Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003

OBJECTIVE: The authors reviewed studies published between 1990 and 2003 that reported the prevalence, incidence, and persistence of, as well as the risk factors associated with, psychosis of Alzheimer's disease. METHOD: PubMed and PsycINFO databases were searched by using the terms "psychosis and Alzheimer disease" and "psychosis and dementia." Empirical investigations presenting quantitative data on the epidemiology of and/or risk factors for psychotic symptoms in Alzheimer's disease were included in the review. A total of 55 studies, including a total of 9,749 subjects, met the inclusion criteria. RESULTS: Psychosis was reported in 41% of patients with Alzheimer's disease, including delusions in 36% and hallucinations in 18%. The incidence of psychosis increased progressively over the first 3 years of observation, after which the incidence seemed to plateau. Psychotic symptoms tended to last for several months but became less prominent after 1 year. African American or black ethnicity and more severe cognitive impairment were associated with a higher rate of psychosis. Psychosis was also associated with more rapid cognitive decline. Some studies found a significant association between psychosis and age, age at onset of Alzheimer's disease, and illness duration. Gender, education, and family history of dementia or psychiatric illness showed weak or inconsistent relationships with psychosis. CONCLUSIONS: Psychotic symptoms are common and persistent in patients with Alzheimer's disease. Improved methods have advanced the understanding of psychosis in Alzheimer's disease, although continued research, particularly longitudinal studies, may unveil biological and clinical associations that will inform treatments for these problematic psychological disturbances.     

The neurobiology of neuropsychiatric syndromes in dementia

PURPOSE OF REVIEW: Neuropsychiatric disturbances in dementia are prevalent, and research is uncovering their neurobiological correlates. RECENT FINDINGS: Late-onset depression appears to be associated with Alzheimer's disease pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for both late-onset depression and Alzheimer's disease and may partly mediate their relationship. Monoamine changes are robust finding in Alzheimer's disease and may account for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to be increased by several genes also implicated in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian sleep-wake cycles, including decreased night-time melatonin. Sleep apnea may be related to apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement sleep behavior disorder is intricately related to synucleinopathies, such as dementia with Lewy bodies, but synuclein changes may not totally explain this relationship. SUMMARY: Neuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.     

Diabetes mellitus and the risk of dementia,Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging

BACKGROUND: Conflicting results have been reported about the status of diabetes mellitus as a risk for Alzheimer's disease. We investigated the relationship between diabetes and incident dementia (including Alzheimer's disease and vascular cognitive impairment) in a 5-year longitudinal study. METHODS: Secondary analysis of the Canadian Study of Health and Aging, a representative cohort study of dementia in older Canadians. RESULTS: 5,574 subjects without cognitive impairment at baseline participated in 5-year follow-up. Diabetes mellitus at baseline was associated with incident vascular cognitive impairment (RR: 1.62; 95% CI: 1.12-2.33) and its subtypes, vascular dementia (RR: 2.03; 95% CI: 1.15-3.57), and vascular cognitive impairment not dementia (RR: 1.68; 95% CI: 1.01-2.78). Diabetes was not associated with mixed Alzheimer's/vascular dementia (RR: 0.87; 95% CI: 0.34-2.21), incident Alzheimer's disease (RR: 1.30; 95% CI: 0.83-2.03) or all dementias (RR: 1.26; 95% CI: 0.90-1.76). CONCLUSIONS: Despite increased recognition of the role of vascular factors in Alzheimer's disease, we did not find an association between diabetes and incident Alzheimer's disease, even though diabetes was associated with incident vascular cognitive impairment.     

Cognitive and behavioural impairment in Parkinson's disease

Although Parkinson's disease (PD) has been considered to primarily affect motor abilities, increasing emphasis is being placed on cognitive and behavioural impairment in this disorder. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both patients and families. This article reviews cognitive and behavioural disturbances in PD and their relation to affective and motor symptoms, treatment of dementia associated with PD, and treatment approaches to psychosis in PD. We also discuss similarities between the dementia of PD and dementia with Lewy bodies.     

Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease

BACKGROUND: The relation between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unknown. OBJECTIVES: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer's disease). DESIGN: Survey of cognitive features. SETTING: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. PATIENTS: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer's disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. MAIN OUTCOME MEASURES: Dementia rating scale subscores corrected for age. RESULTS: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer's disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). CONCLUSIONS: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer's disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer's disease.     

Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the cardiovascular health study

OBJECTIVE The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. METHOD The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. RESULTS The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. CONCLUSIONS Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.     

