Impulse control disorders and use of dopamine agonists in early onset Parkinson's disease.

Introduction: Impulse control disorders (ICDs) are defined as excessive and repetitive behaviors that may affect Parkinson's disease (PD) patients exposed to dopamine agonists. Current data on ICDs in patients with early-onset Parkinson's disease (EOPD) is lacking. In this study we aim to assess the frequency of use of dopamine agonists, the prevalence of ICDs, and to explore potential factors associated with their development in patients with EOPD. Methods: We used the Mayo Clinic Data Explorer system to investigate a population-based cohort of EOPD patients between 1990 and 2022 at Mayo Clinic, Rochester, MN. We used ICD coding for parkinsonism; then, we reviewed all the clinical records and included only those patients with a clinical diagnosis of PD with symptoms onset at or before the age of 50, and who developed ICDs after using therapeutic doses of dopamine agonists. Results: A total of 831 (513 males and 318 females) patients with EOPD were included with a median age at symptom onset of 42 years of age (CI: 37-46). Dopamine agonists were used in 49.7% of all patients; of these, only 14.5% developed symptoms of one or more ICDs. Hypersexuality was the most commonly observed ICD (38.3%), and the only one having a statistically significant male predominance (p = 0.011). Conclusion: ICDs are common in EOPD, particularly when associated with the use of dopamine agonists.

Risk of hospitalization in synucleinopathies and impact of psychosis.

Background: Few studies have investigated the risk of hospitalization among patients with synucleinopathies (Parkinson disease, Dementia with Lewy Bodies, Parkinson disease dementia, Multiple System Atrophy) with associated psychosis and the impact of antipsychotic treatments on hospital admissions and duration of the stay. Objective: To determine the risk of hospitalization among patients with synucleinopathies and in patients with associated psychosis. To evaluate the impact of antipsychotic treatments on hospital admission of patients with synucleinopathies and psychosis in an incident cohort study in Olmsted County, Minnesota (MN). Methods: We used the Rochester Epidemiology Project (REP) to define an incident cohort of patients with clinically diagnosed synucleinopathies (1991-2010) in Olmsted County, MN. A movement disorder specialist reviewed all medical records to confirm the clinical diagnosis of synucleinopathies using the NINDS/NIMH unified diagnostic criteria. Results: We included 416 incident cases of clinically diagnosed synucleinopathies from 2,669 hospitalizations. 409 patients (98.3%) were admitted to the hospital at least once for any cause after the onset of parkinsonism. The median number of hospitalizations for a single patient was 5. In total, 195 (46.9%) patients met the criteria for psychosis: patients with psychosis had a 49% (HR = 1.49, p < 0.01) increased risk of hospitalization compared to patients without psychosis. Among patients with psychosis, 76 (39%) received antipsychotic medication. Treatment with antipsychotic medications did not affect the risk of hospitalization (HR = 0.93, p = 0.65). The median length of hospitalization among the entire cohort was 1 (IQR 0-4) day. There was no difference between hospitalization length for patients with no psychosis and patients with active psychosis (RR = 1.08, p = 0.43) or patients with resolved psychosis (RR = 0.79, p = 0.24). Conclusion: Psychosis increases the risk of hospitalization in patients with clinically defined synucleinopathies; however, it does not affect the length of hospital stays in our cohort. Antipsychotic treatment does not affect the risk of hospitalization in our study.

Sleep Disorders in Early-Onset Parkinsonism: A Population-Based Study.

BACKGROUND: Sleep disturbances are common in parkinsonian disorders; however, whether sleep disorders affect individuals with early-onset parkinsonism and whether they differ from individuals with typical-onset parkinsonism is unknown. OBJECTIVE: To compare the prevalence and incidence of sleep disorders before and after parkinsonian motor symptom onset between individuals with early onset parkinsonism (age ≤50 at motor symptom onset) and typical-onset parkinsonism (age >50 at motor symptom onset). METHODS: We used a population-based, 1991 to 2015 incident-cohort study of parkinsonism including 38 patients with early-onset and 1,001 patients with typical-onset parkinsonism. Presence or absence and type of sleep disorder as well as the relationship between motor and sleep symptoms were abstracted from the medical records. Rates of sleep disorders before and after onset of parkinsonism were compared with logistic regression and Cox proportional hazards models. RESULTS: The prevalence of sleep disorders prior to the onset of parkinsonism in early vs. typical parkinsonism (24% vs. 16% p = 0.19) and incidence of sleep disorders after parkinsonism onset (5.85 cases per 100 person-years vs. 4.11 cases per 100 person-years; HR 1.15 95% CI: 0.74-1.77) were similar between the two groups. Early-onset parkinsonism had a higher risk for developing post-motor insomnia compared with typical-onset parkinsonism (HR 1.73, 95% CI: 1.02-2.93); the risk for developing all other sleep disorders considered was similar between groups. CONCLUSION: Sleep disorders are common in individuals with early-onset parkinsonism and occur with similar frequency to those with typical-onset parkinsonism, except for insomnia, which was more frequent in the early-onset group.

