Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients

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1 Blackwell Science, LtdOxford, UKPCNPsychiatry and Clinical Neurosciences Blackwell Publishing Pty Ltd Original ArticleDementia and mild AlzheimersJ. Shimabukuro et al. Psychiatry and Clinical Neurosciences (2005), 59, Regular Article Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients JIN SHIMABUKURO, md, 1 SHUICHI AWATA, md, phd 2 AND HIROO MATSUOKA, md, phd 2 1 Department of Psychiatry, Tohoku University Hospital and 2 Department of Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan Abstract In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimer s disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms. Key words Alzheimer s disease, Behavioral and Psychological Symptoms of Dementia, Clinical Dementia Rating, mild dementia, Neuropsychiatric Inventory. INTRODUCTION The Behavioral and Psychological Symptoms of Dementia (BPSD) 1 can significantly aggravate caregiver s distress and can be the major reason for the institutionalization of patients with Alzheimer s disease (AD). 2,3 However, adequate intervention can ameliorate the symptoms of BPSD 4 and improve the quality of life for both the patient and the caregiver. Correspondence address: Jin Shimabukuro, Department of Psychiatry, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai , Japan. cocoa-thk@umin.ac.jp Received 29 July 2004; revised 20 December 2004; accepted 25 December Thus, it is very important to develop a practical and effective strategy for the early intervention of the symptoms of BPSD in mild dementia, which may contribute to keeping the long-term patient s and caregiver s life from an undesirable stressful burden. In studies on the elderly population utilizing a community mental health consulting program, Awata 5,6 showed that patients with mild dementia had delusion, anxiety, depression, irritability or aggression as frequently as those with moderate or severe dementia, and proposed an integrated community care system for the elderly with mild dementia to address these symptoms. In the present study, we examined the characteristics of the BPSD in patients with mild AD who attended the psychiatric ward in a general hospital for

2 Dementia and mild Alzheimers 275 the first time, in order to clarify the target symptoms for early intervention in the community and clinical settings. METHODS The study subjects consisted of 74 patients with AD (male/female: 20/54; mean age ± SD: 76.0 ± 7.9; range: 53-93) and their caregivers who attended the Department of Psychiatry, Furukawa City Hospital for the first time, from April 2001 to July Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, 7 on the basis of complete medical history, comprehensive psychiatric, neurological, and physical examination, laboratory findings of blood, and findings in magnetic resonance imaging and single photon emission computed tomography. In the comprehensive psychiatric assessment, we evaluated the level of cognitive impairment by the Mini Mental State Examination (MMSE) 8 and severities of dementia by the Clinical Dementia Rating (CDR). 9 BPSD was evaluated by the Japanese version of the Neuropsychiatric Inventory (NPI) 10 originally developed by Cummings et al. 11 The NPI can evaluate a wider range of psychopathology, distinguish among different etiologies of dementia, differentiate behavioral changes, and minimize administration time. First, we examined 10 behavioral abnormalities (delusions, hallucinations, dysphoria, anxiety, agitation, euphoria, disinhibition, irritability, apathy, and aberrant motor activity) by calculating the numbers of positive responses to screening questions in each behavioral domain. Second, on the basis of scoring the frequency (1 through 4) and the severity (1 through 3) of each behavioral abnormality, a composite score for each domain was determined as the product of the frequency and severity subscores (maximum, 12). The total NPI score was calculated by adding all composite scores for each NPI domain. Thus, the total NPI score ranged between 0 and 120. Information regarding the NPI was obtained from caregivers who were directly caring for their demented family member. Group comparison of demographic variables, cognitive function, total NPI score and prevalence of 10 behaviors in NPI were performed using one-way anova, c 2 tests and Kruskal Wallis test, respectively. Correlation between the composite scores of each behavioral domain of NPI and the level of the CDR severity was analyzed using Spearman s correlation coefficient. Comparison between the mild AD groups and the moderate or severe AD groups were performed using c 2 tests and the Mann Whitney U-test. RESULTS Table 1 shows the subject s number, mean age, sex ratio, and the mean scores of MMSE in each CDR group. There was no significant difference in mean age and sex ratio between the CDR groups, although the score of MMSE was significantly decreased as the level of severity was increased (F = 96.7, P < 0.01). In the NPI, all subjects were shown to have scorable psychopathology. The percentages of patients having each NPI symptom in total are shown in Figure 1. The most common behavior was apathy (97.3%), followed by delusions (62.2%), irritability (59.5%), dysphoria (52.7%), anxiety (51.4%), aberrant motor behavior (47.3%), agitation (44.6%), disinhibition (31.3%), and hallucinations (25.7%). The least common behavior was euphoria (13.5%). The percentages of patients having each NPI symptom in the level of the CDR severity are shown in Table 2. The frequencies in agitation (c 2 = 9.6, P < 0.05), euphoria (c 2 = 19.5, P < 0.01) and aberrant Table 1. Subjects Number (M/F) Age (year) Mean ± SD MMSE Mean ± SD Total NPI score Mean ± SD CDR = (5/12) 72.9 ± ± ± 7.2 CDR = 1 33 (6/27) 77.0 ± ± ± 11.1 CDR = 2 17 (5/12) 77.4 ± ± ± 15.4 CDR = 3 7 (4/3) 75.9 ± ± ± 11.8 Total 74 (20/54) 76.0 ± ± ± 12.1 Total NPI score was calculated by adding all composite scores as a product of the frequency and severity subscores for each Neuropsychiatric Inventory domain. CDR, Clinical Dementia Rating; F, female; M, male; MMSE, Mini-Mental State Examination; NPI, Neuropsychiatric Inventory; SD, standard deviation.

3 276 J. Shimabukuro et al. Del n=74 Hal Agit Dys Anx Euph Apa Dis Irrit Motor % Figure 1. Prevalence of 10 behaviors in the Neuropsychiatric Inventory for all subjects. Prevalence was calculated as the frequency of patients who had a composite score more than 0. Values indicate a percentage (%). NPI, Neuropsychiatric Inventory; Del, delusions; Hal, hallucinations; Agit, agitation; Dys, dysphoria; Anx, anxiety; Euph, euphoria; Apa, apathy; Dis, disinhibition; Irrit, irritability; Motor, aberrant motor behavior. Table 2. Prevalence of 10 behaviors in the Neuropsychiatric Inventory across the Clinical Dementia Rating groups (%) Group Del Hal Agit Dys Anx Euph Apa Dis Irrit Motor CDR = CDR = CDR = CDR = Prevalence was calculated as the frequency of patients who had a composite score more than 0. Values indicate a percentage (%). Agit, agitation; Anx, anxiety; Apa, apathy; CDR, Clinical Dementia Rating; Del, delusions; Dis, disinhibition; Dys, dysphoria; Euph, euphoria; Hal, hallucinations; Irrit, irritability; Motor, aberrant motor behavior; NPI, Neuropsychiatric Inventory. motor behavior (c 2 = 18.2, P < 0.01) were significantly related to the level of CDR severity. However, other NPI symptoms were not related to the level of CDR severity. When compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, significant difference was found in frequency of euphoria (mild vs. moderate or severe, 2.0% vs. 37.5%, c 2 = 17.1, P < 0.01), disinhibition (22.0% vs. 50.0%, c 2 = 5.8, P < 0.05) and aberrant motor behavior (34.0% vs. 75.0%, c 2 = 11.3, P < 0.01), but no significant difference was found in frequency of delusions (64.0% vs. 58.3%), hallucinations (20.0% vs. 37.5%), agitation (42.0% vs. 50.0%), dysphoria (58.0% vs. 41.7%), anxiety (52.0% vs. 50.0%), apathy (96.0% vs. 100%), and irritability (60.0% vs. 58.3%). That is, the patients with AD with mild dementia (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as those with moderate or severe dementia (CDR 2 or 3). The mean (standard deviation) total NPI scores are shown in Table 1. There is significant difference in the total NPI scores between CDR groups with increasing the severity of BPSD as increasing the severity of dementia (c 2 = 8.2, P < 0.05). We demonstrate the mean scores of the NPI composite score for each behavioral domain in each CDR group in Figure 2. Composite scores in agitation (r = 0.28, P < 0.05), euphoria (r = 0.47, P < 0.01), apathy (r = 0.36, P < 0.01), disinhibition (r = 0.33, P < 0.01) and aberrant motor behavior (r = 0.49, P < 0.01) were significantly correlated with the level of CDR severity; the score was increased as the severity was increased (Table 3). However, other NPI symptoms were not correlated with the level of CDR severity. When compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, significant difference was found in the mean scores of the composite score for euphoria (mild vs. moderate or severe: 0.0 vs. 1.6,

4 Dementia and mild Alzheimers 277 Figure 2. The mean scores of the Neuropsychiatric Inventory composite score for each behavioral domain in each Clinical Dementia Rating group. A composite score for each domain was determined as the product of the frequency and severity subscores (maximum, 12). NPI, Neuropsychiatric Inventory; CDR, Clinical Dementia Rating; Del, delusions; Hal, hallucinations; Agit, agitation; Dys, dysphoria; Anx, anxiety; Euph, euphoria; Apa, apathy; Dis, disinhibition; Irrit, irritability; Motor, aberrant motor behavior. Mean Score Del Hal Agit Dys Anx Euph Apa Dis Irrit Motor CDR=0.5 CDR=1 CDR=2 CDR=3 Table 3. Correlation of Clinical Dementia Rating severity with scores of Mini-Mental State Examination, Total, and composite scores for each Neuropsychiatric Inventory domain Clinical Dementia Rating r P MMSE P < 0.01 Total P < 0.05 Del NS Hal NS Agit P < 0.05 Dys NS Anx NS Euph P < 0.01 Apa P < 0.01 Dis P < 0.01 Irrit NS Motor P < 0.01 Statistical analysis was performed using Spearman s correlation coefficient. Apa, apathy; Agit, agitation; Anx, anxiety; CDR, Clinical Dementia Rating; Del, delusions; Dis, disinhibition; Dys, dysphoria; Euph, euphoria; Hal, hallucinations; Irrit, irritability; MMSE, Mini-Mental State Examination; Motor, aberrant motor behavior; NPI, Neuropsychiatric Inventory; NS, not significant; Total, total NPI scores. U = 382.5, P < 0.01), apathy (3.7 vs. 5.5, U = 368.5, P < 0.01), disinhibition (0.5 vs. 1.6, U = 418.0, P < 0.01) and aberrant motor behavior (1.3 vs. 4.0, U = 310.5, P < 0.01), but no significant difference was found in the mean scores of the composite score for delusions (3.0 vs. 2.5), hallucinations (0.8 vs. 1.2), agitation (1.3 vs. 2.0), dysphoria (1.7 vs. 1.5), anxiety (1.8 vs. 2.1), and irritability (2.1 vs. 2.5; Table 4). That is, the mild AD groups (CDR 0.5 or 1) had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. DISCUSSION The present study demonstrates that apathy was the most frequent behavioral change in patients with AD, followed by delusions, irritability, dysphoria, anxiety, aberrant motor behavior, agitation, disinhibition and hallucinations, and that the least common behavior was euphoria. In the previous studies using the NPI, Mega et al. 12 reported that apathy was the most frequent behavioral change in AD, followed by agitation, anxiety, irritability, dysphoria and aberrant motor behavior, and that the least common behavior was euphoria. Hirono et al. 10 demonstrated that apathy was the most frequent, followed by aberrant motor behavior, delusions, dysphoria, irritability and euphoria. Vilalta-Franch et al. 13 also found the most frequent symptom to be apathy and the least frequent symptom was euphoria in patients with dementia. However, Choi et al. 14 found the former to be apathy but the latter to be hallucination in patients with dementia. The present study reconfirms the findings that apathy is the most frequent and euphoria is the most rare BPSD in AD patients, as most previous studies have demonstrated. In addition, we found that the patients with AD with mild dementia (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as those with moderate or severe dementia (CDR 2 or 3). There is some difference in the previous finding of Cummings et al. 4 They found that

