Young Parkinson's Disease Patients Research Articles

Age-Stratified Risk of Dementia in Parkinson's Disease: A Nationwide, Population-Based, Retrospective Cohort Study in Taiwan.

Introduction: Parkinson's disease (PD) manifests with dominant motor symptoms and a wide range of non-motor symptoms (NMS). Dementia is one of the most disabling and exhausting NMS throughout the clinical course. We conducted a population-based, age-stratified, retrospective cohort study to investigate the incidence rate and risk of dementia of patients with newly diagnosed PD, and linked to the clinicopathological PD subtypes.Methods: Patients with newly diagnosed PD (PD group, n = 760) and control subjects (non-PD group, n = 3,034) were selected from the Taiwan's National Health Insurance Research Database from January 2001 to December 2005. The dementia incidence rate and dementia-free survival rate were calculated.Results: The overall dementia incidence rate was 17.5 and 5.7 per 1,000 person-years in PD and non-PD groups, respectively. The PD group had a significantly higher overall risk of dementia than controls (p < 0.001). The younger PD patients had a lower dementia incidence rate than the older PD patients, but a higher dementia risk compared to the same age of controls (<60 years, adjusted HR 6.55, 95% CI 1.56–27.48, p = 0.010). The dementia-free survival rate was significantly lower in the PD group compared to the non-PD group during follow-up (p < 0.001).Conclusion: In our study, the older age of onset in PD patients resulted in a higher incidence rate of dementia. In the young age of PD patients, the incidence rate of dementia was lower than the older PD patients, but the dementia risk was higher than controls of the same age. These findings possibly implied that there were different pathogenesis and pathologies causing dementia in younger and older PD patients.

Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients

BackgroundImpaired bioenergetics are partially involved in the pathogenesis of Parkinson's disease (PD). Phosphoglycerate kinase (PGK), an essential enzyme for glycolysis, has recently attracted attention due to its pathogenic role in PD and as a target for disease-modifying therapies. This study is aimed to evaluate the profiles of PGK activity in red blood cells (RBCs) of PD patients and controls. MethodsSixty-eight PD patients and thirty-four age-matched unrelated controls were enrolled. PGK activities of RBCs were measured by the established colorimetric assay and standardized by the same RBC samples. ResultsPGK activity of the PD group was significantly higher than that of the control group in participants aged sixty-five years or younger, whereas it was not significantly different between the two groups at any age. PGK activity was positively correlated with aging in the control group, but this was not noted in the PD group. On multivariable analysis by partial correlation in the PD group, PGK activity was negatively correlated with the specific binding ratio of dopamine transporter scintigraphy in the striatum. The levodopa-equivalent daily dose was not significantly correlated with the enzyme activity. ConclusionThe results support the following: 1) elevation of PGK activities in RBCs can be detected in relatively young PD patients and with normal aging; 2) the degree of striatonigral degeneration is associated with elevated PGK activities. These are important considerations when the PGK assay is applied as a diagnostic biomarker of PD and to therapeutically monitor PGK-enhancing treatments.

Corrigendum: White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease.

[This corrects the article on p. 213 in vol. 9, PMID: 28713264.].

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease.

Background: White matter changes (WMC) are a common finding among older adults and patients with Parkinson's disease (PD), and have been associated with, e.g., gait deficits and executive dysfunction. How the factors age and PD influence WMC-related deficits is, to our best knowledge, not investigated to date. We hypothesized that advanced age and presence of PD leads to WMC-related symptoms while practicing tasks with a low complexity level, and low age and absence of PD leads to WMC-related symptoms while practicing tasks with a high complexity level.Methods: Hundred and thirty-eight participants [65 young persons without PD (50–69 years, yPn), 22 young PD patients (50–69 years, yPD), 36 old persons without PD (70–89 years, oPn) and 15 old PD patients (70–89 years, oPD)] were included. Presence and severity of WMC were determined with the modified Fazekas score. Velocity of walking under single and dual tasking conditions and the Trail Making Test (TMT) were used as gait and executive function parameters. Correlations between presence and severity of WMC, and gait and executive function parameters were tested in yPn, yPD, oPn, and oPD using Spearman's rank correlation, and significance between groups was evaluated with Fisher's z-transformed correlation coefficient.Results: yPn and yPD, as well as oPn and oPD did not differ regarding demographic and clinical parameters. Severity of WMC was not significantly different between groups. yPn and yPD displayed significant correlations of WMC with executive function parameters at low levels of task complexity, oPn at intermediate, and oPD at high complexity levels.Conclusion: This study argues for a relevant association of age and PD-related brain pathology with WMC-related gait and executive function deficits.

