Phenomenology and clinical correlates of delusions in Alzheimer disease.

OBJECTIVES: The objectives of this study were to determine whether anosognosia, depression, and elevated mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized diagnostic criteria for psychosis of dementia. METHOD: The authors assessed a consecutive series of 771 patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood. RESULTS: Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and depression were significantly and independently associated with the presence of delusions, whereas elevated mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt aggression, and agitation. CONCLUSIONS: Anosognosia, depression, global cognitive deficits, and elevated mood are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.     

Regional brain atrophy in patients with mild Alzheimer's disease and delusions

BACKGROUND AND OBJECTIVE: The pathophysiology and the neurobiology of the behavioral disturbances in Alzheimer's disease (AD) are far from understood. The aim of the study was to assess whether delusional AD patients have a specific pattern of regional brain atrophy. METHODS: The setting of the study was the outpatient facility of a memory clinic. Subjects were 41 AD patients with mild dementia severity (Mini-Mental State Exam score of 22 +/- 3, range 18 to 27). Delusions were assessed with the pertinent subscale of the UCLA Neuropsychiatric Inventory (NPI). Nondelusional (n = 22) AD and delusional (n = 19) AD were defined on the basis of absence (NPI delusions subscale = 0) or presence (NPI delusions subscale = 1 or higher) of delusions. Thirteen (68%) of the delusional patients had isolated theft delusions, and 6 (32%) had theft associated with another paranoid delusion (of jealousy or persecution). None of the patients had misidentifications or other delusions of nonparanoid content. Temporal lobe and frontal lobe atrophy were assessed with linear measures (radial width of the temporal horn, rWTH, and frontal index, FI) taken from computed tomographic films. Temporal and frontal asymmetries were computed as right/left ratio of the rWTH and FI. RESULTS: AD patients without delusions had symmetrical enlargement of both temporal (8.1 +/- 3.9 vs. 8.5 +/- 4.5) and frontal horns (35.8 +/- 4.8 vs. 35.9 +/- 4.6). On the contrary, AD with delusions showed temporal horns larger to the right (9.1 +/- 3.3 vs. 7.7 +/- 3.1, p = .06) and the frontal horn to the left (35.7 +/- 4.3 vs. 37.5 +/- 4.2, p = .02). This different pattern was confirmed with a gender-adjusted repeated measures analysis of variance model interaction term between asymmetry and group: F1,38 = 5.5, p = .03). DISCUSSION: AD patients with delusions are characterized by a specific pattern of frontal and temporal asymmetry of brain atrophy, whereas nondelusional patients are symmetric. Because the asymmetry pattern of the delusional patients is similar to the physiological pattern of asymmetry of individuals without dementia, the data indicate that the absence of theft delusions in the mild stage of AD rather than their presence is associated with an abnormal asymmetry pattern.     

The psychotic phenomenon in probable Alzheimer's disease: a positron emission tomography study

Positron emission tomography was used to examine the mechanisms of the psychotic phenomenon in Alzheimer's disease (AD). Data from 2 patients with delusions and 2 with hallucinations were compared with those of 5 AD patients without psychosis. The patients with paranoid delusions had diminished relative regional cerebral blood flow (rel-CBF) in the left dorsolateral prefrontal and left medial temporal cortices. The patients with visual hallucinations showed diminished rel-CBF in the right parietal, left medial temporal, and left dorsolateral prefrontal cortices. These findings support the hypothesis that a frontal-temporal abnormality is associated with paranoid delusions in AD. By contrast, visual hallucinations are associated with parietal as well as frontal and temporal lobe dysfunction. In these patients, a left prefrontal-temporal cortex dysfunction appears to be a common denominator for the development of the psychotic phenomenon in AD.     