Syndromic validity of apathy in Alzheimer's disease

OBJECTIVE: The study examined the usefulness and clinical correlates of specific diagnostic criteria for apathy in Alzheimer's disease. Whereas apathy is a frequent behavioral change in patients with Alzheimer's disease, the lack of standardized diagnostic criteria may explain the wide discrepancies in estimates of the frequency and demographic and clinical correlates of apathy. METHOD: A consecutive series of 319 patients who met the criteria for probable Alzheimer's disease established by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, 117 patients who met the DSM-IV criteria for depression without dementia, and 36 healthy individuals were assessed with a structured psychiatric interview. On the basis of modified Marin's criteria for apathy, they were classified into groups with or without apathy. RESULTS: Apathy was diagnosed in 37% of the 319 Alzheimer's disease patients, compared to none of the healthy comparison subjects. In 24% of the Alzheimer's disease sample, apathy coexisted with either dysthymic disorder or major depressive disorder, whereas 13% had apathy without depression. Apathy was diagnosed in 32% of the depressed nondemented patients, mostly in those with major depressive disorder. Apathy in Alzheimer's disease was significantly associated with severe impairments in activities of daily living and cognitive functions, older age, and poor awareness of behavioral and cognitive changes. CONCLUSIONS: This study provides partial validation of specific clinical criteria for apathy in Alzheimer's disease.     

Cognitive impairment: assessment with brain magnetic resonance imaging and proton magnetic resonance spectroscopy

BACKGROUND: In vivo proton magnetic resonance spectroscopy is a safe and noninvasive tool that can be used to study aspects of brain chemistry and metabolism. This study was designed to evaluate its role in routine application to reveal the diagnostic reasons for cognitive impairment. METHOD: 37 Alzheimer's disease patients (NINCDS-ADRDA criteria), 31 patients with subcortical ischemic vascular dementia (Chui et al. criteria), and 13 subjects with subjective cognitive impairment (DSM-IV criteria) were included in this retrospective study. Magnetic resonance images were used for atrophy rating; additionally, proton magnetic resonance spectroscopy was performed. RESULTS: Significantly reduced N-acetylaspartate levels (p <.05) were found in both patients with Alzheimer's disease and patients with subcortical ischemic vascular dementia compared to the group with subjective memory complaints. The ratios of N-acetylaspartate/creatine and N-acetylaspartate/myo-inositol were significantly lower in Alzheimer's disease patients compared to patients with vascular dementia (p =.012) or patients with subjective memory impairment (p =.002). N-acetylaspartate/creatine and N-acetylaspartate/myo-inositol ratios were positively correlated to the degree of cerebral atrophy. Disoriented patients displayed a low N-acetylaspartate/creatine ratio. In contrast, we were not able to relate concurrent psychotic or behavioral symptoms to any spectroscopic parameter. CONCLUSION: This study indicates that proton magnetic resonance spectroscopy parameters could provide additional information in differentiating between Alzheimer's disease, subcortical ischemic vascular dementia, and subjective cognitive impairment. Therefore, this method can contribute to the routine diagnosis of dementia. Psychiatric and behavioral symptoms associated with dementia or due to a major psychiatric disorder cannot be related to changes in the measured proton magnetic resonance spectroscopy parameters.     

Dementia and cognitive impairment in Parkinson disease

Changes in cognitive function and disturbances in behavior are commonly seen in parkinsonian patients and they are inherent features of the disease. Estimates on the prevalence of dementia in this disorder are quite variable, ranging from 15 to 25%. Advanced age, depression, severity of akinesia, and the presence of dopaminomimetic psychosis, are considered as risk factors in the development of cognitive deterioration within this patient population. Cognitive dysfunction may manifest as relatively circumscribed deficits or overt dementia. The finding of mild cognitive deficits is common in Parkinson's disease, such as reduced flexibility, psychomotor slowing, reduction in learning capacity and information retrieval, and disturbances in visuospatial tasks. The most prevalent cognitive disturbance is an impairment in visuospatial tasks, not necessarily related to the degree of motor disability. Dementia, when present early on in the course of the disease may suggest alternative diagnoses (Diffuse Lewy body dementia, Alzheimer's disease with extrapyramidal features, Fronto-temporal dementia, etc.), while in those cases in whom the dementing disorder develops at a later stage, it is assumed to be an integral part of the disease, albeit corresponding to variable pathogenetic mechanisms.     

