Late-onset Parkinson's Disease Patients Research Articles

Reproductive life factors and estro-progestin exposure in women with early-onset Parkinson's disease compared to late-onset disease and controls: A retrospective cohort study

BackgroundParkinson's disease (PD) is more common in men than women. Although hormonal factors may partially explain this difference, there are no studies evaluating reproductive life factors and exogenous estroprogestin exposure in women with Early Onset Parkinson Disease (EOPD). ObjectiveTo compare reproductive life factors and exogenous estroprogestin exposure among female patients with EOPD, late-onset Parkinson's disease (LOPD), and EOPD-matched unaffected controls. MethodsWe identified female patients with EOPD from 1989 to 2021, defining EOPD as PD with motor-symptoms onset before age 50 and LOPD as PD with motor onset after 50. We paired EOPD patients to age-matched, unaffected controls. We reviewed medical records to determine demographic characteristics, clinical history, and reported reproductive menopausal history (reviewing medical records). ResultsWe included 87 EOPD patients, 84 LOPD patients, and 91 unaffected controls with information about reproductive life factors and exogenous estroprogestin exposure in their medical records. There were no significant differences in race, ethnicity, or BMI between the three groups. EOPD patients were more likely to have used hormonal contraception than LOPD patients (23/49 (47 %) vs 0/84 (0 %), p < 0.001). LOPD patients had higher numbers of pelvic surgeries (48/84 [57 %] in LOPD, 23/87 [26 %] in EOPD, p < 0.001) and higher usage of perimenopausal hormonal therapy (52/84 [62 %] in LOPD, 10/87 [11 %] in EOPD, p < 0.001) in LOPD than EOPD. ConclusionsOur study reports no significant difference in reproductive life factors and exogenous estroprogestin exposure between controls and EOPD patients, except for higher exposure to hormonal contraception in EOPD. There was no apparent difference in reproductive life factors and exogenous estroprogestin exposure between EOPD and LOPD patients. Our findings therefore do not observe that hormonal exposure is different between earlier onset of female EOPD compared to female LOPD patients, or between female EOPD patients and unaffected female controls.

Comparison of disability level between Early and Late Onset Parkinson's Disease using WHODAS 2.

Parkinson's disease (PD) is a degenerative neurological disorder that usually affects people over the age of 60. However, 10%-20% of patients have an early onset of PD (EOPD). To compare disability levels according to the World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2) between people with EOPD and those with late-onset PD (LOPD). We conducted a cross-sectional study with 95 EOPD patients (mean-age 44.51 ± 4.63, H&Y 1.93 ± 0.93) and 255 LOPD patients (mean-age 63.01 ± 7.99, H&Y 2.02 ± 0.95). Demographic information, clinical characteristics, cognitive evaluation by Telephone-Montreal-Cognitive-Assessment (T-MoCA), functionality self-evaluation by WHODAS-2 and the Unified-Parkinson's-Disease-Rating-Scale (MDS-UPDRS), parts I and II, were documented for each patient by an individual remote interview. Analysis showed a statistically significant difference between EOPD and LOPD in two domains of WHODAS-2 only: cognition (Z-adjusted = 2.60; p-value adjusted <0.009) and activities of daily living related to work/school (Z-adjusted = 2.34; p-value adjusted <0.01). T-MoCA scores confirmed more impaired cognition capacity in LOPD (Z-adjusted = 2.42; p-value adjusted <0.01). The two groups had no significant differences in levodopa daily dosage, Hoehn and Yahr (H&Y) stages, disease time duration, and MDS-UPDRS I and II scores. People living with EOPD face similar disability levels as those with LOPD, except for cognition, where LOPD patients exhibited higher levels of disability than EOPD and for work activities where the EOPD exhibited higher levels of disability than LODP. These results highlight the challenges faced by people with EOPD in interacting with society and living with the disease for a longer time. The WHODAS-2 can be a useful tool to assess disability and tailor interventions for people with PD of different age groups.

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.