Temporal lobe asymmetry in patients with Alzheimer's disease with delusions

OBJECTIVE: To test the hypothesis that delusions are associated with asymmetric involvement of the temporal lobe regions in Alzheimer's disease. METHODS: Temporal lobe atrophy was assessed with a linear measure of width of the temporal horn (WTH) taken from CT films. Temporal asymmetry was computed as the right/left (R/L) ratio of the WTH in 22 non-delusional and 19 delusional patients with Alzheimer's disease. Delusional patients had paranoid delusions (of theft, jealousy, persecution). None of the patients had misidentifications or other delusions of non-paranoid content. RESULTS: The R/L ratio indicated symmetric temporal horn size in the non-delusional (mean 1. 05 (SD 0.20), and right greater than left temporal horn in the delusional patients (mean 1.30, (SD 0.46); t=2.27, df=39, p=0.03). When patients were stratified into three groups according to the R/L ratio, 47% of the delusional (9/19) and 14% of the non-delusional patients (3/21; chi(2)=5.6, df=1, p=0.02) showed right markedly greater than left WTH. CONCLUSIONS: Predominantly right involvement of the medial temporal lobe might be a determinant of paranoid delusions in the mild stages of Alzheimer's disease.     

The epidemiology of psychosis in dementia.

OBJECTIVE: Authors compared delusions, hallucinations, and misidentification delusions in Alzheimer disease (AD) and vascular dementia (VaD) patients. METHODS: The authors report data on the prevalence, severity, clinical, and demographic associations of these symptoms in a population sample of 260 persons with dementia, examined with the Neuropsychiatric Inventory. RESULTS: The primary finding was that there was no difference in psychosis as a whole, or in delusions and hallucinations, between AD and VaD. Also, in AD, female gender appeared to be a risk factor for delusions; subjects in an earlier stage of dementia showed fewer delusions. CONCLUSION: The profile of delusions and hallucinations seen is different from that seen in schizophrenia, further supporting the hypothesis that AD-associated psychosis is a distinct phenomenological syndrome.     

Delusions in Alzheimer's disease and multi-infarct dementia

Neuropsychiatric symptoms such as delusions and misidentifications have been reported in dementia ranging from 10% to 73% in Alzheimer's disease (AD) patients and up to 40% in multi-infarct dementia (MID) patients. The aim of this study was to investigate in 61 AD and 31 MID patients both the frequency and the content of delusions during the course of illness and to evaluate the relationship between these and both functional and mental decline. The results indicated that delusion experiences had occurred in 45% of AD patients and in 38% of MID patients, occurring most frequently during the first year of illness. Patients who experienced psychiatric symptoms showed higher mini mental state examination scores and were less impaired in functional disability measures. With regard to the content, no significant differences were observed between AD and MID patients; 53% of psychotic symptoms were found to be paranoid delusions while 47% were misidentification delusions.     

White matter changes associated with psychotic symptoms in Alzheimer's disease patients

This study explored the relationship between white matter changes seen on magnetic resonance imaging (MRI) and neuropsychiatric symptoms of Alzheimer's disease patients. Fifty-five probable Alzheimer's disease patients were assessed with Behavioral Rating Scale for Dementia (BRSD) and MRI. White matter changes in the bilateral frontal or parieto-occipital region and left basal ganglia significantly corresponded with the score of the Psychotic Symptoms subscale of BRSD. Secondary analyses revealed that white matter changes were not associated with paranoid delusion and hallucination, but only with delusional misidentification. Our results suggest that white matter changes in Alzheimer's disease patients probably contribute to the development of specific psychotic symptoms, namely delusional misidentification.     

Disturbances of person identification in Alzheimer's disease. A retrospective study.

Person identification disturbances in Alzheimer's disease (AD) add to the suffering of both patients and caregivers. We assessed the prevalence of person identification disturbances in the records of 217 outpatients with AD. These disturbances occurred in 25.4% (N = 55) and included transient misidentifications of familiar persons (N = 34), the Capgras syndrome (N = 11), misidentification of themselves in mirrors (N = 5), prosopagnosia (N = 3), misidentification of unfamiliar persons as familiar (N = 1), and misidentification of another person as oneself (N = 1). Transient misidentifications were easily corrected misperceptions, and the Capgras syndrome and mirror difficulties were associated with suspiciousness/paranoia and delusions. In AD, these findings suggest that misidentifications of familiar persons result from misinterpretations due to cognitive impairments, and the Capgras syndrome and mirror difficulties ensue when these misinterpretations are elaborated by paranoid delusions.     

