Early-onset Parkinson's Disease Research Articles

Early-onset and late-onset Parkinson's disease exhibit a different profile of gait and posture features based on the Kinect.

Gait and posture abnormalities are the common disabling motor symptoms in Parkinson's disease (PD). This study aims to investigate the differential characteristics of gait and posture in early-onset PD (EOPD) and late-onset PD (LOPD) using the Kinect depth camera. Eighty-eight participants, including two subgroups of 22 PD patients and two subgroups of 22 healthy controls (HC) matched for age, sex, and height, were enrolled. Gait and posture features were quantitatively assessed using a Kinect-based system. A two-way analysis of variance was used to compare the difference between different subgroups. EOPD had a significantly higher Gait score than LOPD (p = 0.031). Specifically, decreased swing phase (p = 0.034) was observed in the EOPD group. Although the Posture score was similar between the two groups, LOPD was characterized by an increased forward flexion angle of the trunk at the thorax (p = 0.042) and a decreased forward flexion angle of the head relative to the trunk (p = 0.009). Additionally, age-independent features were observed in both PD subgroups, and post hoc tests revealed that EOPD generally performed worse gait features. In comparison, LOPD was characterized by worse performance in posture features. EOPD and LOPD exhibit different profiles of gait and posture features. The phenotype-specific characteristics likely reflect the distinct neurodegenerative processes between them.

Diagnostic utility of whole-exome sequencing in early onset and familial Parkinson's disease: Preliminary findings in a regional centre study

Diagnostic utility of whole-exome sequencing in early onset and familial Parkinson's disease: Preliminary findings in a regional centre study

Evaluation of the role of FMR1 CGG repeat allele in Parkinson's disease from the Chinese population.

There is controversial evidence that FMR1 premutation or "gray zone" (GZ) allele (small CGG expansion, 45-54 repeats) was associated with Parkinson's disease (PD). We aimed to explore further the association between FMR1 CGG repeat expansions and PD in a large sample of Chinese origin. We included a cohort of 2,362 PD patients and 1,072 controls from the Parkinson's Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) in this study and conducted repeat-primed polymerase chain reaction (RP-PCR) for the size of FMR1 CGG repeat expansions. Two PD patients were detected with FMR1 premutation (61 and 56 repeats), and the other eleven PD patients were detected with the GZ allele of FMR1 CGG repeat expansions. Those thirteen PD patients responded well to levodopa and were diagnosed with clinically established PD. Specifically, one female PD patient with GZ allele was also found with premature ovarian failure. However, compared to healthy controls, we found no significant enrichment of GZ allele carriers in PD patients or other subgroups of PD cases, including the subgroups of female, male, early-onset, and late-onset PD patients. Furthermore, we did not find any correlation between the FMR1 gene CGG repeat sizes and age at onset of PD. It suggested that FMR1 premutation was related to PD, but the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in PD cases of Chinese origin. Further larger multiple ethnic studies are needed to determine further the role of the FMR1 GZ allele in PD.

Parkin regulates amino acid homeostasis at mitochondria-lysosome (M/L) contact sites in Parkinson's disease.

Mutations in the E3 ubiquitin ligase parkin are the most common cause of early-onset Parkinson's disease (PD). Although parkin modulates mitochondrial and endolysosomal homeostasis during cellular stress, whether parkin regulates mitochondrial and lysosomal cross-talk under physiologic conditions remains unresolved. Using transcriptomics, metabolomics and super-resolution microscopy, we identify amino acid metabolism as a disrupted pathway in iPSC-derived dopaminergic neurons from patients with parkin PD. Compared to isogenic controls, parkin mutant neurons exhibit decreased mitochondria-lysosome contacts via destabilization of active Rab7. Subcellular metabolomics in parkin mutant neurons reveals amino acid accumulation in lysosomes and their deficiency in mitochondria. Knockdown of the Rab7 GTPase-activating protein TBC1D15 restores mitochondria-lysosome tethering and ameliorates cellular and subcellular amino acid profiles in parkin mutant neurons. Our data thus uncover a function of parkin in promoting mitochondrial and lysosomal amino acid homeostasis through stabilization of mitochondria-lysosome contacts and suggest that modulation of interorganelle contacts may serve as a potential target for ameliorating amino acid dyshomeostasis in disease.

