for AD-D5. However, a simple, useful, clinical examination method to differentiate AD-D from MD should be developed. In the present study, we compared AD-D with senile MD using psychological tests to establish differential diagnosis-based treatment for psychiatric symptoms of AD-D.

SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

The subjects were 69 patients with MD or AD-D aged 65 years or older who were recruited according to the criteria discussed later. All of them had attended the Mental Vitality Clinic (depression outpatient clinic for the elderly) or Memory Clinic (dementia outpatient clinic), National Center for Geriatrics and Gerontology between 1 April 2005 and 31 March 2009 (AD-D: 38 patients, MD: 31 patients). In the present study, diagnoses were made as accurately as possible to compare typical patients.

Criteria for AD-D included the Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSM-IV) criteria, mild dementia (mini-mental state examination (MMSE) score of 18–27), and a GDS30 score of 11 points or more. In addition, we carried out magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) in all patients, and selected patients in whom MRI showed atrophy of the hippocampus and diffuse atrophy of the cerebral cortex, and SPECT showed a reduction in blood flow in the parietal lobe and posterior cingulate gyrus. SPECT is very useful for diagnosing AD.6 We excluded patients meeting the following criteria:

  • 1
    Presence of larger infarcted foci on MRI
  • 2
    Marked aphasia and/or frontal lobe symptoms

Criteria for MD included the DSM-IV criteria, an age of 65 years or older at initial onset recorded on inquiry and a normal or slightly reduced cognitive function (MMSE > 20). We excluded patients meeting the following criteria:

  • 1
    Marked reduction in activities of daily living (ADL) related to hemiplegia or Parkinson's syndrome (Barthel Index: less than 75)
  • 2
    History of alcoholism and/or drug addiction
  • 3
    Symptoms of psychosis such as hallucination and delusion, delirium, dissociated sensory disturbance or suspected personality disorder
  • 4
    Presence of infarcted foci larger than lacunar infarction on MRI
  • 5
    Findings of AD implicated on SPECT

The demographic data are presented in the Table 1.

Table 1.  Demographic data on the subjects
 Major depression (MD)Alzheimer's disease with depression (AD-D)
  1. The data are shown as mean ± SD except for sex. All categories of baseline data had no significance. MMSE, mini-mental state examination.

No. patients3138
Age (years)74.6 ± 5.676.8 ± 5.5
Sex (male/female)7/248/30
Age of onset (years)72.9 ± 5.773.2 ± 8.9
Educational achievement (years)9.1 ± 2.58.9 ± 2.7
Baseline MMSE25.0 ± 4.022.8 ± 3.6
Barthel Index92.3 ± 8.495.2 ± 7.6

Evaluation items

We used the GDS as an index of depression.7 For the assessment of apathy, which is defined as a lack of motivation,8 we used the Apathy Scale (Japanese version). This scale consists of 16 questions, and the full score is 42 points, with a cut-off of 16 points.9 Essentially, this scale has been used to evaluate post-stroke apathy.10 However, it is also useful for evaluating AD-related apathy.2 For detailed psychological examination, we used the Cornel Medical Index (CMI).11 Using this index, a neurotic tendency can be expressed as numerical data based on physical and mental complaints. In the present study, we compared the mental subcategory of the CMI (consisting of six categories: inadequacy, depression, anxiety, sensitivity, anger and tension). All psychological tests were simultaneously carried out by psychologists on the day of initial consultation or second consultation.

Statistical analysis

To compare the mean GDS and Apathy Scale scores and values of the mental sub-category of the CMI, significance was assessed using the Mann–Whitney U-test. To examine differences between the GDS and Apathy Scale scores in individual patients, we used the χ2-test. Similarly, among the mental subcategory of the CMI, we compared the depression score with the tension score in each patient using the χ2-test. P < 0.05 was regarded as significant. For the χ2-test, we calculated the odds ratio (OR).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

When comparing the total GDS30 and Apathy Scale scores between MD and AD-D patients, the total GDS30 score was higher in MD patients, and the total Apathy Scale score was higher in AD-D patients. However, simple comparison did not identify any significant difference (Fig. 1). We compared the proportion of patients in whom the Apathy Scale score was greater than the GDS30 score. In the AD-D group, the proportion of such patients was significantly higher. In the MD group, the proportion of patients in whom the GDS30 score was greater than the Apathy Scale score was significantly higher. The OR was 3.11 (95% confidence interval (CI) of the OR: 1.16 ≤ OR ≤ 8.37) (Fig. 2).

image

Figure 1. Comparison of the Geriatric Depression Scale (GDS) and Apathy Scale scores between major depression (MD) and Alzheimer's disease with depression (AD-D). No significant differences were identified.