40-Year Incidence of Early-Onset Parkinson's Disease in Southeast Minnesota.

BACKGROUND: Parkinson's disease (PD) most commonly surfaces at middle age. An earlier onset is named early-onset Parkinson's disease (EOPD), but the exact definition is a matter of ongoing scientific debate. OBJECTIVE: To investigate 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, Minnesota. METHODS: We used the Rochester Epidemiology Project (REP) to identify all incident EOPD cases in Olmsted County, 1976-2015. A movement-disorder specialist reviewed all cases to confirm the EOPD diagnosis. For EOPD definition, we used two age cut-offs: motor-symptom onset at or before 50 and 55 years. RESULTS: EOPD incidence was 1.43/100,000 person-years for ≤55 and 0.55/100,000 for ≤50 years. Men had a higher incidence in both groups [1.84 vs. 1.03 (p = 0.04); and 0.70 vs. 0.40 (p = 0.24), respectively]. EOPD incidence of patients with motor-symptom onset before age 55 increased from 1.02/100.000 person-year 1976-1985, to 1.32/100.000 person-year 2006-2015. A similar trend was observed when ≤50 years cut-off was used (0.28/100,000 person-years 1976-1985, to 0.59/100,000 person-year 2006-2015). However, negative binomial regression found no significant change in incidence per 10 years (RR = 1.04 and 1.24 in the two groups). Incidence was consistently higher in men than women. Median time from EOPD-symptom onset to death was shorter in the EOPD ≤55 group (21.9 years) compared to the EOPD ≤50 group (25.6 years). CONCLUSION: We observed an increased trend in the incidence of EOPD with both cut-off ages. Overall, incidence of EOPD was 1.43 (≤55) and 0.55 (≤50) cases per 100,000 person-years, higher in men.

Subjective Sleep Quality as it Relates to Cognitive and Physical Function in Spinal Muscular Atrophy Patients.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA (n = 21) patients and age-matched controls (n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery. Further, we investigated the association between clinical functional scores and sleep questionnaire scores. Among SMA patients, better motor and limb function was associated with better subjective sleep quality (p's< 0.05). Clinicians should consider sleep quality in patient care and future studies are needed to better understand these relationships.

Lifelong constipation in Parkinson's disease and other clinically defined alpha-synucleinopathies: A population-based study in Southeast Minnesota.

INTRODUCTION: Epidemiological studies show correlations between constipation and development of Parkinson's disease (PD); however, few studies have explored the association between constipation and dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and multiple system atrophy (MSA). We sought to explore the lifelong association of constipation and PD, DLB, PDD, and MSA (α-Synucleinopathies), compared to age- and sex-matched controls. METHODS: Using the Rochester Epidemiology Project (REP), we established an incident cohort of clinically defined α-synucleinopathies. A movement-disorder specialist reviewed all medical charts to establish clinical diagnoses. RESULTS: We identified 453 incident cases of clinically diagnosed α-synucleinopathies and an identical number of age- and sex-matched controls in Olmsted County (MN), 1991-2010. There were 303 cases of PD; 80, DLB; 54, PDD; and 16, MSA. Approximately 50% of α-synucleinopathies of all types reported constipation, compared to 27% in controls. The earliest pre-motor onset constipation was in DLB (median, 3.76 years prior to α-synucleinopathies motor-symptom onset); latest onset post-motor constipation was in PD (median, 5.15 years after motor-symptom onset). PD also had the highest longstanding constipation rate (18.2%). All α-synucleinopathies had higher odds of constipation compared to controls, except for MSA (p = 0.09), likely due to a limited sample size. CONCLUSION: PD, DLB, and PDD had higher odds of constipation compared to controls; PD had the most widespread onset of lifelong constipation, both longstanding and pre- or post-motor onset symptoms. Our results indicate that constipation rates do not differ among α-synucleinopathies but do differ in terms of temporal onset compared to disease onset.