CD33 polymorphisms and Parkinson’s disease Parkinson’s disease in northern Chinese Han population: A case-control study

ObjectiveParkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33’s role as a critical immunoregulatory receptor in neuroinflammatory responses. MethodsThe present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). ResultsAlleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people. ConclusionThis study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD.

Loss of STING in parkin mutant flies suppresses muscle defects and mitochondria damage.

The early pathogenesis and underlying molecular causes of motor neuron degeneration in Parkinson's Disease (PD) remains unresolved. In the model organism Drosophila melanogaster, loss of the early-onset PD gene parkin (the ortholog of human PRKN) results in impaired climbing ability, damage to the indirect flight muscles, and mitochondrial fragmentation with swelling. These stressed mitochondria have been proposed to activate innate immune pathways through release of damage associated molecular patterns (DAMPs). Parkin-mediated mitophagy is hypothesized to suppress mitochondrial damage and subsequent activation of the cGAS/STING innate immunity pathway, but the relevance of this interaction in the fly remains unresolved. Using a combination of genetics, immunoassays, and RNA sequencing, we investigated a potential role for STING in the onset of parkin-null phenotypes. Our findings demonstrate that loss of Drosophila STING in flies rescues the thorax muscle defects and the climbing ability of parkin-/- mutants. Loss of STING also suppresses the disrupted mitochondrial morphology in parkin-/- flight muscles, suggesting unexpected feedback of STING on mitochondria integrity or activation of a compensatory mitochondrial pathway. In the animals lacking both parkin and sting, PINK1 is activated and cell death pathways are suppressed. These findings support a unique, non-canonical role for Drosophila STING in the cellular and organismal response to mitochondria stress.

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson's disease.

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease. A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated. The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05). 11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

Antiparkinsonian effects of Indian spice Amomum subulatum fruit extract by modulating the behavioural, inflammatory markers, antioxidant, and histopathology parameters in rats

Parkinson's disease (PD) is a complex neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra followed by dopamine depletion in the striatum. PD usually affects people over 50; when those under 50 are involved, it is generally referred to as early-onset PD. The present study aimed to understand and explain the role of the typical Indian spice, greater cardamom, against parkinsonism and related complications. The methanolic extract of Amomum subulatum has flavonoids as the major phytoconstituent and may be a beneficial adjuvant in treating PD. Amomum subulatum fruit extract (ASFE) was given as treatment to the rats at 100 mg/kg and 200 mg/kg. Symptoms of Parkinson’s disease, such as tremors, muscular rigidity, catalepsy, locomotor activity, and grip strength, were examined by several behavioural tests. Treatment with ASFE showed a significant decrease in all the symptoms of PD. Enzyme assays revealed a reduction in the levels of antioxidant enzymes SOD, Catalase, and GSH after administering reserpine and increased levels after treating ASFE. ASFE causes dopaminergic neuron regeneration after reserpine induces injury, thus increasing dopamine levels and restoring cellular damage. The inflammatory biomarkers revealed decreased proinflammatory cytokines such as TNF-α and IL-6. In contrast, increase in the level of IL-10, which is an anti-inflammatory cytokine. The histopath studies showed reduced cell damage occurring in PD after the treatment with ASFE. The present investigation highlights the role of greater cardamom from the Indian kitchen to ethnopharmacology in progressive neurological degeneration.

Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson's disease.

Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson's disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD. Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls. We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

People with Early Onset Parkinson's Disease: Empowered to Improve Care.