Origins of delusions in Alzheimer's disease

Research over the past two decades supports a shared aetiology for delusions in Alzheimer's disease (AD) and schizophrenia. Functional networks involved in salience attribution and belief evaluation have been implicated in the two conditions, and striatal D2/3 receptors are increased to a comparable extent. Executive/frontal deficits are common to both disorders and predict emergent symptoms. Putative risk genes for schizophrenia, which may modify the AD process, have been more strongly implicated in delusions than those directly linked with late-onset AD. Phenotypic correlates of delusions in AD may be dependent upon delusional subtype. Persecutory delusions occur early in the disease and are associated with neurochemical and neuropathological changes in frontostriatal circuits. In contrast, misidentification delusions are associated with greater global cognitive deficits and advanced limbic pathology. It is unclear whether the two subtypes are phenomenologically and biologically distinct or are part of a continuum, in which misidentification delusions manifest increasingly as the pathological process extends. This has treatment implications, particularly if they are found to have discrete chemical and/or pathological markers.     

Classification of psychotic symptoms in dementia sufferers

Little attention has been payed to the classification of psychotic symptoms in dementia sufferers. This article compares the etiology of delusions, visual hallucinations and delusional misidentification and examines the value of factors generated from principal components analysis as a possible classificatory system in a group of 125 patients with DSM-III-R dementia in contact with clinical services who were prospectively evaluated using standardized instruments to describe in detail individual psychotic symptoms. The assessment also included the Geriatric Mental State Schedule, the History and Aetiology Schedule and the CAMCOG. Delusions and visual hallucinations had a distinct cognitive profile as did delusions and delusional misidentification, although there was an overlap between visual hallucinations and delusional misidentification. Four factors were generated from principal components analysis. Three of these closely mirrored the 3 symptom groups delusions, visual hallucinations and delusional misidentification, although the phantom-boarder delusion was correlated with the visual hallucination factor and not delusional misidentification. The fourth factor included visual hallucinations of relatives and delusions that relatives were in the house. This factor was strongly inversely associated with emotional distress and could perhaps best be seen as a comfort phenomena. The pattern of cognitive deficits and etiological associations of each of the factors were independent of one another, supporting the notion that it is useful to consider them as separate entities.     

Correlation between a reduction in Frontal Assessment Battery scores and delusional thoughts in patients with Alzheimer's disease

Aims:  The purpose of the present study was to investigate the relationship between delusional thoughts (delusional ideation or misidentification) and frontal lobe function using the Japanese version of the Frontal Assessment Battery (FAB) bedside screening neuropsychological test in early stage Alzheimer's disease (AD) patients.
Methods:  Forty-eight probable AD patients with Mini-Mental State Examination score ≧18 points and a clinical dementia rating score of either 0.5 or 1.0 were divided into two groups based on data obtained from interviews with their caregivers: a delusional thought group ( n  = 19) and a non-delusional thought group ( n  = 29). The FAB total and subtest scores were then compared for the two groups.
Results:  Significant differences were found between the FAB total ( P  < 0.01) and subtest scores (similarities, motor series, conflicting instructions; P  < 0.05) for the two groups. Multiple regression analysis showed that delusional thought was significantly associated with the FAB total score.
Conclusions:  In addition to episodic memory disorders, a reduction in the FAB score may reflect frontal lobe dysfunctions, including executive function, in patients with AD, leading to delusional ideation.     

Behavioral profile of Alzheimer's disease in Chinese elderly--a validation study of the Chinese version of the Alzheimer's disease behavioral pathology rating scale

