User login
REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), and a high burden of autonomic symptoms are associated with increased risk of future psychotic symptoms in patients with Parkinson’s disease, according to research published online ahead of print April 4 in Neurology. These symptoms also correlate with low density of the cholinergic nucleus 4 (Ch4) of the basal forebrain.
Data From the Parkinson’s Progression Markers Initiative
Parkinson’s disease psychosis indicates advanced disease and is associated with dementia and increased mortality. Research indicates that degeneration of the nucleus basalis of Meynert is characteristic of Parkinson’s disease and Parkinson’s disease dementia, but this brain region is difficult to measure with MRI because of its size. It is possible, however, to measure Ch4, which incorporates the nucleus basalis of Meynert.
Matthew J. Barrett, MD, Assistant Professor of Neurology at the University of Virginia in Charlottesville, and colleagues studied a cohort of patients with de novo Parkinson’s disease to identify baseline clinical risk factors for future psychotic symptoms and to assess the relationship between baseline Ch4 density and future psychotic symptoms. All participants were untreated at baseline and had enrolled in the Parkinson’s Progression Markers Initiative (PPMI), a prospective, longitudinal, observational study. 
Physicians assessed participants with the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) at each visit. Item 1.2 assesses hallucinations and psychosis during the previous week. The investigators considered any score above 0 on this item to indicate the presence of psychotic symptoms.
Investigators evaluated patients’ autonomic symptoms with the Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT) and administered the RBD screening questionnaire and the Epworth Sleepiness Scale. They determined the density of each participant’s basal forebrain using brain MRI sequences that they obtained from the PPMI database.
Ch4 Density Could Predict Psychotic Symptoms
The investigators included 423 participants in their analysis. The population’s mean age at enrollment was approximately 61.5, and about 35% of the population was female. Mean disease duration was 0.57 years. The population’s median number of clinical visits was 11, and the median last visit occurred at 54 months after baseline.
In all, 138 participants (32.6%) reported psychotic symptoms at least once, and 84 (19.9%) reported them more than once. Dr. Barrett and colleagues identified 17 patients who, having once reported psychotic symptoms, reported these symptoms at each subsequent visit. Among patients who reported psychotic symptoms, approximately 79% reported them at only one visit.
The investigators categorized patients into three groups according to the number of psychotic events. The groups included participants with no psychotic events, those with one psychotic event, and those with two or more psychotic events.
After performing multivariate logistic regression and adjusting the results for age and sex, Dr. Barrett and colleagues found that greater autonomic symptoms (odds ratio [OR], 1.07 for a one-unit change in SCOPA-AUT), the presence of RBD (OR, 1.9), and EDS (OR, 2.5) at baseline were associated with increased risk of reporting psychotic symptoms on two or more occasions, compared to no or one psychotic event.
A logistic regression model adjusted for age and sex indicated that greater autonomic symptoms (OR, 1.08 for a one-unit change in SCOPA-AUT) and EDS (OR, 1.8) at baseline were associated with increased risk of psychotic symptoms on one or more occasions. A Cox regression model adjusted for EDS (hazard ratio [HR], 1.5) indicated that greater autonomic symptoms (HR, 1.03 for a one-unit change in SCOPA-AUT) and presence of RBD (HR, 1.47) were associated with increased risk of having a first psychotic event.
At the last assessment, patients with Parkinson’s disease and two or more psychotic events were more likely to have the postural instability and gait difficulty motor phenotype and lower scores on the Montreal Cognitive Assessment, Letter Number Sequencing test, and Symbol Digit Modalities Test.
The investigators had data about cholinergic nuclei densities at baseline for 228 participants with Parkinson’s disease and 101 controls. Ch4 density in Parkinson’s disease was associated with lower risk of reporting psychotic symptoms on two or more occasions (OR, 0.96 for an increase in density of one unit). Mean Ch4 densities were 1.7% greater for the control group, compared with the Parkinson’s disease group. Participants with Parkinson’s disease and two or more psychotic events had lower baseline Ch4 density, compared with healthy controls, but participants with Parkinson’s disease with no or one psychotic event did not.
In linear regression models adjusted for age and sex, autonomic symptoms were associated with baseline Ch4 density, but EDS and RBD were not. Having comorbid EDS and RBD was associated with lower Ch4 density.
Results Do Not Establish Causation
“Prior studies reported that EDS was associated with hallucinations in Parkinson’s disease, but we are not aware of other studies that found EDS to be a predictor of future psychotic symptoms,” said Dr. Barrett and colleagues.
