Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease

ObjectiveDetermining baseline predictors of future psychosis in Parkinson disease (PD) may identify those at risk for more rapidly progressive disease, i.e., a more malignant PD subtype.MethodsThis cohort study evaluated 423 patients with newly diagnosed PD collected as part of the Parkinson's Progression Markers Initiative. Psychotic symptoms were assessed with the Movement Disorders Society–Unified Parkinson Disease Rating Scale item 1.2, which assesses hallucinations and psychosis over the past week. At baseline, participants completed the Scales for Outcomes in Parkinson's Disease–Autonomic, the REM Sleep Behavior Disorder (RBD) Screening Questionnaire, and the Epworth Sleepiness Scale. Cholinergic nucleus 4 (Ch4) density was calculated for 228 participants with PD and 101 healthy controls.ResultsMultivariate logistic regression adjusted for age and sex found that greater autonomic symptoms (p = 0.002), RBD (p = 0.021), and excessive daytime sleepiness (EDS) (p = 0.003) at baseline were associated with increased risk of reporting psychotic symptoms on ≥2 occasions. Having 2 or 3 of these baseline symptoms was associated with lower Ch4 density (p = 0.007). In a logistic regression model adjusted for age and sex, higher Ch4 gray matter density was associated with lower risk of reporting psychotic symptoms on ≥2 occasions (odds ratio 0.96 [for an increase in density of 1 unit], p = 0.03).ConclusionsThis study confirms that RBD, EDS, and greater autonomic symptom burden are associated with greater risk of future psychotic symptoms in PD. Reduced Ch4 density at baseline is associated with future psychotic symptoms and a greater burden of RBD, EDS, and autonomic symptoms.

Download Full-text

Association of specific biotypes in patients with Parkinson disease and disease progression

Neurology ◽

10.1212/wnl.0000000000010498 ◽

2020 ◽

Vol 95 (11) ◽

pp. e1445-e1460 ◽

Cited By ~ 1

Author(s):

Linbo Wang ◽

Wei Cheng ◽

Edmund T. Rolls ◽

Fuli Dai ◽

Weikang Gong ◽

...

Keyword(s):

Parkinson Disease ◽

Rating Scale ◽

Functional Neuroimaging ◽

Rem Sleep Behavior Disorder ◽

Hierarchical Cluster ◽

Rapid Decline ◽

Sleep Behavior ◽

Brain Volumes ◽

Subcortical Brain

ObjectiveTo identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression.MethodsIn this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale Parts I–III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes.ResultsTwo neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years.ConclusionRobust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.

Download Full-text

Probable REM Sleep Behavior Disorder Is a Risk Factor for Symptom Progression in Parkinson Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.651157 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ashley Barasa ◽

Jijia Wang ◽

Richard B. Dewey

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Parkinson Disease ◽

Rating Scale ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Rate Of Change ◽

Rapid Progression ◽

Sleep Behavior ◽

Updrs Part

Background: The literature is conflicting on whether rapid eye movement sleep behavior disorder (RBD) is associated with more rapid progression of Parkinson disease (PD).Objective: We aimed to determine (1) how stable probable RBD (pRBD) is over time and (2) whether it predicts faster PD progression.Methods: We evaluated participants in the Parkinson's Disease Biomarker Project (PDBP) who were prospectively assessed every 6–12 months with a series of motor, non-motor, disability, and health status scales. For aim 1, we calculated the incidence and disappearance rates of pRBD and compared stability of pRBD in PD with control subjects. For aim 2, we developed multiple regression models to determine if pRBD at baseline influenced the rate of change or average value at 48 months of 10 outcome variables.Results: We found that pRBD was a less stable diagnosis for PD than controls. In pRBD+ subjects, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score progressed 2.78 points per year faster (p < 0.01), MDS-UPDRS total score progressed 3.98 points per year faster (p < 0.01), a global composite outcome (GCO) worsened by 0.09 points per year faster (p = 0.02), and Parkinson's Disease Questionnaire (PDQ-39) mobility score progressed 2.57 percentage points per year faster (p < 0.01). The average scores at 48 months were 8.89 (p = 0.02) and 14.3 (p = 0.01) points higher for pRBD+ in MDS-UPDRS part III and total scores, respectively.Conclusions: Our study confirms that pRBD detected at the start of a study portends more rapid progression of PD. Knowing this could be useful for enriching clinical trials with fast progressors to accelerate discovery of a disease modifying agent.