Comparable Neuroprotective Effects of Pergolide and Pramipexole on Ferrous Sulfate-Induced Dopaminergic Cell Death in Cell Culture.

Dopamine agonists are utilized clinically as an initial treatment in younger Parkinson's disease patients to delay the side effects associated with commencement of levodopa medication. These agonists also serveas adjunctive therapeutics with levodopa to lower the incidence of adverse motor symptoms in advanced stages of the disease. To compare the neuroprotective effects of the dopamine agonists pergolide and pramipexole on ferrous sulfate-induced neurotoxicity in dopaminergic neurons from primary mesencephalic cell culture. Pergolide (0.001-1 μM) and pramipexole (0.01-200 μM) were administered to 8 day primary murine mesencephalic cultures for 24 h. in the presence or absence of desferal, sulpiride or cycloheximide. Ferrous sulfate (450 μM) was then added for 24 hrs. Lactate dehydrogenase was assayed in the supernatant, glutathione concentrations measured in cell lysates and fixed cells were stained for tyrosine hydroxylase. Ferrous sulphate induced neurotoxity in cultures (p<0.0001) was abolished in the presence of the iron chelator desferal (p<0.008). Both pergolide (p<0.0001) and pramipexole (p<0.0001) significantly protected dopaminergic neurons against ferrous sulfate induced neurotoxicity and pramipexole helped preserve neurite morphology. Pramipexole treatment significantly reduced lactate dehydrogenase release (p<0.0001) as a measure of cellular injury. The dopamine receptor antagonist sulpiride (p<0.0001) and the protein synthesis inhibitor cycloheximide (p<0.0001) reduced the neuroprotective effects of pergolide indicating the involvement receptor stimulation and de novo protein synthesis in pergolide-mediated neuroprotection. Pramipexole also significantly reversed the decrease in cellular glutathione concentrations induced by ferrous sulfate (p<0.001). Both pergolide and pramipexole protect dopaminergic neurons against the neurotoxicity of ferrous sulfate. Pergolide specifically protects dopaminergic neurons through activation of dopamine receptors and de novo protein synthesis whereas pramipexole shows an overall effect through an antioxidant mechanism.

Reactive but not predictive locomotor adaptability is impaired in young Parkinson's disease patients

BackgroundGait and balance disorders are common in Parkinson's disease (PD) and major contributors to increased falling risk. Predictive and reactive adjustments can improve recovery performance after gait perturbations. However, these mechanisms have not been investigated in young-onset PD. ObjectiveWe aimed to investigate the effect of gait perturbations on dynamic stability control as well as predictive and reactive adaptability to repeated gait perturbations in young PD patients. MethodsFifteen healthy controls and twenty-five young patients (48±5yrs.) walked on a walkway. By means of a covered exchangeable element, the floor surface condition was altered to induce gait perturbations. The experimental protocol included a baseline on a hard surface, an unexpected trial on a soft surface and an adaptation phase with 5 soft trials to quantify the reactive adaptation. After the first and sixth soft trials, the surface was changed to hard, to examine after-effects and, thus, predictive motor control. Dynamic stability was assessed using the ‘extrapolated center of mass’ concept. ResultsPatients’ unperturbed walking was less stable than controls’ and this persisted in the perturbed trials. Both groups demonstrated after-effects directly after the first perturbation, showing similar predictive responses. However, PD patients did not improve their reactive behavior after repeated perturbations while controls showed clear locomotor adaptation. ConclusionsOur data suggest that more unstable gait patterns and a less effective reactive adaptation to perturbed walking may be a disease-related characteristic in young PD patients. These deficits were related to reduced ability to increase the base of support.