Effects of soluble TREM2 on motor progression in Parkinson’s disease

ObjectivesTo determine whether sTREM2 is changed during the pathogenesis of PD and reflect motor decline in PD individuals. MethodsThe cerebrospinal fluid (CSF) from PD and healthy individuals were obtained to measure the expression of sTREM2 and further to evaluate the motor function at baseline and after four years of follow-up using the Parkinson’s Progression Markers Initiative (PPMI) database. The relationship between motor disease progression at baseline and longitudinal CSF sTREM2 was evaluated by linear mixed-effects (LME) and multiple linear regression (MLR) models. The change rates of the motor symptoms and sTREM2 level in CSF were further rigorously analyzed using the LME model. Cox proportional-hazards regression models were used to evaluate the predictive values of sTREM2 in CSF for motor progression. The regulatory role of CSF α-syn and Tau between sTREM2 and motor assessments was evaluated by Mediating effect analysis. ResultsWe found no significant difference in CSF sTREM2 levels between the PD and HC groups (p = 0.155). However, late-onset PD patients had higher CSF sTREM2 levels than early-onset PD patients (p = 0.044). The basal levels of sTREM2 could predict motor progression over the four years of follow-up. The change rate of CSF sTREM2 was correlated with the progressive deterioration of motor function in PD individuals. Our observations also showed that CSF Tau was a significant mediator of the association between CSF sTREM2 and total UPDRS scores and UPDRS III and tremor at baseline with 26.5% and 33.5%, and 28.7% mediation, respectively. ConclusionOur results indicated that CSF sTREM2 was associated with the prognosis of PD motor symptoms. Besides, CSF Tau could effectively mediate the association of sTREM2 with motor progression.

Free-Water Imaging of the Substantia Nigra in GBA Pathogenic Variant Carriers.

Pathogenic variants in the glucocerebrosidase gene (GBA) have been identified as the most common genetic risk factor for Parkinson's disease (PD). However, the features of substantia nigra damage in GBA pathogenic variant carriers remain unclear. We aimed to evaluate the microstructural changes in the substantia nigra in non-manifesting GBA pathogenic variant carriers (GBA-NMC) and PD patients with GBA pathogenic variant (GBA-PD) with free-water imaging. First, we compared free water values in the posterior substantia nigra between non-manifesting non-carriers (NMNC, n=29), GBA-NMC (n=26), and GBA-PD (n=16). Then, free water values in the posterior substantia nigra were compared between GBA-PD and early- (n=19) and late-onset (n=40) idiopathic PD (iPD) patients. Furthermore, we examined whether the baseline free water values could predict the progressions of clinical symptoms. The free water values in the posterior substantia nigra were significantly higher in the GBA-NMC and GBA-PD groups compared to NMNC, and were significantly increased in the GBA-PD group than both early- and late-onset iPD. Free water values in the posterior substantia nigra could predict the progression of anxiety and cognitive decline in GBA-NMC and GBA-PD groups. We demonstrate that free water values are elevated in the substantia nigra and predict the development of non-motor symptoms in GBA-NMC and GBA-PD. Our findings demonstrate that a significant nigral impairment already exists in GBA-NMC, and nigral injury may be more severe in GBA-PD than in iPD. These results support that free-water imaging can as a potential early marker of substantia nigra damage. © 2023 International Parkinson and Movement Disorder Society.

Evaluating the Genetic Role of Circadian Clock Genes in Parkinson's Disease.

Increasing evidence suggests that circadian dysfunction is related to Parkinson's disease (PD). However, the role of circadian clock genes in PD is still poorly understood. This study aimed to illustrate the association between genetic variants of circadian clock genes and PD in a large Chinese population cohort. Ten circadian clock genes were included in this study. Whole-exome sequencing (WES) was conducted in 1997 early-onset or familial PD patients and 1652 controls (WES cohort), and whole-genome sequencing (WGS) was conducted in 1962 sporadic late-onset PD patients and 1279 controls (WGS cohort). Analyses were completed using the optimized sequence kernel association test and regression analyses. In the burden analysis of the circadian clock gene set, we found suggestive significant associations between the circadian clock genes and PD in the WES cohort when considering missense, damaging missense (Dmis), and deleterious variants. Moreover, the burden analysis of single genes revealed suggestive significant associations between PD and the loss-of-function variants of the CRY1 gene, missense, Dmis, and deleterious variants of the PER1 gene, and Dmis and deleterious variants of the PER2 gene in the WES cohort.Rare variants in the WGS cohort and all common variants in the WGS and WES cohorts were unrelated to PD. Phenotypic analysis indicated that deleterious variants of the PER1 gene were associated with dyskinesia in the WES cohort. Our study provides evidence of a potential link between circadian clock genes and PD from a genetic perspective.

Association of HMOX-1 rs2071747 with sporadic Parkinson's disease in southern Han Chinese.