Download Full-text

The use of an antagonist 5-HT2a/c for depression and motor function in Parkinson' disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000300007 ◽

2009 ◽

Vol 67 (2b) ◽

pp. 407-412 ◽

Cited By ~ 25

Author(s):

Antonio Luiz dos Santos Werneck ◽

Ana Lucia Rosso ◽

Maurice Borges Vincent

Keyword(s):

Parkinson Disease ◽

Motor Function ◽

Rating Scale ◽

Statistical Significance ◽

Psychotic Symptoms ◽

Initial Moment ◽

The Mean ◽

Group 2 ◽

To Receive ◽

Group 1

OBJECTIVE: To test the ability of a 5HT2a/c (trazodone) antagonist, to improve depression and motor function in Parkinson' disease (PD). METHOD: Twenty PD patients with and without depression were randomly assigned to receive trazodone (group 1) or not (group 2). They were evaluated through UPDRS and Hamilton Depression Rating Scale (HAM-D). RESULTS: For the UPDRS the mean score of group 2 was 33.1 ± 19.7 and 37.1 ± 18.0 at the end. For the group 1, the corresponding scores were 31.4 ± 11.3 and 25.9 ± 13.7. The variations in the Mann-Whitney test were 0.734 at the initial moment and 0.208 at the final moment. The variation in the comparison of the initial moment with the final moment was 0.005 providing statistical significance. For the HAM-D, the mean score went up 4 points in group 2, contrary to a 5.5 points decrease in group 1. CONCLUSION: Data analysis shows that this agent significantly improves depression, but the motor function improved only in the depressed patients. Because of the known anti-dopaminergic property of the 5-HT2c receptors, a possible approach for depression in PD could be the use of 5-HT2c antagonists, similarly to the use of atypical neuroleptics in case of psychotic symptoms.

Download Full-text

A predictive model to identify Parkinson disease from administrative claims data

Neurology ◽

10.1212/wnl.0000000000004536 ◽

2017 ◽

Vol 89 (14) ◽

pp. 1448-1456 ◽

Cited By ~ 18

Author(s):

Susan Searles Nielsen ◽

Mark N. Warden ◽

Alejandra Camacho-Soto ◽

Allison W. Willis ◽

Brenton A. Wright ◽

...

Keyword(s):

Parkinson Disease ◽

Predictive Model ◽

Claims Data ◽

Demographic Data ◽

Area Under The Curve ◽

Rem Sleep Behavior Disorder ◽

Administrative Claims ◽

Sleep Behavior ◽

Administrative Claims Data ◽

Procedure Codes

Objective:To use administrative medical claims data to identify patients with incident Parkinson disease (PD) prior to diagnosis.Methods:Using a population-based case-control study of incident PD in 2009 among Medicare beneficiaries aged 66–90 years (89,790 cases, 118,095 controls) and the elastic net algorithm, we developed a cross-validated model for predicting PD using only demographic data and 2004–2009 Medicare claims data. We then compared this model to more basic models containing only demographic data and diagnosis codes for constipation, taste/smell disturbance, and REM sleep behavior disorder, using each model's receiver operator characteristic area under the curve (AUC).Results:We observed all established associations between PD and age, sex, race/ethnicity, tobacco smoking, and the above medical conditions. A model with those predictors had an AUC of only 0.670 (95% confidence interval [CI] 0.668–0.673). In contrast, the AUC for a predictive model with 536 diagnosis and procedure codes was 0.857 (95% CI 0.855–0.859). At the optimal cut point, sensitivity was 73.5% and specificity was 83.2%.Conclusions:Using only demographic data and selected diagnosis and procedure codes readily available in administrative claims data, it is possible to identify individuals with a high probability of eventually being diagnosed with PD.

Download Full-text

Predictors of Pharyngeal Dysphagia in Patients with Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202081 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1727-1735

Author(s):

Inga Claus ◽

Paul Muhle ◽

Judith Suttrup ◽

Bendix Labeit ◽

Sonja Suntrup-Krueger ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Logistic Regression ◽

Rating Scale ◽

Equivalent Dose ◽

Binary Logistic Regression Analysis ◽

Screening Methods ◽

Clinical Predictors ◽

Pharyngeal Dysphagia ◽

Increased Risk

Background: Diagnosis of pharyngeal dysphagia in patients with Parkinson’s disease is often difficult as reliable screening methods are lacking so far and clinical examination fails to adequately assess the pharyngeal phase of swallowing. Objective: To identify clinical predictors indicating the presence of pharyngeal dysphagia in patients at risk. Methods: We examined pharyngeal dysphagia in a large cohort of patients with Parkinson’s disease (n = 200) divided in three clinical subtypes (tremor-dominant (TD), mainly bradykinetic (BK) and early postural instability and gait difficulty PIGD)) by using flexible endoscopic evaluation of swallowing. ANOVA-multivariance analysis and following t-tests as well as binary logistic regression analysis were performed to detect group differences and to identify clinical predictors for dysphagia. Results: Statistically significant differences were found in the dysphagic group: age, male gender, disease duration, stage of the disease, Levodopa equivalent dose and higher scores on the Unified Parkinson’s disease rating scale III and II, item 7. The PIGD subtype was affected more frequently than the TD and BK subtype. In a logistic regression model higher age (>63.5 years p < 0.05) and Levodopa equivalent dose (>475 mg, p < 0.01) were identified to be independent predictors for the presence of pharyngeal dysphagia. Conclusion: Particularly patients with an age > 63.5 years and a daily Levodopa equivalent dose >475 mg show an increased risk for pharyngeal dysphagia. These findings may partly be influenced by presbyphagia but are likely to represent disease progression. The PIGD subtype seems to be a risk factor due to more pronounced dyscoordination of oropharyngeal muscle movements.

