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

Neurology ◽  
2020 ◽  
Vol 95 (11) ◽  
pp. e1445-e1460 ◽  
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.

scholarly journals Evolution of prodromal parkinsonian features in a cohort of GBA mutation-positive individuals: a 6-year longitudinal study

2019 ◽  
Vol 90 (10) ◽  
pp. 1091-1097 ◽  
Author(s):  
Micol Avenali ◽  
Marco Toffoli ◽  
Stephen Mullin ◽  
Alisdair McNeil ◽  
Derralynn A Hughes ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Rating Scale ◽  
Venous Blood ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Activity Level ◽  
University Of Pennsylvania ◽  
Sleep Behavior ◽  
Disease Rating

ObjectivesGBA1 mutations are a frequent risk factor for Parkinson disease (PD). The aim of this study is to evaluate clinical features in a group of GBA1 mutation–positive individuals over a 6-year follow-up.MethodsThis is a longitudinal study on a cohort of GBA1-positive carriers. We enrolled 31 patients with Gaucher disease type 1 (GD), 29 GBA1 heterozygous carriers (Het GBA group) and 30 controls (HC) at baseline and followed them for 6 years. We assessed baseline motor and non-motor signs of PD in all subjects using clinical questionnaires and scales (reduced Unified Multiple System Atrophy Rating Scale (UMSARS), Montreal Cognitive assessment (MoCA), University of Pennsylvania Smell Identification Test (UPSIT), REM Sleep Behavior Disorder screening questionnaire (RBDsq), Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor subscale (MDS-UPDRS III) and Beck Depression Inventory (BDI). We repeated these at the 6-year follow-up alongside venous blood sampling for measurement of glucocerebrosidase enzymatic activity (GCase). We explored whether the GCase activity level was altered in leucocytes of these subjects and how it was related to development of PD.ResultsWe observed a significant worsening in UMSARS, RBDsq, MDS-UPDRS III and BDI scores at the 6-year follow-up compared with baseline in both the GD and Het GBA groups. Intergroup comparisons showed that GD subjects had significantly worse scores in UPSIT, UMSARS, MoCA and MDS-UPDRS III than HC, while Het GBA displayed worse outcomes in UPSIT and MDS-UPDRS III compared with HC. In GBA1 mutation–positive individuals (Het GBA and GD), an UPSIT score of 23 at baseline was correlated with worse outcome at 6 years in UPSIT, MoCA, MDS-UPDRS III and BDI.ConclusionIn this 6-year-long longitudinal study, GBA1 mutation–positive subjects showed a worsening in motor and non-motor prodromal PD features.

Characterization of patients with longstanding idiopathic REM sleep behavior disorder

Neurology ◽  
2017 ◽  
Vol 89 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Alex Iranzo ◽  
Ambra Stefani ◽  
Monica Serradell ◽  
Maria Jose Martí ◽  
Francisco Lomeña ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Rating Scale ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Transcranial Sonography ◽  
Sleep Behavior ◽  
Neurodegenerative Process ◽  
Small Subgroup ◽  
Long Term Follow Up

Objective:To evaluate the presence of prodromal markers of Parkinson disease (PD) in patients with longstanding idiopathic REM sleep behavior disorder (IRBD), a small subgroup of individuals with IRBD with long-term follow-up thought not to be at risk of developing PD.Methods:Demographic, clinical, and neuroimaging markers of PD were evaluated in 20 patients with polysomnographic-confirmed longstanding IRBD and in 32 matched controls.Results:Patients were 16 men and 4 women with mean age of 72.9 ± 8.6 years and mean follow-up from IRBD diagnosis of 12.1 ± 2.6 years. Patients more often had objective smell loss (35% vs 3.4%, p = 0.003), constipation (50% vs 15.6%, p = 0.008), and mild parkinsonian signs (45% vs 18.8%, p = 0.042) than controls. Unified Parkinson's Disease Rating Scale motor score was higher in patients than in controls (5.6 ± 3.5 vs 2.0 ± 2.1, p < 0.0001). Dopamine transporter imaging showed decreased striatal uptake in 82.4% of the patients and transcranial sonography found substantia nigra hyperechogenicity in 35.3%. α-Synuclein aggregates were found in 3 of 6 patients who underwent colon or submandibular gland biopsies. All 20 patients showed clinical, neuroimaging, or histologic markers of PD. Probability of prodromal PD (according to recent Movement Disorders Society research criteria) was higher in patients than in controls (<0.0001), and 45% of patients surpassed 80% probability.Conclusions:Prodromal PD markers are common in individuals with longstanding IRBD, suggesting that they are affected by an underlying neurodegenerative process. This observation may be useful for the design of disease-modifying trials to prevent PD onset in IRBD.

