delusions of japanese patients with alzheimer's disease

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY

Int J Geriatr Psychiatry 2003; 18: 527–532.

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.864

Delusions of Japanese patients with Alzheimer’s disease

Manabu Ikeda1*, Kazue Shigenobu1, Ryuji Fukuhara1, Kazuhiko Hokoishi1, Akihiko Nebu1,Naruhiko Maki1, Michie Nomura1,2, Kenjiro Komori1 and Hirotaka Tanabe1

1Department of Neuropsychiatry, Ehime University School of Medicine, Ehime, Japan2Ehime College of Health Science, Ehime, Japan

SUMMARY

Background Delusions constitute one of the most prominent psychiatric complications in Alzheimer’s disease (AD).However, there is little consensus of the prevalence and associated factors for delusions in AD.Aims To reveal the characteristics of delusions among Japanese patients with AD.Method 112 consecutive patients with AD were recruited over a one year period and administered the NeuropsychiatricInventory (NPI).Results Delusions were present in 53 patients (47.3%). Delusions of theft were the most common type of delusion (75.5%of patients with delusions), followed by misidentification delusions and delusions of suspicion. More hallucination, agita-tion, and female gender were found in the delusions group.Conclusions The authors found a high frequency of delusions, particularly of delusions of theft and suggested that genderwas associated with the expression of delusions in Japanese patients with AD. Copyright # 2003 John Wiley & Sons, Ltd.

key words— Alzheimer’s disease; delusion; dementia; NPI

Untreated psychosis and disruptive behaviors indementia are distressing to patients and caregivers(Rabins et al., 1982; Haupt et al., 1996) and often leadto institutionalization (Steele et al., 1990; Haupt andKurz, 1993). Appropriate management of behavioralsymptoms lessen the burden of caregivers (Shigenobuet al., 2002) and may postpone institutionalization.Therefore, evaluation of psychosis and behavioralsymptoms in dementia are of considerable importancein practice. Despite the importance of specific medi-cation and care for each neuropsychiatric disturbance,neurobehavioral symptoms of delusions, hallucina-tions, and these subtypes have been consideredtogether in most previous studies (Bassiony et al.,2000; Paulsen et al., 2000).

In Alzheimer’s disease (AD), delusions constituteone of the most prominent psychiatric complications(Migliorelli et al., 1995), and were reported in theinitial case description by Alzheimer (1907). How-ever, they have received much less attention than cog-

nitive impairment. Risk factors for development ofdelusions in AD, such as sociodemographic charac-teristics and cognitive impairment, are still controver-sial (Ballard and Oyebode, 1995; Rao and Lyketsos,1998). In this study, we address the prevalence, asso-ciated factors and type of delusions in Japanesepatients with AD and compare these results with thoseof Western countries. If there are differences betweenthe results in Japan and those in Western countries, wemight presume the influence of sociocultural differ-ences, as well as biological factors, for developmentof delusions in AD.

METHOD

Subjects

Study participants were consecutive outpatients witha diagnosis of AD who were referred for evaluation tothe Higher Brain Function Clinic for outpatients ofthe university hospital of Ehime University Schoolof Medicine, between January 1996 and May 2000.Among 344 consecutive patients, 112 patients (41men and 71 women; mean (s.d.) age, 73.8 (9.4) years;mean (s.d.) education history, 9.3 (2.1) years) satisfied

Received 15 January 2002Copyright # 2003 John Wiley & Sons, Ltd. Accepted 10 February 2003

* Correspondence to: Dr M. Ikeda, Department of Neuropsychiatry,Ehime University School of Medicine, Shigenobu, Onsen-gun,Ehime 791-0295, Japan. Tel: þ81-89-960-5315. Fax: þ81-89-960-5317. E-mail: [email protected]

the NINCDS/ADRDA diagnostic criteria (McKhannet al., 1984) for probable AD and had no lesion otherthan diffuse cerebral atrophy as evidenced by cranialmagnetic resonance imaging (MRI). None of thepatients had a history of stroke, alcoholism, depres-sion, or manic state before the onset of dementiaand received no neuroleptics and cholinesterase inhi-bitors. Patients underwent both physical and neurolo-gical examinations, and were assessed with acomprehensive neuropsychological test battery,including the Mini-Mental State Examination(MMSE) for an evaluation of general intelligence(Folstein et al., 1975), the Short-Memory Question-naire (SMQ) for an evaluation of memory function(Koss et al., 1993; Maki et al., 1998) and ClinicalDementia Rating (CDR) for an evaluation of demen-tia severity (Hughes et al., 1982). Affective and beha-vioral disorders were assessed by the Neuro-psychiatric Inventory (NPI) (Cummings et al., 1994;Hirono et al., 1997). Laboratory blood tests includingvitamin B12 and thyroid function, electroencephalo-graphy, and MRI and/or functional imaging(HMPAO-SPECT) were performed, resulting in nofindings indicative of any disease other than AD. Thisstudy was conducted after obtaining informed consentfrom all subjects or their caregivers.