To discover the associations between HMOX-1 and sporadic Parkinson's disease (PD). Five hundred sporadic PD patients and 500 healthy controls were recruited in this study. Polymerase chain reaction (PCR) was used. The dominant model of HMOX-1 rs2071747 was shown statistically significant between PD patients and control after adjustment of age and gender (dominant model: p value: 0.045, OR: 1.51, 95% CI: 1.01-2.27, adjusted). The associations of additive model and dominant model of rs2071747 were also found (additive model: p value: 0.047; dominant model: p value: 0.035, OR: 1.55, 95% CI: 1.03, 2.34). We found the association of the dominant of HMOX1 rs2071747 with PD. We also found the associations of additive model and dominant model of HMOX1 rs2071747 with late onset PD (LOPD) patients. • The dominant model of HMOX1 rs2071747 was associated with PD. • The additive model of HMOX1 rs2071747 was associated with LOPD. • The dominant model of HMOX1 rs2071747 was associated with LOPD.

Evaluating the role of ARSA in Chinese patients with Parkinson's disease

Recent studies have suggested ARSA, a gene responsible for metachromatic leukodystrophy, could be a genetic modifier of Parkinson's disease (PD) pathogenesis, acting as a molecular chaperone for α-synuclein. To elucidate the role of ARSA variants in PD, we did a comprehensive analysis of ARSA variants by performing next-generation sequencing on 477 PD families, 1440 sporadic early-onset PD patients and 1962 sporadic late-onset PD patients and 2636 controls from Chinese mainland, as well as the association between ARSA variants and cognitive function of PD patients. We identified 2 familial PD following autosomal dominant inherence carrying rare variants of ARSA, but they had limited clinical significance. We detected a total of 81 coding variants of ARSA in our subjects but none of the identified variants were associated with either susceptibility or cognitive performance of PD, while loss-of-function variants showed slightly increased burden in late-onset PD (0.25% vs. 0%, p = 0.08). Our results suggested ARSA may not play important roles in PD of Chinese population.

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson\u2019s disease

BackgroundThe clinical characteristics of Parkinson’s disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression.ObjectiveTo explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO).MethodsDemographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality.ResultsSleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep.ConclusionMore attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

GAA gene variants and genotype-phenotype correlations in patients with glycogen storage disease type Ⅱ

Objectives: To explore the GAA varient spectrum and the genotype-phenotype correlations in patients with glycogen storage disease type Ⅱ (Pompe disease, PD), as well as to estimate the disease incidence based on carrier rate of GAA varients in Guangzhou population. Methods: A total of 57 PD cases were retrospectively enrolled at Guangzhou Women and Children's Medical Center from January 1, 2010 to May 31, 2020. All patients presented symptoms before the age of 18 years. Each diagnosis was further confirmed by GAA enzyme activity and GAA variants. The carrier rate of GAA varients was calculated based on variants detected by whole exon sequencing among 2 395 healthy children in Guangzhou. Results: Among the 57 PD patients (including male 26, female 31),twenty-eight patients with infantile onset PD (IOPD) presented with progressive general muscle weakness and cardiomyopathy. The mean ages of symptom onset and diagnosis were (2.5±1.4) and (5.0±3.0) months, respectively. Twenty-six cases died in the first year after birth.Twenty-three patients with late onset PD (LOPD) presented with progressive muscle weakness. Seven of them had respiratory failure at diagnosis. The mean ages of symptom onset and diagnosis were (12.0±5.0) and (17.0±7.5) years, respectively. Six children with atypical IOPD showed motor delay, muscle weakness and cardiomyopathy. Their diagnosis was confirmed at 2.5-7.0 years of age. Among the 57 patients, 47 different variants were identified in the GAA gene. Three variants: c.797C>T, c.1109G>A and c.1757C>T were novel. c.1935C>A (25/114, 21.9%) and c.2238G>C (15/114, 13.2%) were the most common variants, detected in 57.1% of IOPD and 65.2% (15/23) of LOPD patients, respectively. Among the 28 IOPD patients, 26 cases (92.9%) carried at least one missense variant which indicated positive cross-reactive immunologic material (CRIM). The carrier rate of pathogenic variants in GAA gene among healthy children was 24/2 395. The estimated incidence of PD in this population is about 1/40 000. The frequencies of pseudodeficiency variants c.1726G>A and c.2065G>A homozygotes were 26.3% (15/57) and 35.1% (20/57) in PD patients, which were significantly higher than those (1.7% (40/2 395) and 3.9% (94/2 395)) in healthy children (χ²=151.2, 121.9; both P<0.01). Conclusions: PD presents as a spectrum, some as atypical IOPD. The c.1935C>A and c.2238G>C are common variants, correlated with IOPD and LOPD respectively. The c.796C>T and c.1082C>T are usually found in atypical IOPD. The majority of IOPD patients is predicted to be CRIM positive. The estimated incidence of PD is about 1/40 000.

