An observer-rated strategy for differentiating schizophrenic and manic states in inpatient settings.

OBJECTIVES: Differentiating schizophrenia from mania in acutely psychotic patients can be difficult, but is important in determining immediate and subsequent management. Such differentiation is generally addressed by clinical interviews, but an observational approach may assist. This paper therefore describes the development of a relevant observational measure. METHODS: We developed a provisional list of 49 items (weighting features with suggested specificity to schizophrenia and mania) for independent completion by two nurses and judged its ability to predict diagnosis provided by consultant psychiatrists. RESULTS: Eighty-seven psychotic patients were recruited, and 173 completed data sets were analysed. We refined the item set to two sets of 10 items that best-differentiated schizophrenia from mania and vice versa. Optimal differentiation was achieved with a score of at least 7 on both the schizophrenia and mania item sets. Difference scores (i.e. schizophrenia items affirmed minus mania items affirmed) were also generated, with a difference score of +1 (i.e. one or more schizophrenia items being affirmed than mania items) showing optimal differentiation (sensitivity 0.67, specificity 0.82) between the two conditions. Evaluating all potential difference scores, we demonstrated that, as difference scores increased, diagnostic accuracy in identifying each condition was very high. CONCLUSION: Analyses allow the properties of an observational measure (the 20-item Sydney Psychosis Observation Tool) to be described. While a single cut-off difference score was derived with acceptable discriminatory ability, we also established the capacity of varying difference scores to assign both schizophrenia and mania diagnoses with high accuracy.

Apathy and Depression in Huntington's Disease: Distinct Longitudinal Trajectories and Clinical Correlates.

OBJECTIVE: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease resulting in motor disturbances, dementia, and psychiatric symptoms. Apathy is a common manifestation and rated as one of the most impactful by patients and caregivers. It can often be difficult to distinguish from depression because of shared features and frequent overlap. This study examined the longitudinal trajectories and clinical correlates of apathy and depression. METHODS: Data were drawn from the Cooperative Huntington Observational Research Trial, a prospective, multicenter observational study that recruited 1,082 patients with HD. Measures of cognition, function, neuropsychiatric symptoms, motor function, and medication use were completed annually over 5 years. RESULTS: Overall, 423 patients (39%) showed evidence of apathy at study baseline, and both the prevalence and overall severity of apathy increased over time. Depression, by contrast, affected a similar proportion at baseline, although levels remained relatively stable over the study. Apathy was associated with worse cognition, function, neuropsychiatric symptoms, and motor symptoms. Depression was associated with worse neuropsychiatric symptoms, suicidal ideation, and independence but not other outcomes after control for other variables. CONCLUSIONS: Apathy in HD increased over time and was associated with worse clinical outcomes. These associations were independent of depression and other clinical variables. The findings highlight the need to distinguish between apathy and depression given their distinct implications for prognosis and management.

Apathy and depression in mild cognitive impairment: distinct longitudinal trajectories and clinical outcomes.

OBJECTIVES: Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues. DESIGN: A prospective longitudinal study was conducted over 3 years. SETTING: Nine memory clinics around Australia. PARTICIPANTS: One hundred and eighty-five patients with MCI at baseline. MEASUREMENTS: Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points. RESULTS: Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms. CONCLUSIONS: Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

Distinguishing apathy and depression in dementia: A longitudinal study.

OBJECTIVES: Apathy is a common symptom in dementia, though can be difficult to distinguish from depression due to shared features and frequent co-occurrence. As such, a significant limitation of much previous research on apathy is the failure to control for depression. The current study sought to address this by examining the trajectory and clinical correlates of apathy after controlling for depression. METHODS: Seven hundred and seventy-nine patients with dementia were recruited from nine memory clinics around Australia. Measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden and medication use were completed at baseline and at regular intervals over a 3-year period. Driving and institutionalisation data were obtained throughout the study. Mortality data were obtained from state registries 8 years after baseline. RESULTS: Of the 662 patients with completed measures of neuropsychiatric symptoms, 342 (51.7%) had apathy and 332 (50.2%) had depression at baseline, while 212 (32.0%) had both. Whereas apathy increased over time, depression remained relatively stable. Apathy, but not depression, was associated with greater dementia severity, poorer cognition and function, driving cessation and mortality. Both apathy and depression were associated with greater neuropsychiatric symptoms, psychosis, caregiver burden and institutionalisation. CONCLUSIONS: Apathy increases over the course of dementia and is associated with worse clinical outcomes independent of depression. Distinguishing apathy and depression appears important given their different implications for prognosis and management.