Assessment of delusions

We assessed the presence of delusions by a structuredcaregiver interview using the delusion subscale of theNPI. We also assessed different types of delusionsusing subquestions from this subscale. The NPI hasproven validity and reliability both in Western coun-tries (Cummings et al., 1994) and Japan (Hirono et al.,1997). A patient was considered to have delusionsonly if he or she held the same delusion within theprevious 4 weeks. Transient delusions secondary todelirium, drug toxicity, or other acute factors were

excluded by follow-up examination at least everythree months. Particular care was taken to differenti-ate delusions in AD from those in dementia withLewy bodies. Patients who have prominent visual hal-lucinations, prominent parkinsonism, and a fluctuat-ing level of consciousness in addition to a history offalls were excluded. Patients who had never experi-enced delusions were considered nondelusional. TheNPI, the MMSE, the SMQ and CDR were adminis-tered on the same day.

Statistical analysis

Patients with and without delusions were comparedby using Student’s two-tailed t-tests (for continuousvariables: age, education history, duration of illness,MMSE score, SMQ score), Mann-Whitney U tests(for each NPI subscale score), and chi-square tests(for variables of gender and CDR staging). To explorethe possible associated factors of delusions, a logisticregression analysis was used with the presence ofdelusions as the dependent variables, and age, gender,education, duration of illness, and a measure of func-tional impairment as the independent variables. Toexplore the possible associated factors of the presenceof delusions of theft, the same analysis was employed.Analyses were repeated with either MMSE, SMQ orCDR score enrolled into the model. A significancelevel of 0.05 (two-tailed) was set for all analyses,which were performed by using SPSS for Windows,version 8.0.

RESULTS

Delusions were present in 53 patients (47.3%). 59patients were free from delusions. Demographic andpsychometric characteristics for patients with andwithout delusions are presented in Table 1. Significantdifferences were found between these two groups interms of gender (�2¼ 6.3, df¼ 1, p¼ 0.0119).

Table 1. Demographic and psychometric characteristics for patients with and without delusions

Characteristic Delusions No delusions p-value(n¼ 53) (n¼ 59)

Age, years 75.2� 7.8 72.5� 10.5 0.1337Sex, female:male 40:13 31:28 0.0119Education, years 9.1� 1.9 9.5� 2.3 0.3552Duration of illness, years 3.8� 1.9 3.9� 2.4 0.2142CDR, grade 0.5:1:2:3 8:26:10:9 6:34:11:8 0.7673MMSE score 16.2� 6.6 17.4� 6.5 0.3151SMQ score 17.0� 9.9 18.9� 6.6 0.3146

Note: Values are mean�SD unless otherwise indicated.CDR¼Clinical Dementia Rating; MMSE¼Mini-Mental State Examination; SMQ¼ Short-Memory Questionnaire; NPI¼Neuropsychia-tric Inventory.

528 m. ikeda et al.

Copyright # 2003 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2003; 18: 527–532.

Female gender was positively associated with thedelusions group. No significant differences werefound between those with and without delusions interms of age, years of education, duration of illness,cognitive impairment, or severity of dementia. Thelogistic regression analyses with MMSE scoreenrolled into the model revealed that only gender sig-nificantly predicted the delusions (OR¼ 0.2826;95%CI¼ 0.1182 to 0.6756; p¼ 0.0045). Similarresults were obtained when either SMQ or CDR wereused in the model instead of MMSE. The relationshipbetween delusions and other psychiatric symptomswas examined. Significant differences were foundbetween those two groups with and without delusionsin terms of hallucinations (U¼ 1058.5, n¼ 112,p< 0.01) and agitation (U¼ 1058.5, n¼ 112,p< 0.01). More hallucinations and agitation wereassociated with the delusions group.

The types of delusions are summarized in Table 2.Of the 53 patients with delusions, 40 (75.5%) haddelusions of theft, 16 (30.2%) had misidentificationdelusions, e.g. ‘someone is in the house’, and 10(18.9%) had delusions of suspicion. A number ofpatients had more than one type of delusion.