Download Full-text

Physical activity and prodromal features of Parkinson disease

Neurology ◽

10.1212/wnl.0000000000008567 ◽

2019 ◽

Vol 93 (23) ◽

pp. e2157-e2169 ◽

Cited By ~ 6

Author(s):

Katherine C. Hughes ◽

Xiang Gao ◽

Samantha Molsberry ◽

Linda Valeri ◽

Michael A. Schwarzschild ◽

...

Keyword(s):

Physical Activity ◽

Parkinson Disease ◽

Bodily Pain ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Health Study ◽

Older Individuals ◽

Sleep Behavior ◽

Physically Active ◽

Baseline Physical Activity

ObjectiveTo investigate the relationship between physical activity and prodromal features of Parkinson disease that often precede the clinical diagnosis.MethodsIncluded are participants in 2 well-established cohorts: the Nurses' Health Study and the Health Professionals Follow-up Study. Physical activity was assessed using validated questionnaires at baseline (1986) and every 2 years until 2008. Prodromal features (e.g., constipation, hyposmia, and probable REM sleep behavior disorder [pRBD]) were assessed in 2012–2014.ResultsThe multivariable-adjusted odds ratio (OR) for having ≥3 prodromal features vs none comparing the highest to the lowest quintile were 0.65 (95% confidence interval [CI] 0.53–0.79; ptrend = 0.0006) for baseline physical activity and 0.52 (95% CI 0.35–0.76; ptrend = 0.009) for cumulative average physical activity. Considering each feature independently, baseline physical activity was associated with lower odds of constipation (OR 0.78, 95% CI 0.73–0.83; ptrend < 0.0001), excessive daytime sleepiness (OR 0.72, 95% CI 0.60–0.86; ptrend = 0.002), depressive symptoms (OR 0.82, 95% CI 0.69–0.97; ptrend = 0.13), and bodily pain (OR 0.81, 95% CI 0.68–0.96; ptrend = 0.03). Similar or stronger associations were observed for cumulative average physical activity, which, in addition, was associated with pRBD (OR 0.85, 95% CI 0.77–0.95; ptrend = 0.02). In contrast, neither hyposmia nor impaired color vision was associated with physical activity. Early life physical activity was associated with constipation and, in men only, with the co-occurrence of ≥3 features.ConclusionsThe reduced prevalence of prodromal features associated with Parkinson disease in older individuals who were more physically active in midlife and beyond is consistent with the hypothesis that high levels of physical activity may reduce risk of Parkinson disease.

Download Full-text

Minor hallucinations in Parkinson disease

Neurology ◽

10.1212/wnl.0000000000007913 ◽

2019 ◽

Vol 93 (6) ◽

pp. 259-266 ◽

Cited By ~ 18

Author(s):

Abhishek Lenka ◽

Javier Pagonabarraga ◽

Pramod Kumar Pal ◽

Helena Bejr-Kasem ◽

Jaime Kulisvesky

Keyword(s):

Parkinson Disease ◽

Visual Processing ◽

Brain Connectivity ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Future Directions ◽

Sleep Behavior ◽

Control Networks ◽

Pubmed Search ◽

Prognostic Implications

ObjectivePsychosis is one of the most debilitating complications of Parkinson disease (PD). Although research on PD psychosis has been focused on the study of well-structured visual hallucinations (VH), currently accepted National Institute of Neurological Disorders and Stroke–National Institute of Mental Health diagnostic criteria emphasize minor hallucinations (MH) as the most common psychotic phenomena in PD. The objective of this review is to comprehensively describe the clinical and research advances on the understanding of MH and to provide future directions for obtaining further insights into their potential major implications for PD management and prognosis.MethodsA PubMed search was done in November 2018 to identify articles on minor psychotic phenomena in PD.ResultsMH often precede the onset of well-structured VH and are associated with other nonmotor symptoms such as REM sleep behavior disorder and depression. The pattern of functional brain connectivity changes associated with MH involve visual-processing areas and attention control networks, which overlap with abnormalities described in patients with well-structured VH. The dysfunction of cortical networks in patients with MH may be an early indicator of a more widespread form of the disease.ConclusionAlthough called “minor,” MH may have major clinical and prognostic implications. Further research is needed to establish whether MH are associated with a higher risk of disabling psychotic complications, cognitive deterioration, or a more accelerated disease progression. Understanding the early neurobiological underpinnings of MH may provide the background for future studies to identify the progressive dysfunction of neural circuits leading to more severe forms of psychosis in PD.

Download Full-text

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

npj Parkinson s Disease ◽

10.1038/s41531-021-00219-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Luca Baldelli ◽

Sebastian Schade ◽

Silvia Jesús ◽

Sebastian R. Schreglmann ◽

Luisa Sambati ◽

...

Keyword(s):

De Novo ◽

Motor Impairment ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Prodromal Phase ◽

Sleep Behavior ◽

Heterogeneous Distribution ◽

Increased Risk ◽

Non Motor Symptoms ◽

German Part

AbstractA prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated.

Download Full-text