“In univariate comparisons, participants with Parkinson’s disease with three or more psychotic events had worse visuospatial function, compared with those with two psychotic events. Considering the greater impairment in visuospatial and visuoperceptive function reported in Parkinson’s disease with visual hallucinations, this association should be evaluated in the future in the PPMI Parkinson’s disease cohort as additional follow-up visits occur.”
The current study’s finding of an association between autonomic dysfunction, RBD, and EDS and baseline Ch4 density in Parkinson’s disease is consistent with a recent analysis that found that the same symptoms were associated with a diffuse malignant subtype of Parkinson’s disease, said the authors. “Our finding that these three nonmotor symptoms are linked to future psychotic symptoms validates the prognostic value of these symptoms in predicting worse outcomes early in disease.”
Evidence does not support a causal relationship between lower Ch4 density and autonomic dysfunction, RBD, and EDS. These four characteristics may be associated with widespread subcortical pathology. “The relationship between this triad of clinical symptoms and lower Ch4 density supports the potential utility of this neuroimaging biomarker to identify a diffuse malignant subtype of Parkinson’s disease and to predict more rapid disease progression,” said Dr. Barrett and colleagues.
—Erik Greb
Suggested Reading
Barrett MJ, Blair JC, Sperling SA, et al. Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease. Neurology. 2018 Apr 4 [Epub ahead of print].
Bohnen NI, Teipel SJ. Cholinergic forebrain density loss in Parkinson disease: More than just cognitive changes. Neurology. 2018 Apr 4 [Epub ahead of print].
REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), and a high burden of autonomic symptoms are associated with increased risk of future psychotic symptoms in patients with Parkinson’s disease, according to research published online ahead of print April 4 in Neurology. These symptoms also correlate with low density of the cholinergic nucleus 4 (Ch4) of the basal forebrain.
Data From the Parkinson’s Progression Markers Initiative
Parkinson’s disease psychosis indicates advanced disease and is associated with dementia and increased mortality. Research indicates that degeneration of the nucleus basalis of Meynert is characteristic of Parkinson’s disease and Parkinson’s disease dementia, but this brain region is difficult to measure with MRI because of its size. It is possible, however, to measure Ch4, which incorporates the nucleus basalis of Meynert.
Matthew J. Barrett, MD, Assistant Professor of Neurology at the University of Virginia in Charlottesville, and colleagues studied a cohort of patients with de novo Parkinson’s disease to identify baseline clinical risk factors for future psychotic symptoms and to assess the relationship between baseline Ch4 density and future psychotic symptoms. All participants were untreated at baseline and had enrolled in the Parkinson’s Progression Markers Initiative (PPMI), a prospective, longitudinal, observational study.
Physicians assessed participants with the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) at each visit. Item 1.2 assesses hallucinations and psychosis during the previous week. The investigators considered any score above 0 on this item to indicate the presence of psychotic symptoms.
Investigators evaluated patients’ autonomic symptoms with the Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT) and administered the RBD screening questionnaire and the Epworth Sleepiness Scale. They determined the density of each participant’s basal forebrain using brain MRI sequences that they obtained from the PPMI database.
Ch4 Density Could Predict Psychotic Symptoms
The investigators included 423 participants in their analysis. The population’s mean age at enrollment was approximately 61.5, and about 35% of the population was female. Mean disease duration was 0.57 years. The population’s median number of clinical visits was 11, and the median last visit occurred at 54 months after baseline.
In all, 138 participants (32.6%) reported psychotic symptoms at least once, and 84 (19.9%) reported them more than once. Dr. Barrett and colleagues identified 17 patients who, having once reported psychotic symptoms, reported these symptoms at each subsequent visit. Among patients who reported psychotic symptoms, approximately 79% reported them at only one visit.
The investigators categorized patients into three groups according to the number of psychotic events. The groups included participants with no psychotic events, those with one psychotic event, and those with two or more psychotic events.
After performing multivariate logistic regression and adjusting the results for age and sex, Dr. Barrett and colleagues found that greater autonomic symptoms (odds ratio [OR], 1.07 for a one-unit change in SCOPA-AUT), the presence of RBD (OR, 1.9), and EDS (OR, 2.5) at baseline were associated with increased risk of reporting psychotic symptoms on two or more occasions, compared to no or one psychotic event.
