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Keywords:

  • care giver burden;
  • delusion;
  • DLB;
  • GBS scale;
  • hallucination;
  • MMSE;
  • neuropathology

Abstract

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

Background:  It has been reported that Alzheimer’s disease (AD) patients with Lewy pathology have a shorter time from a given baseline to institutionalization than those with AD alone. Taking the clinical distinction between dementia with Lewy bodies (DLB) and AD into consideration, the previous findings may indicate the possibility that the clinical characteristics of DLB patients have an influence on early institutionalization. This study was carried out to clarify whether there are any differences in the symptoms that required institutionalization between patients with DLB and those with AD.

Methods:  Hospital records and standardized data forms completed at admission to a residential care facility were reviewed to assess the profiles in all cases with autopsy-confirmed diagnoses for correct differential diagnosis. We examined functional, cognitive and symptomatic conditions at admission to a residential care facility of 18 DLB and 35 AD patients whose diagnoses were confirmed by autopsy. The examinations were conducted using the Gottfries-Bråne-Steen (GBS) scale and cognitive tests, and the results were compared between the two groups of patients.

Results:  Hallucinations, impaired wakefulness, disturbance of ADL and emotional disturbance, common clinical features compatible with DLB, were more frequently observed in DLB patients than in AD patients (P < 0.05). Moreover, DLB patients had higher scores on cognitive tests than did AD patients at admission to a residential care facility (P < 0.05).

Conclusion:  The distinctive clinical features at admission to a residential care facility may indicate that the reasons for the necessity of institutionalization are different between DLB and AD, and that the interventions specific to DLB patients and their families would be necessary to prevent or postpone institutionalization.


INTRODUCTION

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

Dementia with Lewy bodies (DLB) is the second most frequent neurodegenerative dementing disorder after Alzheimer’s disease (AD) and comprises approximately 20% of cases determined at autopsy. These two major dementing disorders (AD and DLB) account for approximately 60% of total dementing disorders.1,2 DLB is clinically characterized by progressive dementia, which is frequently accompanied by fluctuating cognitive impairment, parkinsonism and psychiatric symptoms including visual hallucination. These cognitive and behavioral features of DLB often make the clinical management of the patients difficult.1 Moreover, many clinicopathological studies have revealed the clinical distinction between DLB and AD. Extrapyramidal signs (EPS) and episodes of confusion, depression, delusion, hallucination and diurnal hypersomnia have been shown to be more frequent in DLB patients than in AD patients.3,4

According to a prospective study, AD patients with Lewy pathology have a shorter time from a given baseline to institutionalization than those with AD alone.3 Taking the clinical distinction between DLB and AD into consideration, the previous findings may indicate the possibility that the clinical characteristics of DLB patients have an influence on early institutionalization, and some studies support this possibility; EPS, depression and delusion, which are clinical features included in the consensus guideline of DLB,1 have been reported to be risk factors for early institutionalization of demented patients.5–8 However, most previous study authors have investigated the risk factors for institutionalization in demented patients without differential diagnoses,5,9,10 and it remains unclear whether each dementing disorder has specific clinical reasons for requiring transition to residential care. To our knowledge few reports are available on institutionalization in DLB patients.

In the current study, we examined functional, cognitive and symptomatic conditions of autopsy-confirmed DLB and AD patients at admission to a residential a care facility and compared the results based on a hypothesis that the conditions for the necessity of institutionalization are different between DLB and AD patients.

MATERIALS AND METHODS

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

Subjects

Cases of neuropathologically diagnosed patients with DLB or AD were reviewed from the files of the Fukushimura Hospital Brain Bank and constituted a consecutive series of cases for which adequate clinical information was available for retrospective study. The DLB cases were neuropathologically selected among neocortical and limbic types based on the consensus guideline of DLB.1,11 The pathological diagnosis of AD was carried out in accordance with the National Institute on Aging-Reagan Institute (NIA-RI) criteria.12 DLB cases with concurrent AD pathology, which fulfilled the pathological criteria for AD,12,13 were excluded because the presence of AD pathology in DLB modifies clinical presentation.14 The cases were also reviewed to exclude those that had infarcts or other neuropathology. Consent for autopsy and research usage of clinical records was obtained from the families of the patients. This study was approved by the ethics committee of the Choju Medical Institute, Fukushimura Hospital.