In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer's disease

PURPOSE: Prior proton magnetic resonance spectroscopy (MRS) studies have consistently reported decreased brain n-acetyl aspartate (NAA) levels and increased myo-inositol (mI) levels in subjects with Alzheimer's disease (AD) relative to healthy comparison subjects. These studies have usually been conducted in small and homogeneous populations of patients with established Alzheimer's disease. Few studies have tested the usefulness of this finding in a general population seeking evaluation for memory loss and other cognitive declines. We designed a study to evaluate the significance of single-voxel proton MRS findings in these patients with memory loss and other cognitive declines. GENERAL METHOD: Thirty-five subjects with a primary complaint of memory loss and other cognitive declines were consecutively referred over a period of 13 months to a specialty clinic. Patients with a diagnosis of mild to moderate probable Alzheimer's disease (N = 22), non-Alzheimer's dementia (depression, multiinfarct dementia, Parkinson's Disease, Korsakoff's Psychosis, and bipolar disorder; N = 13), and healthy comparison subjects (N = 18) were examined with respect to possible differences in metabolites using proton MRS in a 3.4-ml anterior temporal lobe voxel. FINDINGS: The Alzheimer's disease group had 10.7% lower NAA/creatine (Cr) ratios relative to the healthy comparison group and 9.4% lower NAA/creatine relative to the non-Alzheimer's dementia group (15.0% lower NAA/creatine relative to the depression subgroup of the non-Alzheimer's dementia group). There were no significant differences in choline (Cho) or myo-inositol ratios among the groups. There were significant correlations between NAA/creatine ratios and mini-mental status exam (MMSE) scores in subjects with Alzheimer's disease (t = 2.41, p = 0.032) but not in subjects with non-Alzheimer's dementia or in its depression subgroup. CONCLUSIONS: This study found a reduction in the neuronal marker NAA in the anterior temporal lobe of patients diagnosed with probable Alzheimer's disease, using a short add-on proton MRS exam. This change was not observed in patients whose memory loss and other cognitive declines were not attributed to Alzheimer's disease, suggesting that it may aid in the diagnosis or detection of Alzheimer's disease.     

Cognitive and behavioural impairment in Parkinson's disease

Although Parkinson's disease (PD) has been considered to primarily affect motor abilities, increasing emphasis is being placed on cognitive and behavioural impairment in this disorder. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both patients and families. This article reviews cognitive and behavioural disturbances in PD and their relation to affective and motor symptoms, treatment of dementia associated with PD, and treatment approaches to psychosis in PD. We also discuss similarities between the dementia of PD and dementia with Lewy bodies.     

Factors associated with psychotic symptoms in Alzheimer's disease

OBJECTIVES—Many clinical and biological factorshave been reported to be associated with the presence of psychosis inpatients with Alzheimer's disease, although the associations werevariable. The aim of this study was to clarify factors associated withthe presence of psychosis in patients with Alzheimer's disease.
METHODS—Psychiatric functioning was studied in 228 patients with Alzheimer's disease based on the results of thebehavioural pathology in Alzheimer's disease rating scale or theneuropsychiatric inventory. The effects of sex, education level, age,duration of illness, cognitive function, and apolipoprotein E genotypewere investigated for dichotomous psychotic status with a multiplelogistic regression analysis.
RESULTS—Of the 228 patients with Alzheimer'sdisease, 118 (51.8%) showed evidence of delusions or hallucinations.Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and moresevere cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was notsignificantly related to either educational level or apolipoprotein E genotype.
CONCLUSIONS—Age, sex, and severity of illness wereindependent factors associated with the presence of psychosis inpatients with Alzheimer's disease. The reason why some patients withAlzheimer's disease develop psychosis remains unclear. There may bedistinctive subtypes of Alzheimer's disease or the presence ofindividual factors which affect the development of psychosis.

     

Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies. CONCLUSIONS: The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.     

Worsening of post-traumatic stress disorder symptoms with cognitive decline: case series

We present three cases of post-traumatic stress disorder (PTSD) symptoms associated with cognitive decline. Patient age ranged from 57 to 70 years old and all patients had war-related PTSD. In each case, the patient had a history of PTSD that was under fairly good control until the onset of cognitive impairment due to Alzheimer's disease or vascular or alcohol-related dementia. These cases suggest that neurodegeneration of memory pathways may disinhibit symptoms of PTSD.     

Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease

Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.     

