A Study of Delusions in a Large Cohort of Alzheimer's Disease Patients

Rockwell, Enid; Jackson, Edward M.; Vilke, Gary M.; Jeste, Dilip V.

doi:10.1097/00019442-199405000-00009

Cited by 39 publications

(44 citation statements)

References 21 publications

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“…Similar to a study by Loreck et al (1994) showing a positive correlation between delusions and BDS scores (Blessed et al, 1968), we found that patients with CS showed more pronounced limitations in activities of daily living. Our results are also consistent with a study by Rockwell et al (1994) that indicated a greater likelihood of self-care problems among patients with delusions compared to those without delusions. Thus, delusions such as the Capgras type may impact the patient's ability to engage in important self-maintenance behaviors such as eating, dressing and continence.…”

Section: Discussionsupporting

confidence: 92%

Prevalence and correlates of Capgras syndrome in Alzheimer's Disease

Harwood

Barker

Ownby

et al. 1999

Int. J. Geriat. Psychiatry

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Section: Discussionsupporting

confidence: 92%

Prevalence and correlates of Capgras syndrome in Alzheimer's Disease

Harwood

Barker

Ownby

et al. 1999

Int. J. Geriat. Psychiatry

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“…A number of studies have found that AD þ P subjects, in comparison to AD subjects without psychosis, demonstrate more severe cognitive and functional deficits, [61][62][63][64] and more rapid cognitive decline. 10,[12][13][14]65 Thus, in AD, psychosis presence is a marker for a cognitive risk phenotype.…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease

Devlin

et al. 2005

Mol Psychiatry

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Psychotic symptoms in subjects with Alzheimer disease (AD with psychosis, AD þ P) define a phenotype characterized by greater cognitive burden than in AD without psychosis. We have proposed that genes of small effect may contribute to the risk for expression of psychosis in multiple disorders, including AD. Recently, sex-differential association of a three-locus haplotype, including a G-A transition at codon 108/158 of catechol-O-methyltransferase (COMT) resulting in a Val-Met substitution, has been reported to confer an increased risk for schizophrenia. The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis. All subjects were characterized for alleles at the three loci associated with schizophrenia, RS737865, COMT G-A 108/158 (RS4680), and RS165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Both single locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci. All analyses were stratified by sex. In female subjects, RS4680 demonstrated a modest association with AD þ P; RS737865 demonstrated a trend towards an association. There was a highly significant association of AD þ P with the four-locus haplotype, which resulted from additive effects of alleles at RS4680 and ERE6 (or RS737865, as this locus was in almost absolute linkage disequilibrium (LD) with ERE6). In male subjects, no single locus test was significant, but there remained a strong association between AD þ P and the four-locus haplotype. This association appeared to result from interaction of the ERE6/ RS737865, RS4680, and RS165599 loci. Genetic variation in COMT is associated with AD þ P, and thus appears to contribute to psychosis risk across disorders. Sex-differential associations of COMT with psychosis may result from variation at, or in LD with, ERE6. Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted.

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“…AD þ P has been associated with more severe cognitive and functional deficits in AD subjects matched on other clinical characteristics. [30][31][32][33][34] Studies conflict regarding whether AD þ P is associated with more rapid cognitive deterioration, though most have found an association. 19,[35][36][37][38] It should be noted that most of these studies have not controlled for the duration of AD prior to study entry.…”

Section: Evidence For a Distinct Phenotypementioning

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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A Study of Delusions in a Large Cohort of Alzheimer's Disease Patients

Cited by 39 publications

References 21 publications

Prevalence and correlates of Capgras syndrome in Alzheimer's Disease

Prevalence and correlates of Capgras syndrome in Alzheimer's Disease

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease

Psychotic symptoms in Alzheimer disease: evidence for a distinct phenotype

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