scholarly journals Impulse control disorders in Parkinson disease and RBD

Neurology ◽  
2019 ◽  
Vol 93 (7) ◽  
pp. e675-e687 ◽  
Author(s):  
Fahd Baig ◽  
Mark J. Kelly ◽  
Michael A. Lawton ◽  
Claudio Ruffmann ◽  
Michal Rolinski ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Multiple Imputation ◽  
Impulse Control ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Impulse Control Disorders ◽  
Semistructured Interview ◽  
Control Scale ◽  
Sleep Behavior

ObjectiveTo describe the prevalence, natural history, and risk factors for impulse control behaviors (ICBs) among people with Parkinson disease (PD), those with REM sleep behavior disorder (RBD), and controls.MethodsParticipants with early PD (within 3.5 years of diagnosis), those with RBD, and controls were clinically phenotyped and screened for ICBs longitudinally (with the Questionnaire for Impulsivity in Parkinson's Disease). ICB-positive individuals were invited for a semistructured interview, repeated 1 year later. The severity of the ICB was assessed with the Parkinson's Impulse Control Scale. Multiple imputation and regression models were used to estimate ICB prevalence and associations.ResultsData from 921 cases of PD at baseline, 768 cases at 18 months, and 531 cases at 36 months were included, with 21% to 25% screening positive for ICBs at each visit. Interviews of ICB screen–positive individuals revealed that 10% met formal criteria for impulse control disorders (ICD), while 33% had subsyndromal ICD (ICB symptoms without reaching the formal diagnostic criteria for ICD). When these data were combined through the use of multiple imputation, the prevalence of PD-ICB was estimated at 19.1% (95% confidence interval 10.1–28.2). On follow-up, 24% of cases of subsyndromal ICD had developed full symptoms of an ICD. PD-ICD was associated with dopamine agonist use, motor complications, and apathy but not PD-RBD. ICD prevalence in the RBD group (1%) was similar to that in controls (0.7%).ConclusionsICBs occur in 19.1% of patients with early PD, many persisting or worsening over time. RBD is not associated with increased ICD risk. Psychosocial drivers, including mood and support networks, affect severity.

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

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 &lt; 0.01), MDS-UPDRS total score progressed 3.98 points per year faster (p &lt; 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 &lt; 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.

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

Neurology ◽  
2018 ◽  
Vol 90 (18) ◽  
pp. e1618-e1626 ◽  
Author(s):  
Matthew J. Barrett ◽  
Jamie C. Blair ◽  
Scott A. Sperling ◽  
Mark E. Smolkin ◽  
T. Jason Druzgal
Keyword(s):  
Logistic Regression ◽  
Parkinson Disease ◽  
Rating Scale ◽  
Rem Sleep Behavior Disorder ◽  
Symptom Burden ◽  
Psychotic Symptoms ◽  
Sleep Behavior ◽  
Autonomic Symptoms ◽  
Increased Risk ◽  
Age And Sex

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.

scholarly journals A predictive model to identify Parkinson disease from administrative claims data

Neurology ◽  
2017 ◽  
Vol 89 (14) ◽  
pp. 1448-1456 ◽  
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.

Gamma Knife Thalamotomy for Parkinson Disease and Essential Tremor: A Prospective Multicenter Study

Neurosurgery ◽  
2011 ◽  
Vol 70 (3) ◽  
pp. 526-536 ◽  
Author(s):  
Chihiro Ohye ◽  
Yoshinori Higuchi ◽  
Toru Shibazaki ◽  
Takao Hashimoto ◽  
Toru Koyama ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Essential Tremor ◽  
Gamma Knife ◽  
Rating Scale ◽  
Spherical Shape ◽  
High Signal ◽  
Lateral Part ◽  
Thalamic Lesion ◽  
Clinical Effects

Abstract BACKGROUND: No prospective study of gamma knife thalamotomy for intractable tremor has previously been reported. Objective: To clarify the safety and optimally effective conditions for performing unilateral gamma knife (GK) thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a systematic postirradiation 24-month follow-up study was conducted at 6 institutions. We present the results of this multicenter collaborative trial. Methods: In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13) were registered at 6 Japanese institutions. Following our selective thalamotomy procedure, the lateral part of the ventralis intermedius nucleus, 45% of the thalamic length from the anterior tip, was selected as the GK isocenter. A single 130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological examination, magnetic resonance imaging and/or computerized tomography, the unified Parkinson's disease rating scale (UPDRS), electromyography, medication change, and video observations. Results: Final clinical effects were favorable. Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts II and III). Thalamic lesion size fluctuated but converged to either an almost spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high-signal zone (10.9%). No permanent clinical complications were observed. Conclusion: GK thalamotomy is an alternative treatment for intractable tremors of PD as well as for ET. Less invasive intervention may be beneficial to patients.

scholarly journals Physical activity and prodromal features of Parkinson disease

Neurology ◽  
2019 ◽  
Vol 93 (23) ◽  
pp. e2157-e2169 ◽  
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.

scholarly journals Minor hallucinations in Parkinson disease

Neurology ◽  
2019 ◽  
Vol 93 (6) ◽  
pp. 259-266 ◽  
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.

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