Factors associated with psychotic symptoms in Alzheimer's disease

Hirono, Nobutsugu; Mori, Etsuro; Yasuda, Minoru; Ikejiri, Yoshitaka; Imamura, Toru; Shimomura, Tatsuo; Ikeda, Manabu; Hashimoto, Mamoru; Yamashita, Hikari

doi:10.1136/jnnp.64.5.648

Cited by 89 publications

(79 citation statements)

References 43 publications

(42 reference statements)

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“…However, the most frequent positive association has been between e4 and psychotic symptoms. Fifteen studies (including the present one) have examined psychotic symptoms, and six (including the present one) have reported that e4 increased the risk for psychosis (Ramachandran et al, 1996;Ballard et al, 1997;Harwood et al, 1999;Weiner et al, 1999;Scarmeas et al, 2002), whereas nine have found no effect of e4 (Lehtovirta et al, 1996a;Cacabelos et al, 1997;Lopez et al, 1997;Lyketsos et al, 1997;Hirono et al, 1998Hirono et al, , 1999Levy et al, 1999;Gabryelewicz et al, 2002;Sweet et al, 2002). Among the six positive studies only two others (Weiner et al, 1999;Scarmeas et al, 2002) have considered delusions and hallucinations separately.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 68%

“…By contrast, Weiner et al (1999) reported marginal (P ¼ 0.05) positive associations between ApoE e4 and both delusions and hallucinations. This may reflect a statistical power issue, since delusions are more prevalent among AD patients than hallucinations (Hirono et al, 1998;Bassiony and Lyketsos, 2003), including in our present sample Note: NPI, neuropsychiatric inventory. OR (odds ratio) and 95% CI are for the effect of e4 carrier status in multiple logistic regression models, with NPI subscores as dependent variables and the following additional independent variables: age, sex, education, and MMSE.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 86%

“…Previous studies have used a variety of methods to identify psychotic symptoms in their subjects, including general clinical examination (Lehtovirta et al, 1996a;Lyketsos et al, 1997;Hirono et al, 1999), rating scales (Ballard et al, 1997;Cacabelos et al, 1997;Hirono et al, 1998;Levy et al, 1999;Weiner et al, 1999;Gabryelewicz et al, 2002;Scarmeas et al, 2002), or a combination (Ramachandran et al, 1996;Lopez et al, 1997;Sweet et al, 2002). Those studies that have employed research rating scales have used a wide range of scales (see Table 4), making it difficult to reconcile discrepant reports.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

“…Given the well-documented increase in psychotic symptoms with AD severity (Lopez et al, 1997;Hirono et al, 1998;Harwood et al, 1999;Gabryelewicz et al, 2002), variations in subject disease stage may represent an important difference among studies. Harwood et al (1999), observed that the elevated risk for psychosis was present specifically at the severe stage (MMSEo12) of cognitive impairment among AD patients carrying the e4 allele.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

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Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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The apolipoprotein E (ApoE) e4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE e4 + and e4-AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n ¼ 266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE e4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on e4 effects and to examine the association between e4 and other behavioral symptoms. ApoE e4 was significantly associated with psychotic symptoms (odds ratio (OR) ¼ 1.87, 95% CI ¼ 1.07-3.29, P ¼ 0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between e4 and delusions. The e4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE e4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

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Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 68%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 86%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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“…70 We are unaware, however, of reports of similar pedigrees for AD þ P. A number of investigations have examined whether APOE4 might contribute to the AD þ P phenotype. While one large and two smaller studies have found an association of APOE and AD þ P, [85][86][87] most reports have found no association of APOE4 with AD þ P. 33,[88][89][90][91][92][93] Furthermore, though the major effect of APOE4 on AD phenotype is to reduce age-ofonset of AD, 94 APOE4 genotype is not associated with reduced time to onset of AD þ P. 95 Nor was association of increased risk for AD þ P with the putative AD risk gene, alpha-1-antichymotrypsin (ACT) detected. 95 Similarly, there is no evidence that any of the risk genes found to be associated with AD þ P in casecontrol studies (see above) also contribute to AD risk.…”

Section: Cosegregation Of Ad þ P and Idiopathic Psychosesmentioning

confidence: 99%

Psychotic symptoms in Alzheimer disease: evidence for a distinct phenotype

et al. 2003

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Though efforts to identify the genetic etiology of Alzheimer disease (AD) have made substantial progress, to date only some of the genes contributing to AD risk have been identified. Utilization of more etiologically homogeneous subphenotypes represents one strategy to facilitate the identification of novel risk genes in complex disorders. In this review, we evaluate the hypothesis that psychotic symptoms, such as delusions and hallucinations, define a suitable subphenotype in AD patients for gene-mapping efforts. Psychotic symptoms occur in 40-60% of patients with AD and are associated with more severe cognitive deficits and a more rapidly deteriorating course. The presence of psychotic symptoms in AD confers increased risk of similar symptoms to affected siblings. Candidate gene association analyses and initial linkage analysis have yielded significant results. We discuss possible genetic models of psychotic symptoms in AD, and suggest strategies for further investigation. Identification of such genetic factors may facilitate gene-mapping studies for both AD and idiopathic psychoses. OverviewThe genetic basis of Alzheimer disease (AD) is unknown, although considerable strides have been made using gene-mapping efforts. Success has been most notable for the highly heritable early onset form, which comprises a minority of the entire population of AD cases. 1 While the impact of apolipoprotein E e4 alleles (APOE4) is well established, the genetic architecture of the more common late-onset AD (LOAD) is unclear. Like other genetically complex disorders, such as diabetes mellitus, progressively greater attention has been paid to utilizing defined subgroups of AD (eg late age-of-onset, APOE4 presence, autopsy confirmation) for mapping liability genes. 2,3 We have previously proposed that the presence of psychotic symptoms, delusions and hallucinations, define a subgroup of AD 4 that may be suitable for genetic investigation. 5,6 To our knowledge, however, the available evidence pertaining to whether AD with psychosis (AD þ psychosis (AD þ P)) identifies a phenotype suitable for genetic study has not been the subject of critical review.Stedman's Medical Dictionary defines phenotype as 'the observable characteristics, at the physical, morphologic, or biochemical level, of an individual, as determined by the genotype and environment '. 7 The genes associated with a behavioral phenotype, however, are unknown. The task for the psychiatric geneticist, therefore, is to identify a behavioral phenotype that varies according to alleles at a restricted set of genes. As in all psychiatric nosology, a behavioral phenotype must be readily and reliably identifiable in all patients of interest. If this behavioral phenotype has clinical relevance (eg bipolar illness) it provides a measure of face validity, and adds significance to its use in the search for causative genes. Tsuang et al. 8 enumerated additional criteria for determining that a behavioral phenotype has a substantial genetic basis, including state independence, biolog...

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