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Figure 2. Comparison of the number of patients with respect to differences in the Apathy Scale and Geriatric Depression Scale (GDS) scores. AD-D, Alzheimer's disease with depression; MD, major depression.

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We compared the six categories comprising the downstream mental items of the CMI between the MD and AD-D groups. The scores for depression, anxiety, sensitivity and anger were higher in the MD group; there were significant differences in the scores of depression (z = 2.82, P < 0.05) and sensitivity (z = 2.34, P < 0.05). In the AD-D group, the scores for inadequacy and tension were higher; there was a significant difference in the tension score (z = 2.51, P < 0.05) (Fig. 3). We calculated the scores for tension and depression in each patient, and compared them between the MD and AD-D groups. In the AD-D group, the proportion of patients in whom the tension score was higher than the depression score was significantly larger. In the MD group, the proportion of patients in whom the depression score was higher than the tension score was significantly greater (OR: 10.3, 95% CI: 4.06 ≤ OR ≤ 27.52) (Fig. 4).

image

Figure 3. Cornel Medical Index-based psychological subgroups. AD-D, Alzheimer's disease with depression; MD, major depression.

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image

Figure 4. Comparison of the number of patients with respect to differences in the tension and depression scores among the downstream items of the Cornel Medical Index. AD-D, Alzheimer's disease with depression; MD, major depression.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

Depression has been termed pseudodementia as a result of its dementia-like symptoms, such as a depressive mood and psychomotor inhibition. Recent studies have shown the close association between depression and dementia. The incidence of MCI increases with the severity of depression.12 A study reported that the condition deteriorated to AD in a high proportion of elderly patients with depression during a 4- to 18-year period of follow up.13 According to another study, a neuropsychological test with the MMSE in elderly depressive patients without dementia showed cognitive hypofunction. In particular, the speed of information processing was reduced.14 Also executive abilities were impaired in elderly patients with MD.15 These results suggest that it is difficult to differentiate MD from AD-D. However, appropriate intervention might relieve symptoms or delay disease progression, although treatment methods differ between the two disorders. Therefore, we must make maximum efforts to differentiate these disorders.

Previously, a differentiation method using a biochemical procedure was proposed.16 However, it is still difficult to differentiate a depressive state related to initial AD-D from MD in primary care. To examine the differences between the two disorders, typical patients should be compared. However, it is difficult to accurately diagnose these disorders based on clinical symptoms and the results of simple cognitive function tests alone, as shown in patients with MD-related pseudodementia. In the present study, diagnoses were made as accurately as possible, using radiological examinations as an auxiliary diagnostic procedure. The results of these examinations might be more useful for assessing patients in whom differentiation is difficult.

The present study showed that mood and vitality assessment were important for differentiating MD from a depressive state related to AD-D. Compared with the GDS score, the relatively high Apathy Scale score was characteristic of AD-D. In the AD-D group, apathy was a characteristic finding, which might be one of the important differences from MD. The present results suggest that, even in patients showing a high GDS score, the possibility of AD-D should be considered when the Apathy Scale score is high.

Both the GDS and Apathy Scale can be simply applied in clinical practice. However, based on the results of the present study, the use of a combination of the two scales and comparison of the results might be useful for differentiating AD-D from MD in elderly people. Several methods to evaluate apathy have been proposed.17,18 However, the Apathy Scale (Japanese version) used in the present study is available for elderly patients in whom ADL are relatively well maintained.

In addition, the CMI, which is routinely used although the number of question items is large, is also useful for differentiating the two disorders. AD-D might be characterized by the coexistence of the tendency of tension as well as apathy. This can be interpreted as a kind of reaction for the primary brain hypofunction and psychiatric symptoms responding to it. Clinically, this sign is difficult to differentiate from a depressive state, although it differs from apparent cognitive hypofunction resulting from thought inhibition in the presence of depression. Considering such psychological inhibition, mental approaches and care should be developed. The present study using the GDS, Apathy Scale and CMI showed the psychological differences between AD-D and MD of the elderly, which might facilitate a differential diagnosis.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES

This work was supported by the Research Grant for Longevity Sciences (18C-8) from the Ministry of Health, Labour and Welfare. The protocol of this study was approved by the Ethics Committee, National Center for Geriatrics and Gerontology.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. REFERENCES