Of the patients with delusions, 40 had delusions oftheft and 13 did not have delusions of theft. The logis-tic regression analyses with MMSE score enrolledinto the model revealed that the following factorswere associated with delusions of theft; gender(OR¼ 0.0863; 95%CI¼ 0.0112 to 0.6655; p¼0.0187) and MMSE (OR¼ 1.3484; 95%CI¼ 1.1202to 1.6230; p¼ 0.0016). Similar results were obtainedwhen SMQ or CDR were used instead of MMSE in

the model [gender (OR¼ 0.0855; 95%CI¼ 0.0127 to0.5764; p¼ 0.0115) and SMQ (OR¼ 1.2385;95%CI¼ 1.0693 to 1.4346; p¼ 0.0043): gender(OR¼ 0.1165; 95%CI¼ 0.0196 to 0.6936; p¼0.0182) and CDR (OR¼ 0.1560; 95%CI¼ 0.0503 to0.4842; p¼ 0.0013), respectively]. Female genderand higher cognition levels were associated with delu-sions of theft, although we could not specify the kindof cognition that was particularly correlated with delu-sions of theft.

DISCUSSION

This study is one of the most comprehensive and pre-cise surveys of delusions in AD in Japan and Asia.Delusions were present in about half of the patients.Delusions of theft were the most common type ofdelusion, followed by misidentification delusions,e.g. ‘someone is in the house’ and delusions of suspi-cion. More hallucination, agitation, and female gen-der were found in the delusions group. Nosignificant differences were found between those withand without delusions in terms of age, years of educa-tion, duration of illness, cognitive impairment, orseverity of dementia.

We report that 47.3% of AD patients exhibiteddelusions. These findings are well within the rangereported in previous studies (Wragg and Jeste, 1989;Rubin, 1992; Rockwell et al., 1994; Ballard andOyebode, 1995; Migliorelli et al., 1995; Mega et al.,1996; Ozawa, 1997; Hirono et al., 1998; Rao andLyketsos, 1998; Wilson et al., 2000). However, esti-mates of the prevalence of delusions vary widely,

Table 2. Types of delusions in 53 patients with delusions

Type No. Age Gender Education Duration MMSE SMQ CDR(years) (M:F) (years) (years) (grade

0.5:1:2:3)

Persecutory delusionsPeople are stealing things 40 75.4 (7.1) 6:34 9.2 (2.0) 3.9 (2.1) 18.0 (5.2) 19.3 (9.9) 8:23:5:4from patientPatient is being conspired against or 10 74.5 (11.5) 3:8 8.5 (2.1) 3.6 (1.2) 12.2 (9.2) 14.2 (6.8) 2:2:3:3harassedPatient has been abandoned 2 79.4 (3.3) 2:0 8.5 (2.5) 3.5 (1.5) 7.0 (5.0) 7 (3) 0:0:1:1

Misidentification delusionsSomeone is in the house 16 75.9 (4.7) 7:9 8.4 (1.4) 3.4 (1.3) 14.3 (7.4) 15.9 (9.8) 1:6:4:5Spouse and others are not who they 1 89.7 0:1 6 3.7 20 16 0:1:0:0claim to beThe house is not the patients own house 5 76.6 (2.3) 3:2 8.2 (1.6) 3.9 (2.3) 11.6 (5.0) 9.4 (4.8) 0:0:3:2Television figures are actually present in 4 77.9 (8.7) 1:3 8.0 (2.4) 3.7 (0.8) 17.0 (9.0) 17.5 (9.1) 1:2:0:1the home

Delusional jealousy 6 81.0 (4.2) 3:3 8.7 (1.8) 3.0 (1.5) 13.8 (7.0) 21.0 (12.6) 1:3:0:2Others 10 75.7 (7.7) 5:5 8.8 (1.8) 5.0 (1.8) 15.9 (7.0) 14.9 (6.0) 0:3:3:2

Note: Values are mean (SD) unless otherwise indicated. A number of patients had more than one type of delusion.

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from 10% (Birkett, 1972) to 73% (Leuchter and Spar,1985) of AD patients among studies. Several metho-dological limitations such as the lack of operationalcriteria of dementia and/or structured psychiatricinterviews, the retrospective nature of some studies,or small sample size, may account for these dis-crepancies (Ballard and Oyebode, 1995; Rao andLyketsos, 1998). There seems to be no geographicaldifferences in the frequency of delusions with ADpatients between Western countries and Japan,although many studies did not use specificallydesigned instruments for delusions, which makes itdifficult to make direct comparisons.

Delusions of theft were the commonest type ofdelusion, followed by misidentification delusionsand delusions of suspicion. A systematic study ofthe prevalence of different types of delusions in alarge series of consecutive AD patients has rarelybeen carried out (Migliorelli et al., 1995). Accordingto Ballard and Oyebode’s review (1995) of 70 studiespertaining to psychotic symptoms in patients withdementia, nine studies reported the prevalence of spe-cific individual delusions. By their very approximateestimation, the most common symptoms in rank orderwere delusions of theft, delusions of suspicion, delu-sions of reference, delusions of strangers in the house,and so on. In Japan, Ozawa (1997) assessed inpatientswithout using structured instrument for subtypes ofdelusions, finding a total of 73 subjects with AD,56.2% of whom had psychotic symptoms and 46.7%of whom had delusions of theft. Hirono et al. (1998)also assessed inpatients with behavioral pathology inAD rating scale or the NPI, findings a total of 228 sub-jects with AD, 51.8% of whom had psychotic symp-toms and 38.6% of whom had delusions of theft. Itappears that a consensus has emerged from both Wes-tern and Japanese studies, with the most frequentdelusion in AD patients being delusion of theft.