Patient organizations play an ever-growing role in modern societies by providing organized resources for patients and care partners. Importantly, patient organizations enable patients to define and share their needs and views. In Parkinson's disease (PD), patient organizations play significant roles in different countries. However, there is limited support and resources tailored for people with early onset Parkinson's disease (EOPD). These individuals face unique social, professional, and personal challenges that are often not accounted for by general PD organizations, which play very important roles for a significant proportion of individuals with PD. In Portugal, this was the situation until 2022, when Young Parkies Portugal (YPP) was founded to allow people with EOPD and various stakeholders to join forces to cover their specific needs. In this manuscript, we aim to share our experience in building an association for people with EOPD, reflecting on the reasons for this need, the activities developed thus far, challenges in implementation, and future directions. In summary, we believe that nonprofit organizations like YPP play an essential role in shaping the care and support of people with PD care and should be considered key partners of care alongside the larger multidisciplinary team. We are confident that sharing our experience can inspire and guide the implementation of similar initiatives in other countries.

A systematic analysis of genotype–phenotype associations with PLA2G6

BackgroundPLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP). ObjectivesTo determine the genotype–phenotype association in PLAN. Methods“PLA2G6” or “PARK14” or “phospholipase A2 group VI” or “iPLA2β” were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment. ResultsThe loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025). ConclusionsLOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.

PINK1-Dependent Mitophagy Inhibits Elevated Ubiquitin Phosphorylation Caused by Mitochondrial Damage.

Ubiquitin phosphorylation by the mitochondrial protein kinase PTEN-induced kinase 1 (PINK1), upon mitochondrial depolarization, is an important intermediate step in the recycling of damaged mitochondria via mitophagy. As mutations in PINK1 can cause early-onset Parkinson's disease (PD), there has been a growing interest in small-molecule activators of PINK1-mediated mitophagy as potential PD treatments. Herein, we show that N6-substituted adenosines, such as N6-(2-furanylmethyl)adenosine (known as kinetin riboside) and N6-benzyladenosine, activate PINK1 in HeLa cells and induce PINK1-dependent mitophagy in primary mouse fibroblasts. Interestingly, pre-treatment of HeLa cells and astrocytes with these compounds inhibited elevated ubiquitin phosphorylation that is induced by established mitochondrial depolarizing agents, carbonyl cyanide m-chlorophenyl-hydrazine and niclosamide. Together, this highlights N6-substituted adenosines as progenitor PINK1 activators that could potentially be developed, in the future, as treatments for aged and sporadic PD patients who have elevated phosphorylated ubiquitin levels in the brain.

Genetic analysis of dystonia-related genes in Parkinson's disease.

Parkinson's disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort. We comprehensively analyzed the rare variants of 47 known dystonia-related genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on different inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD. We found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes including COL6A3 and TH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S in ANO3, p.R678H in ADCY5, and p.R458Q in SLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups of TH, SQSTM1, THAP1, and ADCY5 in sporadic early-onset PD, whereas COL6A3 was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction. Our findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role of COL6A3 and TH genes in PD is highlighted.

The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China

So far, over 20 causative genes of monogenic Parkinson’s disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders.

Parkin Maintains Robust Pacemaking in Human Induced Pluripotent Stem Cell-Derived A9 Dopaminergic Neurons.

The degeneration of nigral (A9) dopaminergic (DA) neurons results in cardinal motor symptoms that define Parkinson's disease (PD). Loss-of-function mutations in parkin are linked to a rare form of early-onset PD that is inherited recessively. We generated isogenic human A9 DA neurons with or without parkin mutations to establish the causal relationship between parkin mutations and the dysfunction of human A9 DA neurons. Using TALEN (transcription activator-like effector nuclease)- or CRISPR/Cas9-mediated gene targeting, we produced two isogenic pairs of naivetropic induced pluripotent stem cells (iPSCs) by repairing exon 3 deletions of parkin in iPSCs derived from a PD patient and by introducing the PD-linked A82E mutation into iPSCs from a healthy subject. The four lines of isogenic iPSCs were differentiated to A9 DA neurons, which fired spontaneous pacemaking action potentials (AP) dependent on L-type Ca2+ channels. The frequency of the pacemaking APs was significantly reduced by parkin mutations introduced to normal neurons. Consistent with this, isogenic repair of parkin mutations significantly increased the frequency from that observed in patient-derived neurons. The results show that parkin maintains robust pacemaking in human iPSC-derived A9 DA neurons. The function is critical to normal DA transmission required for controlling voluntary locomotor activities. © 2023 International Parkinson and Movement Disorder Society.

