Risk factors for hallucinations in Parkinson's disease: results from a large prospective cohort study.

The aim of this study was to identify risk factors for the development of hallucinations in patients with Parkinson's disease (PD). A broad range of motor and nonmotor features was assessed at baseline and during the following 5 years in 386 PD patients. Cross-sectional analyses of baseline data and longitudinal analyses of follow-up data were performed to identify risk factors for hallucinations in PD. Twenty-one percent of the patients had hallucinations at baseline, whereas 46% of the patients without hallucinations at baseline developed this feature during follow-up. Univariate survival analysis showed that older age, female sex, less education, higher age at onset, and more severe motor and cognitive impairment, depression, daytimes sleepiness, autonomic dysfunction, and motor fluctuations and dyskinesias, as well as higher daily levodopa dose, were associated with the risk of developing hallucinations. This largely corresponds with the features that were associated with the presence of hallucinations at baseline. In a stepwise regression model, older age at onset, female sex, excessive daytime sleepiness, autonomic dysfunction, and dyskinesias emerged as independent risk factors for developing hallucinations. Female sex, autonomic dysfunction, motor fluctuations, and dyskinesias have not been reported as risk factors in previous studies. These findings lend support to the notion that hallucinations in PD are caused by a combination of risk factors that are associated with (the interaction between) older age and more advanced disease. The identification of female sex as a risk factor for developing of hallucinations in PD is a new finding and should be verified in future studies.

Clinical phenomenology and mortality in Charles Bonnet syndrome.

BACKGROUND/AIM: Despite existing diagnostic criteria for Charles Bonnet syndrome (CBS), clinical manifestations vary greatly. We examined the clinical course and mortality of patients diagnosed with CBS. METHODS: We conducted a retrospective chart review of patients with CBS. We collected demographic and clinical information and medical burden scores. Kaplan-Meier mortality curves were compared using log-rank test. Cox proportional hazard model was used for multivariate analysis and hazard ratio (HR). Mortality was compared to expected mortality from Minnesota population. RESULTS: Seventy-seven patients with CBS had a mean age of 79.5 (standard deviation ± 13.0) and were predominantly Caucasian (97%) and female (73%). In all, 20 (26%) subsequently developed a dementia syndrome, most often Lewy body. A total of 46 (60%) deaths occurred with an average follow-up time of 33.0 months. Characteristics associated with mortality included older age (75-84 [HR 3.34, P = .029], >85 [HR 4.58, P = .007]) and renal disease (HR 3.39 with 95% confidence interval 1.31-8.80, P = .012). Medical burden scores were not associated with overall mortality. Mortality was high compared to Minnesota population (P < .0001). CONCLUSIONS: A large proportion of patients with CBS developed dementia, and there was a high mortality rate associated with older age and renal disease. Medical burden was not associated with mortality.

Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson's disease patients.

OBJECTIVE: The 10 year outcomes and impact of motor and non-motor features on survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were prospectively studied. METHOD: A cohort of new onset PD patients from 1995 to 2002 was recruited from a regional hospital based movement disorder clinic. Subjects were classified into postural instability gait disorder (PIGD), tremor predominant type or mixed subtypes at presentation. All were evaluated yearly for development of sensory complaints, first significant fall, hallucinations, dementia, postural hypotension, speech disturbances, dysphagia and postural instability persisted during 'on' medication state (PIPon). Mortality and predictors of death were determined. RESULTS: 171 new onset PD patients were recruited. After a mean follow-up of 11.3±2.6 years, 50 (29%) patients died. The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%) developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints. Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101 (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117 (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%) lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI 1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death. CONCLUSIONS: 10 years into PD, a significant proportion of patients developed dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

Associations between symptoms and all-cause mortality in individuals with serious mental illness.

OBJECTIVE: To determine if aggression, hallucinations or delusions, and depression contribute to excess mortality risk observed in individuals with serious mental illness (SMI). METHODS: We identified SMI cases (schizophrenia, schizoaffective and bipolar disorder) aged≥15years in a large secondary mental healthcare case register linked to national mortality tracing. We modelled the effect of specific symptoms (HoNOS subscales) on all-cause mortality using Cox regression. RESULTS: We identified 6880 SMI cases (242 deaths) occurring 2007-2010. Bipolar disorder was associated with reduced mortality risk compared to schizophrenia (HR 0.7; 95% CI 0.4-0.96; p=0.028). Mortality was not significantly associated with hallucinations and delusions or overactive-aggressive behaviour, but was associated with physical illness/disability. There was a positive association between mortality and subclinical depression among individuals with schizophrenia (HR 1.5; 1.1-2.2; p=0.019) but a negative association with subclinical and more severe depression among those with schizoaffective disorder (HR 0.1; 0.02-0.4; p=0.001 and 0.3; 0.1-0.8; p=0.021, respectively). CONCLUSIONS: The recognised increased risk of mortality in SMI did not appear to be influenced by severity of hallucinations, delusions, or overactive-aggressive behaviour. Physical illness and lifestyle may need to be addressed and the relationship between depression and mortality requires further investigation.

The incidence of first-onset psychotic symptoms and paranoid ideation in a representative population sample followed from age 70-90 years. Relation to mortality and later development of dementia.

BACKGROUND: Limited data are available on the incidence of psychotic symptoms in the elderly. OBJECTIVE: To elucidate the incidence of first-onset psychotic symptoms in the elderly and their relation to mortality and later development of dementia. METHOD: A population-sample (n = 392) born 1901-1902 was assessed from age 70-90 with psychiatric examinations, medical record reviews and from age 85, also with key-informant interviews. Individuals developing dementia were excluded. RESULT: The cumulative incidence of first-onset psychotic symptoms was 4.8% (8.0% including key-informant reports in the total sample) and 19.8 % in those who survived to age 85. Sixty-four percent of those with first-onset hallucinations later developed dementia, compared to 30% of those with delusions and 25% of those without psychotic symptoms. CONCLUSIONS: One fifth of non-demented elderly who survives up to age 85 develops first-onset psychotic symptoms. Hallucinations predict dementia, but most elderly individuals with first-onset psychotic symptoms do not develop dementia.

Hallucinations and mortality in Alzheimer disease.

OBJECTIVE: The authors tested the relationship of hallucinations and delusions to mortality in Alzheimer disease (AD). METHODS: A group of 407 persons with clinically diagnosed AD completed a uniform clinical evaluation, after which vital status was monitored for a mean of 3.7 years. At the initial evaluation, a previously established, structured, informant interview was used to ascertain the presence of hallucinations and delusional thinking. The evaluation also included a structured medical history, inspection of all medications, and detailed assessment of cognitive functioning and parkinsonian signs. RESULTS: At study onset, hallucinations were present in 41.0% of participants and delusions in 54.4%. During follow-up, 146 deaths occurred. In a proportional-hazards model adjusted for age, sex, race, and education, hallucinations were associated with a 78% increase in risk of death. The association was not substantially altered in subsequent analyses that controlled for level of cognitive impairment, severity of parkinsonism, use of antipsychotic medications, and the presence of chronic medical conditions. Risk of death was more than doubled in those with both auditory and visual hallucinations. By contrast, we did not find evidence of an association of delusions with mortality. CONCLUSION: Hallucinations are associated with an increased risk of death in AD.