Paediatric bipolar disorder and its controversy.

OBJECTIVES: Paediatric bipolar disorder - bipolar disorder occurring in prepubertal children - is a diagnosis subject to considerable controversy. Whilst historically considered to be very rare, proponents since the 1990s have argued that mania can present differently in children and, as such, is much more common than previously thought. Such proposals raise questions about the validity of proposed phenotypes and potential risks of iatrogenic harm. METHODS: I critically examine the construct of paediatric bipolar disorder using Robins and Guze's (1970, American Journal of Psychiatry126, 983-987) influential criteria for the validity of a psychiatric diagnosis. I review, in turn, evidence relating to its clinical description, delimitation from other conditions, follow-up studies, family studies, laboratory studies, and treatment response. RESULTS: Across domains, existing research highlights significant challenges establishing the diagnosis. This includes significant heterogeneity in operationalising criteria for children; variable or poor inter-rater reliability; difficulty distinguishing paediatric bipolar disorder from other conditions; large differences in rates of diagnosis between the United States of America and other countries; limited evidence of continuity with adult forms; and a lack of evidence for proposed paediatric phenotypes in children at genetic high-risk of the condition. Laboratory and treatment studies are limited, but also do not provide support for the construct. CONCLUSIONS: Evidence for the more widespread existence of paediatric bipolar disorder and its various proposed phenotypes remains weak. The ongoing popularity of the diagnosis, most evident in America, may reflect social pressures and broader limitations in psychiatric nosology. The uncertainty around the diagnosis highlights the need for careful longitudinal assessment of children potentially affected.

Psychosis and longitudinal outcomes in Huntington disease: the COHORT Study.

OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disease involving motor disturbances, cognitive decline and psychiatric symptoms. Psychotic symptoms occur in a significant proportion of patients. We sought to characterise the clinical outcomes of this group of patients. METHODS: Data were drawn from the Cooperative Huntington Observational Research Trial, a prospective, multi-centre observational study. 1082 patients with HD were recruited. Measures of cognition, function, behavioural disturbance and motor function were completed annually over 5 years. RESULTS: Overall, 190 patients (17.6%) displayed psychotic symptoms. These patients demonstrated worse cognition, function and behavioural disturbances than patients without psychosis over time. Patients with psychosis also demonstrated lower levels of chorea than patients without psychosis, despite adjusting for concurrent antipsychotic and tetrabenazine use. CONCLUSIONS: Psychosis in HD is associated with poorer outcomes in cognition, function and behavioural symptoms. Patients with psychotic symptoms may also have less chorea. Altogether, the findings suggest patients with psychosis have a distinct clinical course.

Dementia and caregiver burden: A three-year longitudinal study.

OBJECTIVES: Dementia, with its progressive cognitive and functional decline and associated neuropsychiatric symptoms, places a large burden on caregivers. While frequently studied, longitudinal findings about the overall trajectory of burden are mixed. The study sought to characterize caregiver burden over a 3-year period and identify predictors of this burden. METHODS: Seven-hundred-and-eighty-one patients with dementia were recruited from nine memory clinics around Australia. Measures of caregiver burden, cognition, function, and neuropsychiatric symptoms were completed with patients and their caregivers at regular intervals over a 3-year period. Patients' level of services and medication use were also recorded. RESULTS: Of the 720 patients with measures of caregiver burden at baseline, 47.4% of caregivers had clinically significant levels of burden. This proportion increased over time, with 56.8% affected at 3 years. Overall levels of burden increased for caregivers of patients without services, though did not change for caregivers of patients receiving services or residential care after controlling for other variables. Patient characteristics-including greater neuropsychiatric symptoms, lower functional ability, fewer medications, lack of driving ability-and female sex of caregivers were associated with greater burden. CONCLUSIONS: High levels of caregiver burden are present in a large proportion of caregivers of people with dementia and this increases over time for those without services. Clinical characteristics of patients (including neuropsychiatric symptoms, function, overall health, driving status), level of services, and caregiver sex appear to be the best predictors of this burden. These characteristics may help identify caregivers at greater risk of burden to target for intervention.