PLA2G6-associated late-onset parkinsonism in a Sudanese family.

The phospholipase A2 group VI gene (PLA2G6) encodes an enzyme that catalyzes the hydrolytic release of fatty acids from phospholipids. Four neurological disorders with infantile, juvenile, or early adult-onset are associated with PLA2G6 genetic alterations, namely infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia-parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). Few studies in Africa reported PLA2G6-associated disorders and none with parkinsonism of late adult onset. The patients were clinically assessed following UK Brain Bank diagnostic criteria and International Parkinson and Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Brain MRI without contrast was performed. Genetic testing was done using a custom-made Twist panel, screening 34 known genes, 27 risk factors, and 8 candidate genes associated with parkinsonism. Filtered variants were PCR-amplified and validated using Sanger sequencing and also tested in additional family members to study their segregation. Two siblings born to consanguineous parents developed parkinsonism at the age of 58 and 60 years, respectively. MRI showed an enlarged right hippocampus in patient 2, but no overt abnormalities indicative of INAD or iron deposits. We found two heterozygous variants in PLA2G6, an in-frame deletion NM_003560:c.2070_2072del (p.Val691del) and a missense variant NM_003560:c.956C>T (p.Thr319Met). Both variants were classified as pathogenic. This is the first case in which PLA2G6 is associated with late-onset parkinsonism. Functional analysis is needed to confirm the dual effect of both variants on the structure and function of iPLA2β.

DJ-1 promotes cell migration by interacting with Mena, the mammalian homolog of Drosophila enabled.

DJ-1 has gained extensive attention after being identified in 2003 as a protein implicated in the pathogenesis of early-onset Parkinson's disease. Since then, efforts have revealed versatile DJ-1 functions in reactive oxygen species (ROS) control, transcriptional regulation, chaperone function, fertility, and cell transformation. Herein, we report a novel function of DJ-1 in actin cytoskeletal rearrangements. DJ-1 was identified as a new binding partner of Mena, a protein of the Enah/VASP family, and it promoted cancer cell migration by Mena-dependent actin polymerization and filopodia formation. These results suggest a novel molecular mechanism for DJ-1-dependent cancer cell invasion and metastasis.

Clinical Characteristics of Early-Onset Parkinson Disease in Mayo Clinic Population (P6-11.004)

<h3>Objective:</h3> To describe the demographic pattern and the clinical characteristics of the patients with Early Onset Parkinson’s Disease (EOPD) at the Mayo Clinic. <h3>Background:</h3> The causes of EOPD remain undefined; the clinical course and phenotypical characteristics of EOPD are different than those of late onset Parkinson disease. Unfortunately, there is still a gap of knowledge on EOPD. <h3>Design/Methods:</h3> We retrieved all the patients with EOPD that have visited the Mayo Clinic from 1990 to 2022 using Mayo Data Explorer (MDE). We included patients with a diagnosis of Parkinson’s disease (PD) at or before the age of 50 years old (according to the current Movement Disorder Society (MDS) recommendation on EOPD). In addition, we assessed the clinical features of those who were included. <h3>Results:</h3> A total of 838 (518 males and 320 females) patients with EOPD were included with a mean age at symptoms onset of 40.6 ± 6.7 years. Overall, 13.6% had a family history of PD, with only 4.5% with genetic testing. Resting tremor was reported in 84.8%, bradykinesia in 85.9%, rigidity in 81.3% and postural instability in 13.1%. Dyskinesias were documented in 44.4% with a mean time from PD diagnosis of 10.5 ± 6.2 years. Cognitive impairment was reported in 19.3% of patients with a mean time from PD diagnosis of 16.8 ± 14.3 years. <h3>Conclusions:</h3> We described the clinical characteristics of the EOPD in a large cohort. EOPD displays distinct clinical patterns regarding symptoms, progression, cognitive decline and response to medications. These differences may reflect multifactorial causes such as pathophysiological backgrounds and genetic, environmental, or age-related factors. <b>Disclosure:</b> Dr. Ghoniem has nothing to disclose. Dr. Jacobson has nothing to disclose. Aidan Mullan has nothing to disclose. Dr. Turcano has nothing to disclose. Dr. Camerucci has nothing to disclose. Mr. Stang has nothing to disclose. The institution of Dr. Bower has received research support from Abbvie. The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