Withdrawal notice to "40-Year incidence of early-onset Parkinson's disease (EOPD) in Southeast Minnesota" [Park. Relat. Disord. 104 (2022) 64-67].

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at (https://www.elsevier.com/about/policies/article-withdrawal).

Early-Onset Parkinson's Disease: Creating the Right Environment for a Genetic Disorder.

Parkinson's disease (PD) by its common understanding is a late-onset sporadic movement disorder. However, there is a need to recognize not only the fact that PD pathogenesis expands beyond (or perhaps to) the brain but also that many early-onset patients develop motor signs before the age of 50 years. Indeed, studies have shown that it is likely the protein aggregation observed in the brains of patients with PD precedes the motor symptoms by perhaps a decade. Studies on early-onset forms of PD have shown it to be a heterogeneous disease with multiple genetic and environmental factors determining risk of different forms of disease. Genetic and neuropathological evidence suggests that there are α-synuclein centric forms (e.g., SNCA genomic triplication), and forms that are driven by a breakdown in mitochondrial function and specifically in the process of mitophagy and clearance of damaged mitochondria (e.g., PARKIN and PINK1 recessive loss-of-function mutations). Aligning genetic forms with recognized environmental influences will help better define patients, aid prognosis, and hopefully lead to more accurately targeted clinical trial design. Work is now needed to understand the cross-talk between these two pathomechanisms and determine a sense of independence, it is noted that autopsies studies for both have shown the presence or absence of α-synuclein aggregation. The integration of genetic and environmental data is critical to understand the etiology of early-onset forms of PD and determine how the different pathomechanisms crosstalk.

40-Year incidence of early-onset Parkinson's disease (EOPD) in Southeast Minnesota.

INTRODUCTION: Parkinson's disease (PD) most commonly surfaces at middle age. Earlier onset is characterized as Early-onset Parkinson's disease (EOPD), but the exact definition has been a matter of ongoing scientific debate. We investigated 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, MN. METHODS: We used the Rochester Epidemiology Project (REP) to identify all incident EOPD cases in Olmsted County between 1976 and 2015. A movement-disorder specialist reviewed all cases to confirm the EOPD diagnosis. For EOPD definition, we used two age cut-offs: 50 and 55 years. RESULTS: EOPD incidence was 1.43/100,000 person-years for ≤55 and 0.55/100,000 for ≤50 years. Men had a higher incidence than women in both groups [1.84 vs 1.03 (p = 0.04); and 0.70 vs 0.40 (p = 0.24), respectively]. EOPD incidence diagnosed before age 55 increased each decade: from 1.02/100.000 person-year 1976-1985, to 1.32/100.000 person-year 2006-2015. A similar trend was observed when ≤50 years of age cut off was used (0.28/100,000 person-years 1976-1985, to 0.59/100,000 person-year 2006-2015). Incidence was consistently higher in men than women. Median time from EOPD-symptoms onset to death was shorter in the EOPD ≤55 group (21.9 years) compared to the EOPD ≤50 group (25.6 years). CONCLUSION: We observed an increased trend in the incidence of EOPD, both in ≤55 and ≤ 50 years of age. Overall, incidence of EOPD was 1.43 (≤55) and 0.55 (≤50) cases per 100,000 person-years, and although not significant, was higher in men than in women.

Life after autoantibody-mediated encephalitis: optimizing follow-up and management in recovering patients.

PURPOSE OF REVIEW: Timely diagnosis and treatment is essential to optimize outcomes in patients with antibody-mediated encephalitis (AME); yet even with early diagnosis and treatment, long-term outcomes may still fall short of expectations. Identifying patients at greater risk of adverse outcomes is key to personalizing care, supporting accurate counseling of patients and family members, and informing therapeutic decisions in patients with AME. This review considers long-term outcomes in recovering patients, including approaches to measure and manage common sequelae that influence life after AME. RECENT FINDINGS: Cognitive impairment, fatigue, and sleep disturbances affect most recovering AME patients. This realization highlights the need for outcome measures that encompass more than motor function. Standardized questionnaires, surveys, and clinical assessment tools may be adapted to support comprehensive and reproducible clinical assessments and to identify patients who may benefit from additional therapies. SUMMARY: Good outcomes continue to be reported in recovering patients, emphasizing the high potential for recovery following AME. However, cognitive, behavioral, and physical sequelae may limit the potential for great outcomes following AME. Multidisciplinary follow-up is needed to recognize and treat sequelae that compromise long-term recovery and limit quality of life in recovering patients.