Delusions and theories of belief.

Cognitive neuropsychiatry is a branch of cognitive psychology that seeks to explain neuropsychiatric symptoms in terms of disruptions or damage to normal cognitive processes. A key objective of this approach is to use insights derived from the study of pathological symptoms to inform accounts of premorbid cognitive systems. Delusions, in particular, can be considered to represent dysfunction of the cognitive processes underlying belief formation, so studying delusions may provide unique insights into nonpathological belief. While this approach has provided compelling accounts for a range of delusions in terms of putative cognitive dysfunctions, it is less clear that it has achieved progress in its reciprocal goal of informing understanding of belief more generally. In this review, we trace the origins of the cognitive neuropsychiatric approach and consider the reasons for the lack of progress. We propose a tentative framework to overcome these challenges and suggest directions for future research.

Longitudinal outcomes of patients with pseudodementia: a systematic review.

Depression and a number of other psychiatric conditions can impair cognition and give the appearance of neurodegenerative disease. Collectively, this group of disorders is known as 'pseudodementia' and are important to identify given their potential reversibility with treatment. Despite considerable interest historically, the longitudinal outcomes of patients with pseudodementia remain unclear. We conducted a systematic review of longitudinal studies of pseudodementia. Bibliographic databases were searched using a wide range of search terms. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 18 studies with follow-up varying from several weeks to 18 years. Overall, 284 patients were studied, including 238 patients with depression, 18 with conversion disorder, 14 with psychosis, and 11 with bipolar disorder. Irrespective of diagnosis, 33% developed irreversible dementia at follow-up, 53% no longer met criteria for dementia, and 15% were lost to follow-up. Considerable variability was identified, with younger age at baseline, but not follow-up duration, associated with better outcomes. ECT and pharmacological interventions were also reported to be beneficial, though findings were limited by the poor quality of the studies. Overall, the findings suggest that pseudodementia may confer an increased risk of irreversible dementia in older patients. The findings also indicate, however, that a significant proportion improve, while many remain burdened with their psychiatric condition, independent of organic dementia. The findings support the clinical value of the construct and the need for its re-examination in light of developments in neuroimaging, genomics, other investigative tools, and trial methodology.

Mild Cognitive Impairment and Caregiver Burden: A 3-Year-Longitudinal Study.

OBJECTIVES: Mild cognitive impairment (MCI) is common, affecting 10%-35% of people over 65, and poses unique challenges for patients and their caregivers. Comparatively little research has examined caregiver burden in this population, with longitudinal research, in particular, lacking. We examined caregiver burden in a sample of people with MCI over 3 years. DESIGN: Three-year observational study. SETTING: Nine memory clinics in Australia. PARTICIPANTS: One-hundred-and-eighty-five people with MCI and their caregivers. MEASUREMENTS: Measures of caregiver burden, cognition, function, neuropsychiatric symptoms, driving status, and medication use were completed with patients and their caregivers at regular intervals over a 3-year period. RESULTS: Between 21.1% and 29.5% of caregivers reported a clinically significant level of burden over the study. Patients' higher levels of neuropsychiatric symptoms, lower functional ability, and lack of driving ability, and caregivers' employment were associated with greater caregiver burden over time. Caregiver burden did not increase over time when controlling for patient and caregiver characteristics. CONCLUSIONS: High levels of caregiver burden are present in a significant proportion of caregivers of people with MCI. Clinical characteristics of patients - including severity of neuropsychiatric symptoms and functional impairment - and the employment status of caregivers predict burden. Such characteristics may help identify caregivers at greater risk of burden to target for intervention.

Non-pharmacological interventions for Lewy body dementia: a systematic review.

Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.