5 278 J. Shimabukuro et al. Table 4. Comparison between the mild Alzheimer s disease groups and the moderate or severe Alzheimer s disease groups in the mean scores of the composite score of the Neuropsychiatric Inventory Mild AD groups (CDR = 0.5, 1) Moderate or severe AD groups (CDR = 2, 3) Mann-Whitney U-test Number (M/F) (11/39) (9/15) Del 3.0 ± ± 3.1 NS Hal 0.8 ± ± 2.1 NS Agit 1.3 ± ± 2.7 NS Dys 1.7 ± ± 2.1 NS Anx 1.8 ± ± 2.6 NS Euph 0.0 ± ± 2.5 P < 0.01 Apa 3.7 ± ± 2.6 P < 0.01 Dis 0.5 ± ± 2.2 P < 0.01 Irrit 2.1 ± ± 2.7 NS Motor 1.3 ± ± 3.4 P < 0.01 Statistical analysis was performed using Mann Whitney U-test. Values are presented as mean ± standard deviation. Agit, agitation; Anx, anxiety; Apa, apathy; Del, delusions; Dis, disinhibition; Dys, dysphoria; Euph, euphoria; F, female; Hal, hallucinations; Irrit, irritability; M, male; Motor, aberrant motor behavior; NS, not significant; NPI, Neuropsychiatric Inventory. the frequencies of agitation, dysphoria, anxiety, apathy and aberrant motor behavior were increased with the level of dementia severity defined by the MMSE. The difference in the sampling method may contribute to the difference in the prevalence of BPSD. The sample of Cummings et al. included non-ad patients whereas our sample was exclusively AD patients who attended the psychiatric ward in a general hospital for the first time. The total NPI scores were significantly increased with the level of CDR severity. This finding is consistent with that of Mega et al., 12 who found that the total NPI scores were significantly increased with the level of severity of dementia determined by the score of MMSE. In the present study, however, the composite scores of each behavioral domain showed a different pattern between the mild AD groups (CDR 0.5 or 1) and the moderate or severe AD groups (CDR 2 or 3). The composite scores of euphoria, apathy, disinhibition and aberrant motor behavior in the mild AD groups (CDR 0.5 or 1) were significantly lower than those in the moderate or severe AD groups (CDR 2 or 3). However, there was no significant difference in the composite score of delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Finally, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, we found that in the frequency of NPI, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and in the composite scores of NPI, the mild AD groups (CDR 0.5 or 1) had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. This finding indicates that psychotic symptoms (delusion and hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) may be the crucial BPSD in patients with mild AD as well as those with moderate or severe AD. These symptoms might be the target BPSD, for which it is urgently needed to develop the strategies of early intervention in the community and clinical settings. REFERENCES 1. Finkel SI, de Silva C, Cohen G et al. Behavioral and Psychological Signs and Symptoms of Dementia; A consensus statement on current knowledge and implications for research and treatment. Int. Psychogeriatr. 1996; 8: Pruchno RA, Michaels JE. Predictors of institutionalization among Alzheimer victims with caregiving spouses. J. Gerontol. 1990; 45: S259 S Steele C, Rovner B, Chase GA et al. Psychiatric symptoms and nursing home placement of patients with Alzheimer s disease. Am. J. Psychiatry 1990; 147:

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