LRRK2 A419V variant is a risk factor for Parkinson's disease in Asian population

Recently, LRRK2 A419V (rs34594498) was reported associating with Parkinson's disease (PD) in Asian population; yet the conclusion is still unobvious. We conducted a case-control study to determine the potential associations between A419V and PD in Chinese population. Five hundred PD patients and 574 health controls were genotyped. Our results showed, A419V has a significantly higher frequency among PD patients than the controls (p = 0.025, odds ratio [OR] = 2.57, 95% confidence interval [CI] [1.13–5.86]), especially in early-onset PD (p = 0.027, OR = 10.40, 95% CI [1.31–82.89]). And PD patients who carried A419V have a lower Minimum-Mental State Examination scores than PD patients who did not (p = 0.04). We also conducted a meta-analysis on A419V. In Asian population, A419V was detected at a significantly higher frequency among PD patients in contrast to controls: Z = 2.47, p = 0.01, OR = 2.11, 95% CI [1.17–3.82]. When only considering the Chinese population, the difference was more obvious with Z = 3.41, p = 0.0007, OR = 2.07, 95% CI [1.36–3.14]. The results suggest LRRK2 A419V appears to be a risk factor for PD in Asian, especially in early-onset patients. Finally, larger sample with centering on young or cognitive impairment PD patients in Asian would be preferable for further confirmation.

Korábban és hatékonyabban: a mély agyi stimuláció szerepe a munkaképesség megôrzésében

The recently published "EarlyStim" study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. We reviewed the data of 39 young (< 60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job ("Job+" group, n = 15) and retired patients (without active job, "Job-" group, n = 24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p < 0.01, McNemar test). Although our retrospective study has several limitations, our results fit well with the conclusions of "EarlyStim" study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.

Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension, stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease

BackgroundEspecially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD. MethodsBased on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated. ResultsPD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02).After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD. ConclusionClear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.

Parkinson’s disease: how is employment affected?

Rates of unemployment and early retirement are increased in Parkinson's disease (PD) and contribute to disease burden. To investigate time to loss of employment from PD onset and predictors of continued employment; to identify common issues and possible interventions in the workplace. Eighty-eight patients with PD diagnosed at age≤65 years took part in a retrospective cohort study. Veterans RAND Short Form-36 and an employment survey were administered. Unemployment rates for males were increased compared to the general Irish population (standardized ratio of 1.6, 95% CI 1.2-2.2, P<0.05). There was no significant difference for females. Median retirement age was 58 years for males and 61 years for females compared to 63.5 and 65 years, respectively, in the general population. In survival analysis, median time to loss of employment was 7 years (95% CI 4.8-9.2). After 5 years, 40% remained working and 14% after 10 years. Early age of PD onset (P<0.001), early diagnosis (P<0.002) and high scores in vitality (P<0.005) were associated with prolonged employment. There was no association with sex, education, type or hours of work. Slowness, fatigue and tremor were the most challenging symptoms at work. Changes in work schedule and type of work were suggested helpful adjustments. Loss of employment places a significant socioeconomic burden on young PD patients. More detailed examination of specific issues and reasonable adjustments is needed, along with patient and employer education.

Dopaminergic function and progression of Parkinson's disease: PET findings

Recent PET studies in Parkinson's disease (PD) have shown that the progression of neurodegeneration follows an exponential decay pattern. Most of the damage to the nigrostriatal dopamine system occurs during the presymptomatic phase of the disease and the first few years following symptom onset. The progressive loss of dopaminergic neurons is accompanied by several functional adaptive changes in surviving nerve terminals, which lead to increased dopamine turnover and raise the risk of treatment-related motor complications. Younger PD patients seem to have more efficient compensatory mechanisms and a slower rate of progression of neurodegeneration.

Altered Regulation of CD200 Receptor in Monocyte-Derived Macrophages from Individuals with Parkinson’s Disease

Microglia are the representative myeloid cells in the brain, and their over-activation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia activation is believed to be regulated by the CD200-CD200R signaling. As the peripheral counterpart of microglia, monocyte-derived macrophages (MDMs) share the same progenitor and antigen markers, and they have similar biological behaviors and mirror microglial function in the brain. Here, we studied CD200R expression and its regulation in MDMs from 32 PD cases, 27 age-matched old controls, and 28 young controls. We found that the basal CD200R expression is similar in MDMs from young control, old control and PD patients. However, the induction of CD200R expression in MDMs under various conditions is impaired in the old groups, especially in PD patients. There was a selective decrease in CD200R expression induced by co-culture with dying PC12 cells in MDMs from PD cases, as compared with MDMs from the age-matched controls. We also found that the inducible CD200R expression correlated inversely with the onset age of PD and to tumor necrosis factor-alpha (TNF-alpha) released from MDMs. These results suggest an intrinsic abnormality in the CD200-CD200R signaling in MDMs during aging and, especially, in PD. We speculate that in the PD brain,microglia might undergo abnormalities similar to MDMs.