Psychosis and Clinical Outcomes in Alzheimer Disease: A Longitudinal Study.

OBJECTIVE: Psychotic symptoms are a common feature in Alzheimer disease (AD), occurring in approximately 40% of patients. These symptoms are associated with worse clinical outcomes. Comparatively little research, however, has distinguished delusions and hallucinations, which may have distinct clinical, neuropathological, and genetic correlates. To address this, the current study examined the clinical outcomes associated with delusions and hallucinations in AD. DESIGN: Three-year observational study. SETTING: Nine memory clinics in Australia. PARTICIPANTS: A total of 445 patients with AD. MEASUREMENTS: Measures of neuropsychiatric symptoms, dementia severity, cognition, function, caregiver burden, and medication use were completed annually for 3 years with additional assessments at 3 months and 6 months in the first year. Mortality data were obtained from state registries approximately 5 years after the study. RESULTS: Of 445 patients, 102 (22.9%) developed only delusions, 39 (8.8%) developed only hallucinations, and 84 (18.9%) developed both symptoms. Delusions and hallucinations were both associated with greater dementia severity, poorer cognition and function, higher levels of other neuropsychiatric symptoms, and greater caregiver burden. The presence of both symptoms was associated with worse outcomes than only one of these symptoms. Delusions, both by themselves and in combination with hallucinations, predicted institutionalization. Antipsychotic medication use predicted mortality. CONCLUSIONS: Delusions and hallucinations independently and in combination are associated with poor clinical outcomes. The findings highlight the challenges managing these patients, particularly given the high levels of caregiver burden associated with psychotic symptoms and the likely mortality arising from antipsychotic medication.

Proportional hazard model estimation under dependent censoring using copulas and penalized likelihood.

This paper considers Cox proportional hazard models estimation under informative right censored data using maximum penalized likelihood, where dependence between censoring and event times are modelled by a copula function and a roughness penalty function is used to restrain the baseline hazard as a smooth function. Since the baseline hazard is nonnegative, we propose a special algorithm where each iteration involves updating regression coefficients by the Newton algorithm and baseline hazard by the multiplicative iterative algorithm. The asymptotic properties for both regression coefficients and baseline hazard estimates are developed. The simulation study investigates the performance of our method and also compares it with an existing maximum likelihood method. We apply the proposed method to a dementia patients dataset.

Predictors of Driving Cessation in Dementia: Baseline Characteristics and Trajectories of Disease Progression.

A diagnosis of dementia implies the eventual need to relinquish driving. This is associated with significant morbidity and anticipating when it will need to occur can be important for planning. Patients, however, vary in the course of their disease. We sought to identify predictors of driving cessation in patients with dementia, including both baseline characteristics and changes in cognition and function over time as indicators of disease trajectory. A total of 779 patients with dementia were recruited from 9 memory clinics around Australia. Patients and their carers reported their driving status and completed measures of dementia severity, cognition, function, neuropsychiatric symptoms, and medication use at regular intervals over a 3-year period. Of the 247 patients still driving at baseline, 147 (59.5%) stopped driving during the study. Variables that predicted driving cessation included older age; female sex; greater dementia severity and cognitive and functional impairments at baseline; and greater increases in dementia severity and cognitive and functional impairments over 3 and 6 month periods. The findings confirm that easily assessable characteristics, including changes over time, predict future driving status. The findings underscore the value of regularly assessing patients with standardized measures to determine disease trajectory and likely prognosis.

The stability of neuropsychiatric subsyndromes in Alzheimer's disease.

INTRODUCTION: Neuropsychiatric symptoms are common in Alzheimer's disease. Previous research has attempted to identify subsyndromes-sets of symptoms related to one another-to clarify underlying mechanisms and treatment targets. We examined the stability of these subsyndromes over time. METHODS: We administered the Neuropsychiatric Inventory annually for 3 years to 447 patients with Alzheimer's disease recruited from memory clinics. We conducted principal component analyses at each time point and multiple-group confirmatory factor analyses across time. RESULTS: Principal component analyses showed that no two time points shared the same factor structure. Factor solutions did not exhibit strong simple structures and substantial cross-loadings were common. Confirmatory analysis revealed significant differences in factor loadings and model fit over time. DISCUSSION: Symptoms cannot be neatly partitioned into discrete clusters that are stable over time. The findings highlight the significant challenges that clinicians and caregivers face and may help explain the lack of success in intervention studies.