Clinical manifestations of Parkinson's disease harboring VPS35 retromer complex component p.D620N with long-term follow-up

IntroductionTo identify and investigate patients with Parkinson's disease (PD) harboring VPS35 variants in Japan. MethodsUsing targeted gene panel screening, we analyzed 393 familial, 294 young-onset, and 52 late-onset sporadic PD patients derived from the Juntendo PD DNA bank, and obtained clinical information from the medical records on each patient in whom we found VPS35 p.D620N variants. ResultsWe identified VPS35 p.D620N in three new patients: two patients with familial PD and one patient with sporadic PD. Additionally, we newly confirmed p.D620 from a patient of a family reported previously. The prevalence of familial PD was 0.7% (2/307), young-onset sporadic PD was 0.3% (1/294), and late-onset sporadic PD was 0% (0/52) in our cohort. Combining four patients with p.D620N from our previous reports, haplotype analysis indicated at least two founders in our cohort. Patients commonly showed a slow progression of parkinsonism with onset in middle or late age and mild parkinsonism with good response to levodopa and little cognitive decline even for more than 10 years of disease duration. Psychosis was occurred in two patients. One-half of patients required device-aided therapies such as deep brain stimulation or levodopa-carbidopa intestinal gel. Brain magnetic resonance imaging mostly showed normal findings, even at more than 10 years after onset. 123I-metaiodobenzylguanidine myocardial scintigraphy indicated normal heart-to-mediastinum ratio values among three of four patients. Conclusions: Patients with VPS35 p.D620N showed distinctive symptoms and neuroimaging. Our findings expand the clinical findings of patients with VPS35 variants.

Contribution of coding/non-coding variants in NUS1 to late-onset sporadic Parkinson's disease

IntroductionA recent study reported that rare variants in NUS1 were associated with Parkinson's disease (PD). We aimed to assess the relative contribution of rare and common coding/non-coding variants of NUS1 to late-onset PD patients (LOPD). MethodsWhole genome sequencing data were analyzed for target NUS1 regions, derived from a cohort of 1962 cases and 1279 controls. The genetic association analyses were performed using logistic regression analysis and Sequence Kernel association test. Expression quantitative trait loci (eQTL) analysis was conducted to further explore the association of variants with NUS1 expression based on the data from GTEx database. ResultsWe identified 18 rare coding variants. p.Y131C was first identified in LOPD. However, no significant burden of rare NUS1 coding variants in LOPD was found. The rare variant sets of two regulatory elements (GH06J117605 and GH06J117674) were significantly enriched in LOPD even after Bonferroni correction (adjusted P = 0.013; adjusted P = 0.010). Considering the joint effect of rare and common variants, all variant sets within GH06J117605 and GH06J117674 showed association with LOPD but were no longer significant after Bonferroni correction. None of the common variants within coding/non-coding regions were significant after Bonferroni correction. The eQTL results suggested these variants in GH06J117605 and GH06J117674 could potentially have eQTL effects on the brain tissues. ConclusionsThese findings provide novel insight into the role of NUS1 regulatory regions in the development of LOPD and indicate that the variants in regulatory elements of NUS1 may be associated with LOPD by influencing the gene expression level.

Suicidal ideation in early-onset Parkinson’s disease

Patients with early-onset Parkinson's disease (EOPD) often suffer from more frequent depression than those with late-onset Parkinson's disease (LOPD). However, the clinical characteristics of suicidal ideation (SI) in EOPD remains unknown. This study aimed to explore the prevalence, related factors, and predictive factors of SI in EOPD patients as well as comparison of the prevalence in LOPD patients. We conducted a case-control, cross-sectional, and longitudinal study. Propensity score matching (PSM) was used to balance the characteristics between EOPD (N = 577) and LOPD patients (N = 2973). The diagnosis of SI was based on the assessment of the Beck Depression Inventory (BDI). EOPD patients with a disease duration < 5years (N = 96) were prospectively followed-up for exploring the predictors for the development of SI. Two forward binary logistic regression models were respectively used to explore the associated and predictive factors of SI. After PSM, EOPD patients showed significantly higher prevalence of SI than LOPD patients (22.0 vs. 13.3%, P < 0.001). Twenty EOPD patients (20.8%) developed SI and none of them reported suicidal behaviors after a median of 2.7 (IQR = 1.6-4.1) years. Depression, dyskinesia, non-smoking, lower education, and higher Non-Motor Symptoms Scale (NMSS) score were independently associated with the presence of SI. Depression at baseline was the only independent risk factor for the future occurrence of SI. Our study highlights the necessity to screen SI in patients with EOPD especially for those with depression.