Traumatic Brain Injury and Risk of Alzheimer's Disease and Related Dementias in the Population.

BACKGROUND: Epidemiological studies examining associations between traumatic brain injury (TBI) and Alzheimer's disease and related dementias (ADRD) have yielded conflicting results, which may be due to methodological differences. OBJECTIVE: To examine the relationship between the presence and severity of TBI and risk of ADRD using a population-based cohort with medical record abstraction for confirmation of TBI and ADRD. METHODS: All TBI events among Olmsted County, Minnesota residents aged > 40 years from 1985-1999 were confirmed by manual review and classified by severity. Each TBI case was randomly matched to two age-, sex-, and non-head injury population-based referents without TBI. For TBI events with non-head trauma, the Trauma Mortality Prediction Model was applied to assign an overall measure of non-head injury severity and corresponding referents were matched on this variable. Medical records were manually abstracted to confirm ADRD diagnosis. Cox proportional hazards models examined the relationship between TBI and severity with risk of ADRD. RESULTS: A total of 1,418 residents had a confirmed TBI (865 Possible, 450 Probable, and 103 Definite) and were matched to 2,836 referents. When combining all TBI severities, the risk of any ADRD was significantly higher for those with a confirmed TBI compared to referents (HR = 1.32, 95% CI: 1.11, 1.58). Stratifying by TBI severity, Probable (HR = 1.42, 95% CI: 1.05, 1.92) and Possible (HR = 1.29, 95% CI: 1.02-1.62) TBI was associated with an increased risk of ADRD, but not Definite TBI (HR = 1.22, 95% CI: 0.68, 2.18). CONCLUSION: Our analyses support including TBI as a potential risk factor for developing ADRD.

Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study.

Cognitive abilities are often affected in progressive neurodegenerative disorders, but there is a lack of understanding about whether spinal muscular atrophy (SMA) patients experience cognitive deficits and, if so, whether they are associated with clinical factors. A sample of 22 type III SMA patients and 22 healthy controls completed a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning. Clinical severity was assessed using the Hammersmith Functional Motor Scale, the Revised Upper Limb Module and the Six Minute Walk Test. SMA patients showed poorer performance in visuospatial abilities, executive functions and language as compared to healthy controls. In the SMA sample, patients with greater motor difficulties had lower performance in attention, but higher performance in measures of language, verbal fluency, and memory. In men, but not women, cognitive test performance was associated with motor functioning. Our findings showing cognitive changes in SMA type III may reflect the presence of intrinsic brain pathology and cognitive adaptation mechanisms following physical dysfunction, which may be mediated by other factors, such as sex.

Incidence, Prevalence, and Mortality of Psychosis Associated with Parkinson's Disease (1991-2010).

BACKGROUND: Parkinson's disease (PD)-associated psychosis is a well-known non-motor complication, occurring years after diagnosis of PD. Incidence data vary across different studies highlighting a need for long-term observation and clinical definition. OBJECTIVE: To determine the incidence of psychosis in patients with PD and to investigate their survival in an incident cohort study from 1991-2010 in Olmsted County, MN. METHODS: We used the Rochester Epidemiology Project to define an incident-cohort study of parkinsonism (1991-2010) in Olmsted County, MN. A movement-disorder specialist reviewed the electronic medical records and applied diagnosis criteria to PD. Psychosis was diagnosed using of NINDS/NIMH unified criteria. RESULTS: We identified 669 cases of parkinsonism; 297 patients were clinically diagnosed with PD. 114/297 (38.4%) patients had evidence of psychosis (60% male); the median onset age of psychosis was 79.4 years. The incidence of Parkinson's disease psychosis (PDP) was 4.28/100 person-years. PDP patients had a 71% increased risk of death compared to PD patients. In PD patients without psychosis, men had 73.4% increased risk of death compared to women, whereas no significant sex difference was observed among PDP men vs. women. Of 114 patients diagnosed with psychosis, 59 were treated with antipsychotics. There was no significant difference in survival between treated and untreated patients. CONCLUSION: PDP increased the odds of death compared to PD patients. Men with PD without psychosis had greater odds of death compared to women; however, in PD with psychosis the odds of death were comparable among sexes. Lastly, treatment with anti-psychotics did not significantly affect survival.

Deep Brain Stimulation and Treatment Outcomes of Young- and Late-Onset (≤55 Years) Parkinson's Disease: A Population-Based Study.