In this study, female predominance was evident indelusions and particulary in delusions of theft. Severalstudies have addressed the relationship between thedevelopment of psychotic symptoms in dementia suf-ferers and their gender. Rockwell et al. (1994) found asignificant association between female gender and thepresence of delusions, whereas Burns et al. (1990)reported a higher prevalence of delusions in males.The majority of studies in Western countries havenot found any association between gender and thepresence of delusions (Bassiony et al., 2000),although there is an inadequate amount of informa-tion given to allow for the calculation of a gender dif-ference in many reports (Rockwell et al., 1994). Onthe contrary, it was generally believed that, in Japan,

gender was associated with the expression of delu-sions. Psychotic symptoms (Asai et al., 1982; Kido,1989; Ozawa, 1997; Hirono et al., 1998), delusions(Kasahara, 1992), and delusions of theft (Takenaka,1993; Ozawa, 1997) were more common in femalesthan males. The divergence of findings in Japan andWestern countries may be due to methodological dif-ferences or sociocultural differences between studies.Our study will be comparable to future Westernreports because we used the NPI to assess delusions.For sociocultural factors, the gender difference of thecontribution to household matter between Japan andWestern countries might be important when analysingthe female predominance in delusions and, in par-ticular, delusions of theft in Japanese studies. TheJapanese male’s contribution rate of the householdmatter is less than half of Western male’s rate (GenderEquality Bureau, 2000). 77.3% of Japanese femalesover 50 years of age manage their family livingexpenses alone (Ehime Women’s Foundation, 2000).Biological aspects such as cortical dysfunction(Ponton et al., 1995; Staff et al., 1999; Fukuharaet al., 2001) as well as psychosocial and environmen-tal aspects such as the contribution rate to householdmatter and living with or without caregivers as wellas biological aspects such as cortical dysfunction(Ponton et al., 1995; Staff et al., 1999; Fukuharaet al., 2001) may be important to consider when toexploring AD delusions in future studies.

This study found that the occurrence of delusionsof theft was related to higher levels of cognitive func-tion. However, we could not correlate the specificcognitive function with the delusions of theft. Therelationship of cognitive function to the occurrenceof psychiatric symptoms is still controversial (Wraggand Jeste, 1989; Ballard and Oyebode, 1995). A fewstudies suggest that delusions are more likely to occurin patients with higher levels of cognitive function(Cummings et al., 1987; Binetti et al., 1993) whileothers suggest delusional groups are significantlyimpaired on cognitive tests such as the MMSE (Jesteet al., 1992; Harwood et al., 2000; Wilson et al.,2000). Other studies suggest that there is no associa-tion between delusions and cognitive impairment(Teri et al., 1988; Burns et al., 1990; Deutsch et al.,1991; Migliorelli et al., 1995; Bassiony et al.,2000). There were few studies that examined the rela-tionship between subtypes of delusions and cognitivefunction. There may be delusion-specific effects thatare confined to specific cognitive domains. Althoughthe small sample size of the delusions groups otherthan the delusions of theft limits the analysis of thegroups in this study, it is important to investigate

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the association between subtypes of delusions andsome specific aspects of cognitive impairment. Infuture studies, it will be essential to use specializedneuropsychological tests that assess memory, orienta-tion, attention, and visuospacial ability.

As compared to AD patients without delusions, ADpatients with delusions in this study had more hallu-cinations and agitation. There has been a consensusthat delusions and/or hallucinations are associatedwith an increase of aggression (Cooper et al., 1991;Deutsch et al., 1991; Gilley et al., 1991; Forstl et al.,1993; Bassiony et al., 2000), and agitation (Cooperet al., 1991; Gilley et al., 1991; Rockwell et al.,1994). Delusions, aggression, and agitation areimportant factor that increases the burden of carefor demented patients, as a number of studies havereported (Greene et al., 1982; Coen et al., 1997; Teri,1997; Kaufer et al., 1998; Nagaratnam et al., 1998;Shigenobu et al., 2002). There is evidence to supporta link between psychotic symptoms and admissionto residential care in community-dwelling dementiasufferers (Steele et al., 1990). Delusions may be anindication of other behavioral disturbances. Correctevaluations and treatment of delusions and associatedbehavioral disturbances may delay institutionaliza-tion and lower caregiver burden.

ACKNOWLEDGMENTS

We would like to thank Dr G. E. Berrios and Dr P.Nestor for their valuable comments.

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