Screening non-MAPT genes of the Chr17q21 H1 haplotype in Parkinson's disease

IntroductionThe microtubule-associated protein tau (MAPT) gene is considered a strong genetic risk factor for Parkinson's disease (PD) in Caucasians. MAPT is located within an inversion region of high linkage disequilibrium designated as H1 and H2 haplotype, and contains eight other genes which have been implicated in neurodegeneration. The aim of the current study was to identify common coding variants in strong linkage disequilibrium (LD) within the associated loci on chr17q21 harboring MAPT. MethodsSanger sequencing of coding exons in 90 Caucasian late-onset PD (LOPD) patients was performed. Specific gene sequencing for LRRC37A, LRRC37A2, ARL17A and ARL17B was not possible given the high homology, presence of pseudogenes and copy number variants that are in the region, and therefore four genes (NSF, KANSL1, SPPL2C, and CRHR1) were included in the analysis. Coding variants from these four genes that did not perfectly tag (r2 = 1) the MAPT H1/H2 haplotype were genotyped in an independent replication series of Caucasian PD cases (N = 851) and controls (N = 730). ResultsIn the 90 LOPD cases we identified 30 coding variants. Eleven non-synonymous variants tagged the MAPT H1/H2 haplotype, including two SPPL2C variants (rs12185233 and rs12373123) that had high pathogenic combined annotation dependent depletion (CADD) scores of >20. In the replication series, the non-synonymous KANSL1 rs17585974 variant was in very strong LD with MAPT H1/H2 and had a high CADD score of 24.7. ConclusionWe have identified several non-synonymous variants across neighboring genes of MAPT that may warrant further genetic and functional investigation within the biological etiology of PD.

Age-dependent efficacy of subthalamic nucleus deep brain stimulation in young- and late-onset Parkinson's disease based on a 10 year follow-up

IntroductionLong-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS. MethodsStatistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores. ResultsTen years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16–22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects. ConclusionTen years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.

DaTSCAN (123I-FP-CIT SPECT) imaging in early versus mid and late onset Parkinson's disease: Longitudinal data from the PPMI study

IntroductionIt has been reported that early onset Parkinson's Disease (PD) patients have a less profound dopaminergic degeneration. The aim of the current study was to determine whether there are longitudinal differences in dopaminergic denervation [signal reduction in 123I-FP-CIT SPECT] in early versus mid and late onset PD. MethodsDaTSCAN (123I-FP-CIT SPECT) imaging was acquired at Parkinson's Progression Markers Initiative (PPMI) imaging centers and sent to the imaging core for calculation of striatal binding ratios. Data from the PPMI database of 58 early de novo PD patients (age ≤ 50 years) were compared to those of 362 mid and late onset PD patients (age > 50 years). ResultsAlthough raw striatal binding ratios were higher in early onset versus mid/late onset PD, especially on the ipsilateral side, such differences were not observed, and were in fact reversed in the contralateral putamen, after age correction. The rate of signal decline was similar between the two groups. Interestingly, based on both raw and age-adjusted data, caudate nucleus and putamen asymmetry (contralateral/ipsilateral ratio) was more pronounced in early onset PD. Striatal asymmetry also significantly correlated with age at onset as a continuous variable. ConclusionEarly onset PD patients exhibited similar rates of decline of dopaminergic denervation compared to mid/late onset PD. These results are not supportive of a more benign disease in this subgroup. The more pronounced asymmetry in early onset PD may however signify a qualitatively different pattern of neurodegeneration compared to mid/late onset PD.

Dopamine Transporter, Age, and Motor Complications in Parkinson's Disease: A Clinical and Single-Photon Emission Computed Tomography Study.