A logistic regression model adjusted for age and sex indicated that greater autonomic symptoms (OR, 1.08 for a one-unit change in SCOPA-AUT) and EDS (OR, 1.8) at baseline were associated with increased risk of psychotic symptoms on one or more occasions. A Cox regression model adjusted for EDS (hazard ratio [HR], 1.5) indicated that greater autonomic symptoms (HR, 1.03 for a one-unit change in SCOPA-AUT) and presence of RBD (HR, 1.47) were associated with increased risk of having a first psychotic event.
At the last assessment, patients with Parkinson’s disease and two or more psychotic events were more likely to have the postural instability and gait difficulty motor phenotype and lower scores on the Montreal Cognitive Assessment, Letter Number Sequencing test, and Symbol Digit Modalities Test.
The investigators had data about cholinergic nuclei densities at baseline for 228 participants with Parkinson’s disease and 101 controls. Ch4 density in Parkinson’s disease was associated with lower risk of reporting psychotic symptoms on two or more occasions (OR, 0.96 for an increase in density of one unit). Mean Ch4 densities were 1.7% greater for the control group, compared with the Parkinson’s disease group. Participants with Parkinson’s disease and two or more psychotic events had lower baseline Ch4 density, compared with healthy controls, but participants with Parkinson’s disease with no or one psychotic event did not.
In linear regression models adjusted for age and sex, autonomic symptoms were associated with baseline Ch4 density, but EDS and RBD were not. Having comorbid EDS and RBD was associated with lower Ch4 density.
Results Do Not Establish Causation
“Prior studies reported that EDS was associated with hallucinations in Parkinson’s disease, but we are not aware of other studies that found EDS to be a predictor of future psychotic symptoms,” said Dr. Barrett and colleagues.
“In univariate comparisons, participants with Parkinson’s disease with three or more psychotic events had worse visuospatial function, compared with those with two psychotic events. Considering the greater impairment in visuospatial and visuoperceptive function reported in Parkinson’s disease with visual hallucinations, this association should be evaluated in the future in the PPMI Parkinson’s disease cohort as additional follow-up visits occur.”
The current study’s finding of an association between autonomic dysfunction, RBD, and EDS and baseline Ch4 density in Parkinson’s disease is consistent with a recent analysis that found that the same symptoms were associated with a diffuse malignant subtype of Parkinson’s disease, said the authors. “Our finding that these three nonmotor symptoms are linked to future psychotic symptoms validates the prognostic value of these symptoms in predicting worse outcomes early in disease.”
Evidence does not support a causal relationship between lower Ch4 density and autonomic dysfunction, RBD, and EDS. These four characteristics may be associated with widespread subcortical pathology. “The relationship between this triad of clinical symptoms and lower Ch4 density supports the potential utility of this neuroimaging biomarker to identify a diffuse malignant subtype of Parkinson’s disease and to predict more rapid disease progression,” said Dr. Barrett and colleagues.
—Erik Greb
Suggested Reading
Barrett MJ, Blair JC, Sperling SA, et al. Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease. Neurology. 2018 Apr 4 [Epub ahead of print].
Bohnen NI, Teipel SJ. Cholinergic forebrain density loss in Parkinson disease: More than just cognitive changes. Neurology. 2018 Apr 4 [Epub ahead of print].
REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), and a high burden of autonomic symptoms are associated with increased risk of future psychotic symptoms in patients with Parkinson’s disease, according to research published online ahead of print April 4 in Neurology. These symptoms also correlate with low density of the cholinergic nucleus 4 (Ch4) of the basal forebrain.
Data From the Parkinson’s Progression Markers Initiative
Parkinson’s disease psychosis indicates advanced disease and is associated with dementia and increased mortality. Research indicates that degeneration of the nucleus basalis of Meynert is characteristic of Parkinson’s disease and Parkinson’s disease dementia, but this brain region is difficult to measure with MRI because of its size. It is possible, however, to measure Ch4, which incorporates the nucleus basalis of Meynert.
Matthew J. Barrett, MD, Assistant Professor of Neurology at the University of Virginia in Charlottesville, and colleagues studied a cohort of patients with de novo Parkinson’s disease to identify baseline clinical risk factors for future psychotic symptoms and to assess the relationship between baseline Ch4 density and future psychotic symptoms. All participants were untreated at baseline and had enrolled in the Parkinson’s Progression Markers Initiative (PPMI), a prospective, longitudinal, observational study.
Physicians assessed participants with the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) at each visit. Item 1.2 assesses hallucinations and psychosis during the previous week. The investigators considered any score above 0 on this item to indicate the presence of psychotic symptoms.
Investigators evaluated patients’ autonomic symptoms with the Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT) and administered the RBD screening questionnaire and the Epworth Sleepiness Scale. They determined the density of each participant’s basal forebrain using brain MRI sequences that they obtained from the PPMI database.