Background: No studies have reported the rate of motor complications (MC) and response to medical and surgical treatment in a population-based cohort of young-onset Parkinson's Disease (YOPD) patients and a cohort of sex-matched late-onset Parkinson's Disease (LOPD). Objective: To assess the outcomes of dopaminergic treatment in YOPD and LOPD, explore treatment-induced MC, medical adjustment, and rate of deep brain stimulation (DBS). Methods: We used the expanded Rochester Epidemiology Project (eREP) to investigate a population-based cohort of YOPD between 2010 and 2015 in 7 counties in Minnesota. Cases with onset ≤55 years of age were included as YOPD. An additional sex-matched cohort of LOPD (onset at ≥56 years of age) was included for comparison. All medical records were reviewed to confirm the diagnoses. Results: In the seven counties 2010-15, there were 28 YOPD patients, which were matched with a LOPD cohort. Sixteen (57%) YOPD had MC, as compared to 9 (32%) LOPD. In YOPD, 9 had motor fluctuations (MF) and Levodopa-induced dyskinesia (LID) together, whereas 3 had LID only and 4 MF only. In LOPD, 3 had MF and LID, 3 MF only, and 3 LID only. Following medical treatment for MC, 6/16 YOPD (38%) and 3/9 (33%) LOPD had symptoms resolution. In YOPD, 11/16 (69%) were considered for DBS implantation, in LOPD they were 2/9 (22%), but only 7 (6 YOPD and 1 LOPD) underwent the procedure. YOPD had significantly higher rates in both DBS candidacy and DBS surgery (respectively, p = 0.03 and p = 0.04). Among DBS-YOPD, 5/6 (83%) had positive motor response to the surgery; the LOPD case had a poor response. We report the population-based incidence of both YOPD with motor complications and YOPD undergoing DBS, which were 1.17 and 0.44 cases per 100,000 person-years, respectively. Conclusion: Fifty-seven percent of our YOPD patients and 32% of the LOPD had motor complications. Roughly half of both YOPD and LOPD were treatment resistant. YOPD had higher rates of DBS candidacy and surgery. Six YOPD and 1 LOPD underwent DBS implantation and most of them had a positive motor response after the surgery.

Early-Onset Parkinsonism and Early-Onset Parkinson's Disease: A Population-Based Study (2010-2015).

BACKGROUND: Early-onset Parkinson's disease (EOPD), occurring between ages 40 and 55, carries social, societal, and personal consequences and may progress, with fewer comorbidities than typical, later-onset disease. OBJECTIVE: To examine the incidence and survival of EOPD and other Parkinsonism occurring before age 55 in the population-based cohort of residents in seven Minnesota counties. METHODS: A movement-disorder specialist reviewed all the medical records in a 2010-2015 Parkinsonism-incident cohort to confirm diagnosis and subtypes. RESULTS: We identified 27 patients diagnosed at ≤ 50 years with incident Parkinsonism 2010-15:11 (41%) cases of EOPD, 13 (48%) drug-induced Parkinsonism, and 3 (11%) other Parkinsonism; we also identified 69 incident cases of Parkinsonism ≤ 55 years, of which 28 (41%) were EOPD, 28 (41%) DIP, and 13 (19%) other Parkinsonism. Overall incidence for Parkinsonism ≤ 50 years was 1.98/100,000 person-years, and for EOPD was 0.81/100,000 person-years. In patients ≤ 55 years, Parkinsonism incidence was 5.05/100,000 person-years: in EOPD, 2.05/100,000 person-years. Levodopa-induced dyskinesia was present in 45%of EOPD (both ≤ 50 years and ≤ 55 years). Onset of cardinal motor symptoms was proximate to the diagnosis of EOPD, except for impaired postural reflexes, which occurred later in the course of EOPD. Among the 69 Parkinsonism cases ≤ 55 years, 9 (13%; all male) were deceased (only 1 case of EOPD). Men had a higher mortality risk compared to women (p = 0.049). CONCLUSION: The incidence of EOPD ≤ 50 years was 0.81/100,000 person-years (1.98 in Parkinsonism all type); prior to ≤ 55 years was 2.05/100,000 person-years (5.05 in Parkinsonism all type) with higher incidence in men than women. Men with Parkinsonism, all type, had higher mortality compared to women.

Timeline of Rapid Eye Movement Sleep Behavior Disorder in Overt Alpha-Synucleinopathies.