Study design

Hospital records, consulting physicians’ notes, and standardized data forms at admission to residential care facilities were reviewed to assess the profiles in all cases. Functional, cognitive and symptomatic conditions were evaluated by means of assessment scales for each domain at admission or within a month before admission. Age, sex and experience of hallucinations/delusions were also investigated at admission to a residential care facility.

Measurements

We reviewed neuropsychological tests administered to patients at admission to a residential care facility in Fukushimura Hospital, consisting of the Mini-Mental State Examination (MMSE),15 and the assessment by Hasegawa’s dementia scale (HDS)16 or the HDS revised version (HDS-R),17 which is a neuropsychological test widely utilized in Japan. At the same time, we reviewed the assessment of patients according to the Gottfries-Bråne-Steen (GBS) scale as well.18 This scale measures the degree of dementia and provides profiles of dementia syndromes, and is divided into four subscales measuring motor, intellectual and emotional functions and different symptoms characteristic of dementia. For each question, scores from 0 to 6 were recorded according to the condition of the patient. Items including agony, absentmindedness and distractability were excluded from the comparison because these scores were not available in some cases.

Statistical analysis

Demographic characteristics, cognitive functional tests and the presence of psychiatric symptoms were compared between AD and DLB patients by unpaired T-test or χ2 test. Patients’ scores on the subscales of the GBS were compared using the non-parametric Mann–Whitney U-test test to demonstrate significant differences between AD and DLB patients. Significance was accepted at the 5% level. All statistical analyses were performed using StatView software (version 5.0) for Windows.

RESULTS

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

We identified 18 DLB patients (DLB group) and 35 AD patients (AD group) for whom we had complete GBS scale data dating to their admission to residential care facilities. No significant differences were found between the two groups with regard to sex or age at institutionalization. Cognitive scores were higher in the DLB group at admission than in the AD group (unpaired T-test, MMSE, P = 0.021; HDS, P = 0.216; HDS-R, P = 0.021; see Table 1). But MMSE scores were not available for all cases because of retrospective investigation. Hallucinations were significantly more frequent in the DLB group than in the AD group (χ2 test, P = 0.021; see Table 1). Delusion was more frequent in the DLB group than in the AD group, but approximately 50% of the AD patients also suffered from delusion at admission (see Table 1).

Table 1.  Demographic characteristics, cognitive and psychological conditions at institutionalization
 AD (n = 35)DLB (n = 18)P-value
  • *

    P < 0.05 by unpaired t-test,

  • **

    P < 0.05 by χ2 test.

  • AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; HDS, Hasegawa’s dementia scale; HDS-R, HDS revised version; MMSE, Mini-Mental State Examination.

Female/male23/12 8/100.115
Age at admission78.6 ± 5.476.7 ± 9.90.477
HDS (n) 7.1 ± 5.4 (11)11.5 ± 8.8 (7)0.216
HDS-R (n) 4.3 ± 3.8 (24)10.3 ± 7.1 (11)0.021*
MMSE (n) 6.2 ± 6.1 (14)13.0 ± 5.0 (7)0.021*
Hallucinations; n (%)13 (37)13 (72)0.021**
Delusions; n (%)17 (49)12 (67)0.254

The GBS scale scores are presented in Table 2. In terms of motor functions, scores were significantly higher in the DLB group for motor insufficiency in undressing and dressing, and deficiency of spontaneous activity (Mann–Whitney test, P = 0.046, P = 0.046). In terms of intellectual functions, impaired wakefulness had significantly higher scores in the DLB group than in the AD group (Mann–Whitney test, P = 0.016). In terms of emotional functions, emotional blunting and total emotional function scores were significantly higher in the DLB group than in the AD group (Mann–Whitney test, P = 0.018, 0.025). In terms of differential symptoms common in dementia, no significant difference between the two groups was found.