Impulse Control Disorder and medication management in Patients with Early-Onset Parkinson’s Disease (P6-11.013)

<h3>Objective:</h3> To assess the usage frequency of dopamine agonists (DA), the prevalence of impulse control disorder (ICD) in patients with Early-onset Parkinson’s Disease (EOPD), and to explore the potential factors associated with the development of ICD. <h3>Background:</h3> Impulse control disorders are characterized by excessive and repetitive behaviors generally affecting patients exposed to DA. In previous studies, it has been reported that 1) there is an increased prevalence of ICD in patients with Parkinson’s disease and 2) ICD occurrence is associated with male sex and earlier disease onset. Patients with EOPD have an earlier disease onset and often face unique clinical and societal challenges. Given these factors and the scant current literature on ICD in EOPD, it is important to improve our understanding of ICD in this vulnerable population. <h3>Design/Methods:</h3> We used the Mayo Data Explorer system to investigate a population-based cohort of EOPD patients between 1990 and 2022 at Mayo Clinic. We included patients with Parkinson’s disease at or before the age of 50 (according to the current Movement Disorder Society recommendations) diagnosed with ICD. All medical records were reviewed to confirm diagnosis. <h3>Results:</h3> A total of 838 (518 males and 320 females) patients with EOPD were included with a mean age at symptom onset of 40.6 ± 6.7 years. DA was used in 47.4% of all patients. 24.2% of the patients using DA had ICD, and among these patients, 26% females and 23.1% males had ICD. There was no statistically significant difference in the frequency of ICD between males and females (p = 0.59). <h3>Conclusions:</h3> Our study demonstrates that DA was frequently used in patients with EOPD and that about 25% of these patients are affected by ICD. Our study also showed that there was no significant difference in the prevalence of ICD development between female and male patients. <b>Disclosure:</b> Dr. Jacobson has nothing to disclose. Dr. Ghoniem has nothing to disclose. Aidan Mullan has nothing to disclose. Dr. Turcano has nothing to disclose. Dr. Camerucci has nothing to disclose. Mr. Stang has nothing to disclose. The institution of Dr. Bower has received research support from Abbvie. The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.

Sleep Disturbances in Early Onset Parkinsonism (P7-11.010)

<h3>Objective:</h3> To compare the frequencies of sleep disorders between individuals with early onset parkinsonism (age ≤50 at motor symptom onset) and typical onset parkinsonism (age &gt;50 at motor symptom onset). <h3>Background:</h3> Sleep disturbances are common in parkinsonian disorders and have been well-studied in individuals with parkinsonism onset after age 50. Whether sleep disorders affect individuals with early onset parkinsonism and whether they differ from individuals with typical onset parkinsonism is unknown. <h3>Design/Methods:</h3> We used a population-based, 1991 to 2015 incident-cohort study of parkinsonism including 38 patients with early onset and 1001 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. Rates of sleep disorders before and after onset of parkinsonism were compared with logistic regression and Cox proportional hazards models. <h3>Results:</h3> Median (IQR) age of parkinsonism onset was 44.5 (41.0 – 48.7) years for early onset and 75.9 (67.7 – 81.7) years for typical onset patients. Parkinson’s disease (PD) was the most common cause of parkinsonism in each group. 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, with similar latencies of sleep disorders to parkinsonism diagnosis in each group. Early onset parkinsonism had a higher risk for developing insomnia compared with typical onset parkinsonism (HR 1.73, 95% CI: 1.02 – 2.93); the risk for developing all other sleep disorders was similar between groups. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Dr. McCarter has nothing to disclose. Dr. Camerucci has nothing to disclose. Aidan Mullan has nothing to disclose. Mr. Stang has nothing to disclose. Dr. Turcano has nothing to disclose. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. St. Louis has received publishing royalties from a publication relating to health care. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Dr. Bower has received research support from Abbvie. The institution of Dr. Savica has received research support from ACADIA Pharmaceuticals, Inc.