Mild Cognitive Impairment and Driving Cessation: A 3-Year Longitudinal Study.

BACKGROUND/AIMS: Driving cessation is associated with significant morbidity in older people. People with mild cognitive impairment (MCI) may be at particular risk of this. Very little research has examined driving in this population. Given this, we sought to identify predictors of driving cessation in people with MCI. METHODS: One hundred and eighty-five people with MCI were recruited from 9 memory clinics around Australia. People with MCI and their carers reported their driving status and completed measures of cognition, function, neuropsychiatric symptoms, and medication use at regular intervals over a 3-year period. RESULTS: Of the 144 people still driving at baseline, 50 (27.0%) stopped driving during the study. Older age, greater cognitive and functional impairment, and greater decline in cognition and function at 6 months predicted subsequent driving cessation. Twenty-nine of the 50 people (58%) who stopped driving were diagnosed with dementia during the study; all except one of whom ceased driving after their dementia diagnosis. CONCLUSION: A significant proportion of people diagnosed with MCI stop driving over the following 3 years. This cannot be entirely attributed to developing dementia. Easily assessable characteristics - such as age, cognition, and function - and changes in these measures over 6 months predict driving cessation.

Screening for Dementia in Primary Care: A Comparison of the GPCOG and the MMSE.

BACKGROUND/AIMS: The General Practitioner Assessment of Cognition (GPCOG) is a brief cognitive test. This study compared the GPCOG to the Mini-Mental State Examination (MMSE), the most widely used test, in terms of their ability to detect likely dementia in primary care. METHODS: General practitioners across three states in Australia recruited 2,028 elderly patients from the community. A research nurse administered the GPCOG and the MMSE, as well as the Cambridge Examination for Mental Disorders of the Elderly Cognitive Scale-Revised that we used to define likely dementia. RESULTS: Overall, the GPCOG and the MMSE were similarly effective at detecting likely dementia. The GPCOG, however, had a higher sensitivity than the MMSE when using published cutpoints. CONCLUSION: The GPCOG is an effective screening tool for dementia in primary care. It appears to be a viable alternative to the MMSE, whilst also requiring less time to administer.

Beliefs about hearing voices.

People who experience auditory verbal hallucinations (AVHs) vary in whether they believe their AVHs are self-generated or caused by external agents. It remains unclear whether these differences are influenced by the "intensity" of the voices, such as their frequency or volume, or other aspects of their phenomenology. We examined 35 patients with schizophrenia or schizoaffective disorder who experienced AVHs. Patients completed a detailed structured interview about their AVHs, including beliefs about their cause. In response, 20 (57.1%) reported that their AVHs were self-generated, 9 (25.7%) were uncertain, and 6 (17.1%) reported that their AVHs were caused by external agents. Several analytical approaches revealed little or no evidence for associations between either AVH intensity or phenomenology and beliefs about the AVH's cause; the evidence instead favoured the absence of these associations. Beliefs about the cause of AVHs are thus unlikely to be explained solely by the phenomenological qualities of the AVHs.

Hypnosis and belief: A review of hypnotic delusions.

Hypnosis can create temporary, but highly compelling alterations in belief. As such, it can be used to model many aspects of clinical delusions in the laboratory. This approach allows researchers to recreate features of delusions on demand and examine underlying processes with a high level of experimental control. This paper reviews studies that have used hypnosis to model delusions in this way. First, the paper reviews studies that have focused on reproducing the surface features of delusions, such as their high levels of subjective conviction and strong resistance to counter-evidence. Second, the paper reviews studies that have focused on modelling underlying processes of delusions, including anomalous experiences or cognitive deficits that underpin specific delusional beliefs. Finally, the paper evaluates this body of research as a whole. The paper discusses advantages and limitations of using hypnotic models to study delusions and suggests some directions for future research.