Education,occupation, and prevalence of dementia: findings from the Conselice study

Information about the epidemiology of dementia in Italy is still limited, although this cognitive disorder represents a serious public health concern. We estimated the prevalence of dementia and dementia subtypes in the elderly population of a Northern Italian municipality, Conselice, in the Emilia Romagna region (n = 1,016 subjects aged 65-97 years). The associations of dementia with two modifiable risk factors, education and occupation, were also evaluated. Overall dementia prevalence was 5.9% (95% confidence interval 4.3-7.8), exponentially increased with age, and was higher among women. Of the dementia cases, 50% were Alzheimer's disease (AD), but an unusually high prevalence (45%) was found for vascular dementia (VD). After adjustment for age and gender, education but not occupation was associated with both AD and VD. This association could not be explained by occupation, life habits, and previous history of hypertension or cardiovascular disease.     

Non-cognitive symptoms in mild cognitive impairment subjects

The term mild cognitive impairment (MCI) is used to identify individuals with worse cognitive performance than those with normal aging, and who are at risk of dementia, especially Alzheimer's disease (AD). Although the MCI concept is based on the presence of specific cognitive deficits, several studies have shown that these subjects can develop depression, disruptive behaviors (e.g., agitation, aggression), and psychosis. In this study, we examined the baseline psychiatric characteristics of 228 MCI (Mean age: 71.2, Mini-mental State Examination [MMSE] score: 25.9) and 427 mildly demented Probable AD (Mean age: 73.2; Mean MMSE score: 23.5) subjects from a referral dementia clinic. The psychiatric assessment was conducted by geriatric psychiatrists using semi-structured interviews. The proportion of subjects with major depression (MCI: 7.5% vs. Probable AD: 8%) and aggression (MCI: 10% vs. Probable AD: 12.5%) was similar in the two groups. There were more Probable AD patients with psychomotor agitation (52% vs. 38%), delusions (29% vs. 14%), and hallucinations (9% vs. 4%) than MCI subjects. Within MCI groups, we did not observe any differences between MCI subjects with amnesic syndrome versus MCI subjects with a much broader cognitive deficit. These results showed that the MCI syndrome is not circumscribed to a neuropsychological definition, but occurs with a wide range of psychiatric syndromes. Furthermore, it is possible that the development of disruptive behaviors and psychosis, in MCI subjects with no previous history of psychiatric illness, constitutes a strong indication that there is an underlying neurodegenerative disorder.     

REM sleep behavior disorder and dementia: cognitive differences when compared with AD

OBJECTIVE: To determine whether the dementia associated with REM sleep behavior disorder (RBD) differs from Alzheimer's disease (AD) and, if so, whether differences in cognitive performance between RBD/dementia and AD resemble reported differences between dementia with Lewy bodies (DLB) and AD. METHODS: This retrospective study compares neurocognitive performance between 31 patients with degenerative dementia and polysomnography-confirmed RBD and 31 patients without brainstem Lewy body pathology who met Consortium to Establish a Registry for Alzheimer's Disease (CERAD) clinical and neuropathologic criteria for AD. The patient groups did not differ in dementia severity (based on Global Deterioration Scale score) or duration. RESULTS: RBD preceded or coincided with the onset of cognitive decline in 94% of the patients. All but one patient with RBD/dementia had one or more of the following clinical features of DLB: visual hallucinations, extrapyramidal signs, or fluctuating cognition/alertness. The data revealed significantly worse performance on attention, perceptual organization, visual memory, and letter fluency for the RBD/dementia group, whereas the AD group showed significantly worse performance on confrontation naming and verbal memory. CONCLUSIONS: Patients with RBD and degenerative dementia demonstrate a significantly different pattern of cognitive performance from patients with AD. Most of the patients in the RBD/dementia sample also meet criteria for possible or probable DLB, and the pattern of cognitive differences from AD is similar to reported comparisons between DLB and AD. The cognitive and clinical data provide evidence to suggest that the dementia associated with RBD may represent DLB.     

Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease

This cross-sectional study examines relationships among the constellation of psychiatric syndromes in Alzheimer's disease (AD) as a function of dementia severity in 1155 patients with probable AD. The frequency of major depression decreased in severe stages, while agitation, aggression, and psychosis were more frequent in late stages. Major depression was associated with anhedonia, sleep disorders, depressed mood, low self-esteem, anxiety, and hopelessness in mild/moderate and severe stages. Agitation was associated with aggression and psychosis in mild/moderate stages, and psychosis was associated with aggression in moderate/severe stages. In addition, there was a constellation of psychiatric symptoms (e.g., anxiety, wandering, irritability, inappropriate behavior, uncooperativeness, emotional lability) associated with agitation, aggression, and psychosis, which varied according to the severity of the dementia, suggesting a progressive deterioration of frontal-temporal limbic structures. Education and race were independently associated with psychosis. However, while education was associated with psychosis in mild/moderate stages, race was associated with psychosis in moderate/severe stages.