Previous molecular imaging studies comparing dopamine function in vivo between early-onset PD and late-onset PD patients have shown contradictory results, presumably attributable to the aging-related decline in nigrostriatal function. (1) To investigate baseline dopamine transporter availability in early-onset PD (<55 years) and late-onset PD (>70 years) patients, z-scores values of putamen and caudate [123 I]-ioflupane uptake were calculated using the respective age-matched controls in order to correct for early presynaptic compensatory mechanisms and age-related dopamine neuron loss; (2) to examine the associations of such baseline single-photon emission computed tomography measures with the emergence of late-disease motor complications. In this retrospective study, 105 de novo PD patients who underwent [123 I]-ioflupane single-photon emission computed tomography at time of diagnosis were divided into three tertile groups according to age at disease onset (35 early-onset PD and 40 late-onset PD patients). Z-scores were compared between the two groups, and their predictive power for motor complications (during a mean follow-up of 7 years) was evaluated using Cox proportional hazard models. Despite a less-severe motor phenotype, early-onset PD patients exhibited more reduced [123 I]-ioflupane binding in the putamen and had a higher and earlier risk for developing motor complications than those with late-onset PD. Lower [123 I]-Ioflupane uptake in the putamen and caudate increased the risk of motor complications. Our findings indicate that a lower dopamine transporter binding in early-onset PD predicts the later development of motor complications, but it is not related to severity of motor symptoms, suggesting age-related differences in striatal compensatory mechanisms in PD. © 2020 International Parkinson and Movement Disorder Society.

ALFF and ReHo Mapping Reveals Different Functional Patterns in Early- and Late-Onset Parkinson's Disease.

Heterogeneity between late-onset Parkinson’s disease (LOPD) and early-onset Parkinson’s disease (EOPD) is mainly reflected in the following aspects including genetics, disease progression, drug response, clinical manifestation, and neuropathological change. Although many studies have investigated these differences in relation to clinical significance, the functional processing circuits and underlying neural mechanisms have not been entirely understood. In this study, regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) maps were used to explore different spontaneous brain activity patterns in EOPD and LOPD patients. Abnormal synchronizations were found in the motor and emotional circuits of the EOPD group, as well as in the motor, emotional, and visual circuits of the LOPD group. EOPD patients showed functional activity change in the visual, emotional and motor circuits, and LOPD patients only showed increased functional activity in the emotional circuits. In summary, the desynchronization process in the LOPD group was relatively strengthened, and the brain areas with changed functional activity in the EOPD group were relatively widespread. The results might point out different impairments in the synchronization and functional activity for EOPD and LOPD patients.

Generation of 5 hiPSC lines derived from three unrelated idiopathic Parkinson disease patients and two unrelated healthy control individuals.

We describe generation of human induced pluripotent stem cell (hiPSC) lines of three unrelated idiopathic late onset Parkinson disease patients and two healthy controls above 60 years of age without neurological diseases nor Ashkenazi ancestry. Human iPSC were derived from peripheral blood-erythroblasts using integration free episomal plasmids carrying four reprogramming factors OCT4, SOX2, c-MYC, KLF4 and BCL-XL. The hiPSC lines were characterized according to established criteria.

Executive dysfunctions and behavioral changes in early drug-naïve patients with Parkinson's disease

ObjectivesThis study aims to explore the clinical profiles and onset age-related difference of executive dysfunctions and behavioral changes in early drug-naïve patients with Parkinson's disease (PD). MethodsA cross-sectional analysis on 419 early stage drug-naïve PD patients was conducted. The frontal assessment battery (FAB) was used to assess executive functions and the frontal behavioral inventory (FBI) was used to assess behavioral changes. ResultsExecutive dysfunctions were detected in 113 patients (27.0%), and 219 patients (52.3%) displayed varied degrees of behavioral changes. The most frequent affected domain for the FAB was lexical fluency (31.7%), while the three most frequent affected domains for the FBI were apathy (26.0%), irritability (24.3%) and inattention (20.8%). Compared to the early-onset PD (EOPD) patients, the late-onset PD (LOPD) patients exhibited significantly higher frequent damage in FAB especially similarities, motor series, and conflicting instructions as well as lower frequent damage in lexical fluency. The frequencies of FBI-abnormal were not different between the two groups. Multivariate analyses indicated that age at PD onset was independently associated with FAB total score and its subscores including lexical fluency, motor series, conflicting instructions and go-no go task, but it has no relationship with FBI total score and its subscores. ConclusionsExecutive deficits and behavioral changes are common in the early stage of PD. Age at PD onset is independently associated with the performance of executive functions. However, behavioral changes in PD may be not affected by onset age.