OBJECTIVES: This study aims to examine the psychometric properties of the Chinese version of the Alzheimer's disease behavioral pathology rating scale (CBehave-AD) and the behavioral profile of Chinese patients with AD. METHODS: Seventy-one subjects with NINCDS-ADRDA diagnosis of probable and possible AD were assessed for validation of the CBehave-AD. A behavioral symptom frequency checklist, the Chinese version of the Blessed Roth dementia scale (CDS) and the Cantonese version of the Mini-Mental State Examination (CMMSE) were used for comparison. An extended sample of 120 AD patients was then evaluated with the CBehave-AD. RESULTS: High correlations between the CBehave-AD and checklist scores were found (paranoid and delusional ideation, hallucinations, activity disturbances, aggressiveness and diurnal rhythm disturbances). The scale also demonstrated satisfactory inter-rater and test-retest reliabilities. The mean (SD) CMMSE score of the 120 patients was 9.4 (7.1). Among them, 32% have delusions, 15% had hallucinations, 54% had activity disturbances, 61% had aggressive behavior, 44% had sleep disturbance, 24% had affective disturbances, 19% had anxiety and phobias. Delusional ideation was significantly associated with hallucinations, aggressiveness, and affective disturbances. Diurnal rhythm disturbances were associated with activity disturbances and aggressiveness. CBehave-AD total scores were not significantly correlated with severity of AD, but individual symptom categories showed different pattern of correlation. Delusions, hallucinations, anxiety and phobias were significantly correlated with dementia staging. CONCLUSION: The findings suggest that the CBehave-AD is a valid assessment tool for behavioral disturbances in patients with AD. Variable associations between different symptom categories and dementia staging suggest a need for further exploration of the complex interactions between behavioral and cognitive disturbances in dementia.     

Psychotic features and the course of Alzheimer's disease: relationship to cognitive,electroencephalographic and computerized tomography findings

Thirty-one of 50 patients satisfying the NINCDS-ADRDA criteria of probable or possible Alzheimer's disease showed psychotic features during a 2-year observation period. Paranoid delusions were reported in 23 patients, delusional misidentification in 17, visual hallucinations in 16 and auditory hallucinations in 8. All of the 7 patients who died within the observation period had suffered from psychotic features even before the preterminal phase of illness. A faster progression of illness towards more severe stages of dementia was associated with paranoid delusions and hallucinations but not with delusional misidentification. We could not prove a significant influence of age, age of onset, cognitive performance, ventricular enlargement or the severity of quantitative electroencephalographic changes at initial examination on the course of illness. This may indicate that specific psychotic features and their potential organic substrate exert an effect on the progression of illness and on survival in Alzheimer's disease, which is not related to gross brain atrophy and generalized neurophysiological changes.     

Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes.

BACKGROUND: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable phenotype associated with more rapid cognitive decline. The authors have proposed that AD+P is itself a composite of a misidentification and a paranoid subtype with increased cognitive impairment restricted to the misidentification type. Most prior studies of the clinical correlates of AD+P have been limited, however, by the inclusion of prevalent cases. METHODS: Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were assessed at the time of initial presentation and then annually. Psychotic symptoms were assessed using the CERAD Behavioral Rating Scale. Survival analyses used Cox proportional hazard models with time-dependent covariates to examine the predictors of psychosis onset. RESULTS: A total of 288 subjects completed at least one follow-up examination. Mean duration of follow-up was 22.1 months. The incidence of psychosis was 0.19 per person-year. Cognitive impairment was associated with onset of psychosis, largely as a result of its association with onset of the misidentification, but not the paranoid, subtype. Including psychotropic medication use in the model revealed an association of antidepressant use with the onset of psychosis. This latter association appeared to arise from an underlying association between depression and the risk of psychosis onset rather than from antidepressant treatment. CONCLUSION: These findings are consistent with the hypothesis that the misidentification and the paranoid subtypes each define a more biologically homogeneous group than AD+P as a whole. Further exploration of the relationship between depressive symptoms and psychosis in patients with AD is warranted.     

Pathology and temporal onset of visual hallucinations,misperceptions and family misidentification distinguishes dementia with Lewy bodies from Alzheimer's disease