Table 2.  GBS scale scores of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients at institutionalization
 AD (n = 35)DLB (n = 18)P-value
  1. *P < 0.05 by Mann–Whitney test.

Motor functions
 Total12.4 ± 10.818.0 ± 10.80.062
 Motor insufficiency in undressing and dressing2.62 ± 2.223.88 ± 1.710.046*
 Motor insufficiency in taking food1.54 ± 2.182.66 ± 2.300.056
 Impaired physical activity0.91 ± 1.861.55 ± 2.250.054
 Deficiency of spontaneous activity1.91 ± 1.722.94 ± 1.830.046*
 Motor insufficiency in managing personal hygiene2.94 ± 2.363.66 ± 2.220.379
 Inability to control bladder and bowel2.54 ± 2.513.33 ± 2.110.169
Intellectual functions
 Total28.7 ± 10.530.1 ± 12.10.792
 Impaired orientation in space3.68 ± 1.643.44 ± 1.540.551
 Impaired orientation in time4.74 ± 1.464.38 ± 1.680.449
 Impaired personal orientation2.02 ± 1.502.16 ± 1.650.876
 Impaired recent memory4.34 ± 1.673.66 ± 1.810.210
 Impaired distant memory3.22 ± 1.433.05 ± 1.790.773
 Impaired wakefulness1.45 ± 1.822.88 ± 2.240.016*
 Impaired concentration3.17 ± 1.743.38 ± 1.370.611
 Inability to increase tempo2.80 ± 1.923.50 ± 1.580.173
 Long-windedness3.25 ± 1.663.66 ± 1.320.387
Emotional functions
 Total6.80 ± 3.999.33 ± 3.770.018*
 Emotional blunting2.28 ± 1.743.33 ± 1.640.025*
 Emotional lability1.68 ± 1.492.27 ± 1.900.310
 Reduced motivation2.82 ± 1.673.72 ± 1.700.059
Differential symptoms common in dementia
 Total8.97 ± 6.7510.1 ± 4.920.221
 Confusion2.82 ± 1.862.88 ± 1.450.687
 Irritability1.37 ± 1.591.94 ± 1.430.124
 Anxiety1.28 ± 1.701.44 ± 1.330.414
 Reduced mood1.28 ± 1.721.72 ± 1.740.269
 Restlessness2.22 ± 1.982.11 ± 1.560.954

DISCUSSION

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

Most studies regarding the institutionalization of demented patients have not reported on differential diagnoses. Few reports are available on institutionalization specific to each dementing disorder with a correct diagnosis. To our knowledge, only Lopez et al. carried out a survey on institutionalization based on pathological diagnosis, and in their study they prospectively showed that AD patients with Lewy pathology had a shorter time from a given baseline to institutionalization than those with AD alone.3 However, they did not investigate the conditions of demented patients at the time when residential care was needed. In the present study, we have revealed that functional, cognitive and symptomatic conditions at admission to residential care were different between DLB and AD patients. Thus our results can be considered a first attempt to reveal the possibility that DLB patients and AD patients exhibit different symptoms at the time that it is determined that they require institutionalization, including consideration of autopsy-confirmed diagnoses for correct differential diagnosis.

Preserved cognitive scores in the DLB patients at admission would indicate early transition to a residential care facility as Lopez et al. reported. On the other hand, the significantly frequent hallucinations at admission, despite relatively preserved cognitive scores in the DLB patients, may explain the early institutionalization (Table 1). Interestingly, it has been reported that the risk factors of institutionalization for patients with Parkinson’s disease (PD) are dementia, impairment of activities of daily living and hallucination.19,20 The presence of hallucinations was the strongest predictor for institutionalization in PD patients. Because it has been lately revealed that most cases of PD with dementia neuropathologically fulfilled the criteria of DLB,21 our result of highly presented hallucination (DLB: 72%) may be compatible with previous reports. Both the DLB and AD patients have frequent symptoms of delusions (DLB: 67%; AD: 49%), which are in agreement with a report that delusion is a risk factor of institutionalization.8