A study of cognitive functions in young Parkinsonian patients.

The purpose of the study was to evaluate the neuropsychological performance of younger Parkinson's disease (PD) patients compared to healthy controls. A group of young optimally treated PD patients younger than 56 years was pair-matched with a group of healthy controls for age, social class and the two WAIS subtests "vocabulary" and "similarities". As a group, the PD patients were satisfactory in verbal logical intelligence, but evaluation of neuropsychological tests showed difficulties in short memory span, constructional function and logical visual sequential cognition. Young PD patients have some cognitive impairment for which they are able to compensate for a time because of preserved intelligence. More attention should be paid to possible problems in their jobs and social life.

Young Women with PD

ABSTRACT Parkinson's Disease (PD) prior to the age of 40 affects between 5-10% of the PD population. The psychosocial changes that patients with early PD encounter, may be more devastating and disabling than the actual motor disability. The paper describes a unique experience in groupwork with young female PD patients treated in the Movement Disorders Unit of the Tel Aviv Sourasky Medical Center. The paper focuses on the special issues which characterized this group's experience: stigma, body and sexual image, and personality traits.

Personality traits in young patients with Parkinson's disease.

It has been hypothesized that the dopaminergic deficit of older patients with Parkinson's disease (PD) is associated with a reduction in the dopamine-dependent personality trait "novelty seeking". It is unknown whether this may also be found in younger patients with PD whose dopaminergic deficit is considered to be purely motor. We interviewed 122 patients below 51 years of age and 122 age- and sex-matched healthy controls with regard to clinical and sociodemographic data. Both groups had to fill out the Tridimensional Personality Questionnaire (TPQ) of Cloninger. Neuropsychological testing of formal intelligence and depression was also applied. "Novelty seeking" was not different between both groups. Patients were more often depressed than controls, explaining their difference in "harm avoidance" on the TPQ. "Persistence", a sub-scale of the third TPQ dimension "reward dependence", was significantly higher in patients. Neither sex, nor age, nor educational status were correlated with one of the three personality traits. The higher rate of depression explains our finding of more "harm avoidance" among young PD patients. According to a literature review the choice and performance of controls is crucial whether personality traits in PD patients may be assessed as abnormal.

Prognosis of Parkinson's disease in Japan. Tottori University Parkinson's Disease Epidemiology (TUPDE) Study Group.

Therapy for Parkinson's disease (PD) has been progressing. However, the prognosis for patients with PD is still unclear. We studied the course of PD in patients in the San-in Area of Japan over a long time period. The main purpose of this study was to see whether there was a difference in survival between PD patients and the general population. Information on 114 deceased PD patients, who died between 1989 and 1996, was collected from hospitals belonging to the Tottori University Parkinson's Disease Epidemiology Study Group. Although the duration of illness was prolonged, the survival of PD patients was still poorer than that of the general population. The most common cause of death was pneumonia. The main cause of death in young PD patients was also pneumonia. In order to improve the survival of PD patients, PD-related conditions should be treated more extensively, especially pneumonia.

Risk of dementia in patients with Parkinson's disease, epilepsy, and severe head trauma: a register-based follow-up study.

The authors investigated the risk of developing dementia for persons aged 50-75 years who suffered from Parkinson's disease, epilepsy, or severe head trauma. They compared the risk in this patient group with the risk in a reference group in a follow-up study based on the linked databases of three Dutch nationwide morbidity registers over the years 1980-1989. The overall relative risk of developing dementia within 8 years in patients with Parkinson's disease who were initially free of dementia was 3.0 (95% confidence interval (CI) 2.9-3.1). Risk was especially increased in younger Parkinson's disease patients (relative risk (RR) = 13.2, 95% CI 6.2-28.6). For patients with epilepsy, the overall relative risk was 1.5 (95% CI 1.4-1.7). Severe head trauma was not associated with an increased risk of dementia (RR = 1.0, 95% CI 0.9-1.1). These findings suggest that Parkinson's disease is an important risk factor for dementia, with a particularly high risk in young patients with Parkinson's disease. Patients with epilepsy may bear a moderately increased risk of developing dementia. This study does not support earlier findings in retrospective case-control studies of an increased risk of dementia in head trauma patients.