OBJECTIVE: The aim was to analyze the timeline, prevalence, and survival of rapid eye movement (REM) sleep behavior disorder (RBD) in patients who developed alpha-synucleinopathies (Parkinson disease, dementia with Lewy bodies, and Parkinson disease dementia) compared with age- and sex-matched controls in a population-based incident-cohort study. METHODS: We used a population-based, 1991 to 2010 incident-cohort study of alpha-synucleinopathies. A movement-disorder specialist reviewed medical records to confirm diagnoses. RBD was diagnosed by reported dream-enactment symptoms or polysomnography. Probable RBD and polysomnographically confirmed RBD were analyzed separately and combined. RESULTS: Among the 444 incident cases of alpha-synucleinopathy, 86 were clinically diagnosed with RBD (19.8%), including 30 (35%) by polysomnography and 56 (65%) as probable. The prevalence of idiopathic RBD at alpha-synucleinopathy diagnosis was 3.4%, increasing to 23.8% after 15 years. Cumulative lifetime incidence was 53 times greater in alpha-synucleinopathy patients than in controls (odds ratio [OR] = 53.1, 95% confidence interval [CI]: 13.0-217.2, p < 0.0001), higher in dementia with Lewy bodies than in Parkinson disease (OR = 2.57, 95% CI: 1.50-4.40, p = 0.0004), and higher in men than in women with Parkinson disease, dementia with Lewy bodies, or Parkinson disease dementia (OR = 3.70, 95% CI: 2.07-6.62, p < 0.0001), but did not increase mortality risk. INTERPRETATION: Our cohort had RBD incidence of 3.4%. Overall RBD increased to 23.8% after 15 years, with an overall incidence of 2.5 cases per 100 person-years. With 53 times greater lifetime incidence in alpha-synucleinopathy patients than in controls, RBD was more likely to develop in dementia with Lewy bodies than in Parkinson disease or Parkinson disease dementia, and in men than in women, but did not increase mortality risk within our cohort. ANN NEUROL 2021;89:293-303.

Sex differences in movement disorders.

A number of studies reported the possible differences between men and women in movement disorders. Evidence shows that estrogens may have a neuroprotective effect and may modulate the neurodevelopment of the different brain structures. Movement disorders including Parkinson's disease, dementia with Lewy body, Huntington's disease, Tourette's syndrome, and dystonia among others display significant clinical differences between sexes, with structural differences in the dopaminergic pathways between men and women. Here we summarize the most relevant clinical aspects of some of the most common movement disorders, highlighting the differences in disease onset, clinical presentation, therapy, and outcomes. Increased recognition of these differences may help physicians better understand the pathophysiology of these conditions and provide a tailored therapeutic approach.

Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications.

OBJECTIVE: We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson's disease (PD). METHODS: Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD. RESULTS: At onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old). CONCLUSIONS: Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.

Infections or Sepsis Preceding Clinically Diagnosed α-Synucleinopathies: A Case-Control Study.

BACKGROUND: Several studies have proposed a role for infections to induce an inflammatory response triggering Parkinson's disease. This remains controversial and the influence of severe infections on other α-synucleinopathies (Dementia with Lewy Bodies, Parkinson's disease dementia, and Multiple System Atrophy) has not been adequately investigated. OBJECTIVES: To assess the association between hospitalization-required infections or sepsis and risk of clinically diagnosed α-synucleinopathies. METHODS: Using the medical records-linkage system (Rochester Epidemiology Project), we identified all α-synucleinopathy cases of in Olmsted County (1991-2010). Cases were matched by symptom-onset age and sex to controls. We reviewed complete medical records to detect hospital-required infections or sepsis preceding clinical-motor onset of α-synucleinopathies. We used conditional logistic regression to calculate the odds ratio of all α-synucleinopathies, adjusting for medications, coffee, and smoking. RESULTS: There was no association between infection-related hospitalization (odds ratio: 1.05; 95% confidence interval: 0.78-1.40; P = 0.76) or sepsis (odds ratio: 0.86; 95% confidence interval: 0.40-1.85; P = 0.70) and all α-synucleinopathies in multivariable analyses. We did not identify any associations after stratifying for type of α-synucleinopathy, sex, and age at clinical-motor onset. We analyzed sepsis separately with similar results. CONCLUSION: We did not observe any associations between infections leading to hospitalization or sepsis and development of any α-synucleinopathies. © 2020 International Parkinson and Movement Disorder Society.