Ch4 Density Could Predict Psychotic Symptoms
The investigators included 423 participants in their analysis. The population’s mean age at enrollment was approximately 61.5, and about 35% of the population was female. Mean disease duration was 0.57 years. The population’s median number of clinical visits was 11, and the median last visit occurred at 54 months after baseline.
In all, 138 participants (32.6%) reported psychotic symptoms at least once, and 84 (19.9%) reported them more than once. Dr. Barrett and colleagues identified 17 patients who, having once reported psychotic symptoms, reported these symptoms at each subsequent visit. Among patients who reported psychotic symptoms, approximately 79% reported them at only one visit.
The investigators categorized patients into three groups according to the number of psychotic events. The groups included participants with no psychotic events, those with one psychotic event, and those with two or more psychotic events.
After performing multivariate logistic regression and adjusting the results for age and sex, Dr. Barrett and colleagues found that greater autonomic symptoms (odds ratio [OR], 1.07 for a one-unit change in SCOPA-AUT), the presence of RBD (OR, 1.9), and EDS (OR, 2.5) at baseline were associated with increased risk of reporting psychotic symptoms on two or more occasions, compared to no or one psychotic event.
A logistic regression model adjusted for age and sex indicated that greater autonomic symptoms (OR, 1.08 for a one-unit change in SCOPA-AUT) and EDS (OR, 1.8) at baseline were associated with increased risk of psychotic symptoms on one or more occasions. A Cox regression model adjusted for EDS (hazard ratio [HR], 1.5) indicated that greater autonomic symptoms (HR, 1.03 for a one-unit change in SCOPA-AUT) and presence of RBD (HR, 1.47) were associated with increased risk of having a first psychotic event.
At the last assessment, patients with Parkinson’s disease and two or more psychotic events were more likely to have the postural instability and gait difficulty motor phenotype and lower scores on the Montreal Cognitive Assessment, Letter Number Sequencing test, and Symbol Digit Modalities Test.
The investigators had data about cholinergic nuclei densities at baseline for 228 participants with Parkinson’s disease and 101 controls. Ch4 density in Parkinson’s disease was associated with lower risk of reporting psychotic symptoms on two or more occasions (OR, 0.96 for an increase in density of one unit). Mean Ch4 densities were 1.7% greater for the control group, compared with the Parkinson’s disease group. Participants with Parkinson’s disease and two or more psychotic events had lower baseline Ch4 density, compared with healthy controls, but participants with Parkinson’s disease with no or one psychotic event did not.
In linear regression models adjusted for age and sex, autonomic symptoms were associated with baseline Ch4 density, but EDS and RBD were not. Having comorbid EDS and RBD was associated with lower Ch4 density.
Results Do Not Establish Causation
“Prior studies reported that EDS was associated with hallucinations in Parkinson’s disease, but we are not aware of other studies that found EDS to be a predictor of future psychotic symptoms,” said Dr. Barrett and colleagues.
“In univariate comparisons, participants with Parkinson’s disease with three or more psychotic events had worse visuospatial function, compared with those with two psychotic events. Considering the greater impairment in visuospatial and visuoperceptive function reported in Parkinson’s disease with visual hallucinations, this association should be evaluated in the future in the PPMI Parkinson’s disease cohort as additional follow-up visits occur.”
The current study’s finding of an association between autonomic dysfunction, RBD, and EDS and baseline Ch4 density in Parkinson’s disease is consistent with a recent analysis that found that the same symptoms were associated with a diffuse malignant subtype of Parkinson’s disease, said the authors. “Our finding that these three nonmotor symptoms are linked to future psychotic symptoms validates the prognostic value of these symptoms in predicting worse outcomes early in disease.”
Evidence does not support a causal relationship between lower Ch4 density and autonomic dysfunction, RBD, and EDS. These four characteristics may be associated with widespread subcortical pathology. “The relationship between this triad of clinical symptoms and lower Ch4 density supports the potential utility of this neuroimaging biomarker to identify a diffuse malignant subtype of Parkinson’s disease and to predict more rapid disease progression,” said Dr. Barrett and colleagues.
—Erik Greb
Suggested Reading
Barrett MJ, Blair JC, Sperling SA, et al. Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease. Neurology. 2018 Apr 4 [Epub ahead of print].
Bohnen NI, Teipel SJ. Cholinergic forebrain density loss in Parkinson disease: More than just cognitive changes. Neurology. 2018 Apr 4 [Epub ahead of print].