ObjectiveTo determine whether the temporal onset of visual phenomena distinguishes Lewy body disease (LBD) from Alzheimer's disease (AD), and to characterize the extent Lewy bodies and neurofibrillary tangles are associated with these clinical features.MethodsConsecutive cases of autopsy-confirmed LBD (n = 41), AD (n = 70), and AD with amygdala-predominant Lewy bodies (AD-ALB) (n = 14) with a documented clinical history of dementia were included. We mailed questionnaires to next-of-kin asking about symptoms during life. Lewy pathology and neurofibrillary tangle pathology were assessed.ResultsThe occurrence of visual hallucinations, misperceptions and family misidentification did not distinguish LBD from AD or AD-ALB, but the onset was earlier in LBD compared to AD and AD-ALB. When visual hallucinations developed within the first 5 years of dementia, the odds were 4–5 times greater for autopsy-confirmed LBD (or intermediate/high likelihood dementia with Lewy bodies) and not AD or AD-ALB. In LBD, limbic but not cortical Lewy body pathology was related to an earlier onset of visual hallucinations, while limbic and cortical Lewy body pathology were associated with visual misperceptions and misidentification. Cortical neurofibrillary tangle burden was associated with an earlier onset of misidentification and misperceptions in LBD and AD, but only with earlier visual hallucinations in AD/AD-ALB.ConclusionWhen visual hallucinations occur within the first 5 years of the dementia, a diagnosis of LBD was more likely than AD. Visual hallucinations in LBD were associated with limbic Lewy body pathology. Visual misperceptions and misidentification delusions were related to cortical Lewy body and neurofibrillary tangle burden in LBD and AD/AD-ALB.     

Right parietal activation during delusional state in episodic interictal psychosis of epilepsy: a report of two cases

Magnetoencephalography (MEG) was used to image brain activity associated with delusions in episodic interictal psychosis of epilepsy. Two female patients aged 65 and 68 with temporal lobe epilepsy were studied during and after a delusional state. Topographic images of the excess kurtosis (g2), the statistical index of spikelike activity, were obtained from unaveraged MEG recordings using an analysis called "synthetic aperture magnetometry" (SAM). For both patients, MEG waveforms and excess kurtosis images revealed spiky activity in the right inferior parietal region during the delusional state. A second MEG measurement after delusions were resolved with antipsychotic therapy revealed no excess kurtosis in the right parietal area. Likewise, the sharp waves on MEG recordings disappeared as well. Our results suggest association of the right inferior parietal cortex, including the supramarginal gyrus, with the delusional state of episodic interictal psychosis of epilepsy.     

Neuropsychiatric symptoms in the dementias

PURPOSE OF REVIEW: Neuropsychiatric, or non-cognitive symptoms are increasingly recognized as manifestations of dementias. RECENT FINDINGS: In Alzheimer's disease, recent advances have included the identification of behavioral profiles, differentiation of apathy and depression, characterization of risk factors for psychosis and its links to agitation and aggression, and an analysis of depressive symptoms in the absence of major depression. Functional neuroimaging data mainly supported the role of the anterior cingulate in apathy. The orbitofrontal and anterior cingulate tangle burden were associated with agitation, and increased orbitofrontal and mid-temporal muscarinic M2 receptors with psychosis and hallucinations. Selected genetic polymorphisms of dopamine and serotonin receptors or transporters were linked with aggression, hallucinations or psychosis. When compared with other dementias, individuals with frontotemporal dementia disclosed, as expected, different behaviors and particularly aberrant social behavior. The frequency of delusions and visual hallucinations was increased in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies, suggesting common mechanisms such as Lewy body pathology and cholinergic deficiency. The latter was supported by an improvement of these symptoms by cholinesterase inhibitors. SUMMARY: Future research directions include both clinical and basic neuroscience investigations. The detection of early neuropsychiatric symptoms might be a marker for dementia, and the possible existence of a mild neuropsychiatric impairment syndrome should be explored. More longitudinal studies with pathological confirmation will facilitate correlations with neuropsychiatric symptoms. Functional neuroimaging and behavioral neurogenetics will permit in-vivo correlations and consequently help patient management and care.     

Delusions in dementia syndromes: investigation of behavioral and neuropsychological correlates.

A prospective cross-sectional investigation examining the relationship of neuropsychological and behavioral changes to the occurrence of delusions in dementia syndromes was conducted. Nineteen patients had Alzheimer's disease (AD), and 14 had multi-infarct dementia (MID). Patients with and without delusions were compared with regard to demographic characteristics, neuropsychological and neurological features, and a variety of behavioral disturbances. Delusional patients were more aggressive and exhibited more severe activity disturbances than nondelusional patients. Delusional patients were more severely cognitively impaired, but the neuropsychological differences between the two groups were not outstanding. These observations suggest that specific neuropsychological deficits are not compelling predictors of delusions and that delusional patients are more behaviorally disturbed than those without delusions. It is hypothesized that delusions are independent noncognitive manifestations of the neurobiology of AD and MID.