Impairment of ADL, impaired wakefulness and emotional disturbance were indeed more frequent at admission to a residential care facility in the DLB patients than in the AD patients as rated by the GBS scale (Table 2). Observed EPS, which consisted of motor insufficiency in undressing and dressing, deficiency of spontaneous activity, motor insufficiency in taking food and impaired physical activity, would presumably have caused the impairment of ADL, although the latter two symptoms were not significantly frequent in DLB patients. Both the DLB and AD patients had high scores in terms of inability to control bladder and bowel movement, which might be a common functional factor that would require residential care. In terms of intellectual functions, no significant difference was found between the DLB and AD patients, except for impaired wakefulness, despite relatively preserved scores on cognitive tests in the DLB patients. Because both of the groups of patients were in advanced stages of dementia with orientation and memory severely impaired, a bottom effect in comparing low cognitive scores might have made the statistical results difficult to interpret. DLB patients had significantly higher scores in impaired wakefulness than did the AD patients. This result is compatible with a core feature of the clinical guideline of DLB, that is, fluctuating cognition with pronounced variations in attention and alertness.1 In terms of emotional functions, DLB patients had significantly higher scores in emotional blunting and total emotional functions than did AD patients. These results may indicate an effect of depressive symptoms, which are also supportive features in the clinical guidelines for DLB.11 In terms of differential symptoms common in dementia, no significant difference was found between DLB and AD patients. The results of the GBS scale showed that motor and emotional functions, which are suggestive of the clinical characteristic of DLB, were more strongly impaired at admission in the DLB patients than in the AD patients, and this may indicate that those symptoms are related to patients’ institutionalization at a stage when their cognitive functions were relatively spared.

When DLB patients have psychotic symptoms, they may receive antipsychotic medication to improve the psychiatric symptoms. Use of standard neuroleptics, however, often induces severe adverse effects including parkinsonism, thus careful attention needs to be paid to neuroleptic drug sensitivity, a supportive feature of the DLB guidelines. On the other hand, antiparkinsonian medications including selegeline, amantadine and dopamine agonists sometimes induce or exacerbate confusion and psychosis (visual illusions, hallucinations and delusions). Therefore, it is difficult to independently identify clinical symptoms of DLB patients who are already on medication.22 Pharmacotherapeutic interventions that prioritize and target those symptoms that may be related to the increased risk of institutionalization of DLB patients are needed.22 From a clinical point of view, it would be useful in deciding the priority of treatments to clarify the risk factors of institutionalization of DLB patients. It has been acknowledged that the use of cholinesterase inhibitors for DLB patients also improves psychiatric symptoms such as hallucination and delusion.22 Because the reduction of the neocortical and hippocampal presynaptic cholinergic inputs is more severe in DLB brains than in AD brains, cholinesterase inhibitors are thought to be more effective in DLB patients than in AD patients.23,24 There is an interesting report showing that the use of cholinesterase inhibitors was associated with delayed nursing home placement in AD patients,25 which suggests that appropriate pharmacological interventions may be expected to prevent or postpone institutionalization in DLB patients more successfully than in AD patients. Further investigations controlling medications with a prospective design and pathological confirmation would be necessary to clarify this issue.

Zarit et al. described family caregivers of patients with dementia as the hidden victims of dementia and pointed out the importance of understanding their burden.26 Impaired ADL, psychiatric symptoms and emotional disturbance of patients with dementia all increase the caregivers’ burden, which is significantly associated with the risk factor of institutionalization.26–28 Thus, the intervention directed toward caregivers is indeed important, and some studies showed that the interventions, which consist of education, support and counseling of caregivers, delay nursing home placement of AD patients.29,30 Taking the clinical distinction between DLB and AD into consideration, interventions specific to caregivers who have DLB patients may also be needed.

REFERENCES

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