Introduction
To test drugs with the potential to prevent the onset of Parkinson’s disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is ...often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems).
Objective
We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls.
Methods
We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6.
Results
Constipation had an adjusted odds ratio, 6.14 95% CI: 2.94–12.80 showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 95% CI: 7.88–48.81 showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively.
Discussion
Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.
Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor ...features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration.
Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression.
The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score.
Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigates longitudinal changes in self-reported physical activity, measured by Physical Activity Scale of the Elderly (PASE), in early Parkinson's disease (PD) and matched healthy ...control (HC) participants in the Parkinson's Progression Marker Initiative (PPMI) and evaluates associations between physical activity and PD progression.
PPMI is a prospective, longitudinal study evaluating markers of progression in PD participants who are unmedicated at enrollment. PASE, a self-reported measure of physical activity, was administered to early PD (N = 380) and HC (N = 174). PASE was introduced after study launch and therefore administered at years 2, 3, and 4. PASE scores for PD and HC were compared with t-tests and changes over time were evaluated with generalized estimating equations.
There were no differences in activity levels between PD and HC at any time point. However, PD participants had a longitudinal decrease in PASE from years two to four (p = 0.034), while HC did not (p = 0.89). In exploratory analyses controlling for age, sex, and disease duration, higher self-reported activity at year 2 were associated with slower progression of motor symptoms (p = 0.018), ADL performance (p < 0.0001), depression (p = 0.001), anxiety (p = 0.002), and cognitive decline (p = 0.016) over two years. These findings remained significant after adjusting for disease severity.
There are no differences in self-reported physical activity between HC and early PD, but activity levels decline longitudinally in PD. Exploratory analyses show that higher self-reported physical activity is associated with less disease progression. Therefore, interventions to increase physical activity in early PD could potentially modify the disease course.
•Self-reported physical activity declines over time in early Parkinson's disease.•Higher self-reported activity levels are associated with slower motor progression.•Higher self-reported activity is associated with slower non-motor symptom decline.
There are no treatments that convincingly slow the progression of Parkinson’s disease. One avenue of investigation is based on iron deposition in the brain, which occurs with aging but is also ...implicated in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis.
1
Iron levels are regulated by binding to transferrin and ferritin, and intracellular iron is partitioned in neurons to prevent toxic effects. Ferroptosis refers to iron-dependent toxicity that triggers lipid peroxidation and other oxidative stresses that lead to cell death.
2
Furthermore, cellular iron may exacerbate aggregation of α-synuclein, the neuronal protein that forms Lewy body inclusions . . .
Parkinson's disease (PD) and metabolic syndrome are separate entities that share common underlying pathophysiology. Management strategy for metabolic syndrome is clinically better characterized and ...finding a positive clinical correlation between the two could lead to a better understanding of Parkinson's disease progression and prognosis.
To explore the relationship between progression in PD and metabolic syndrome to characterize the underlying pathophysiology, which could then impact the clinical management of PD.
Using modified NCEP (National Cholesterol Education Program) ATP III (Adult Treatment Plan) criteria, patients enrolled in STEADY-PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine) were classified into one of three categories of metabolic syndrome and compared on PD progression over a period of 3 years.
Participants with metabolic syndrome showed a trend for more progression in terms of PD, as measured by the total Unified Parkinson's Disease Rating Scale (UPDRS), the motor EDL (Experiences of daily living) scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the Montreal Cognitive Assessment (MoCA). A significant trend for decline in MoCA was found in the group with metabolic syndrome (−0.78), compared with those without metabolic syndrome (0.14). Greater decline in MoCA signifies worse outcomes.
The results demonstrate a trend in more clinical progression in PD in subjects with metabolic syndrome. However, results are limited by the sample size and the limited laboratory measurements available. We hope this study will encourage larger sample studies to explore this relationship further.
Objectives
Isradipine is a dihydropyridine calcium channel inhibitor that has demonstrated concentration‐dependent neuroprotective effects in animal models of Parkinson’s disease (PD) but failed to ...show efficacy in a phase 3 clinical trial. The objectives of this study were to model the plasma pharmacokinetics of isradipine in study participants from the phase 3 trial; and, to investigate associations between drug exposure and longitudinal clinical outcome measures of PD progression.
Methods
Plasma samples from nearly all study participants randomized to immediate‐release isradipine 5‐mg twice daily (166 of 170) were collected for population pharmacokinetic modeling. Estimates of isradipine exposure included apparent oral clearance and area under the concentration‐time curve. Isradipine exposure parameters were tested for correlations with 36‐month changes in disease severity clinical assessment scores, and time‐to‐event analyses for initiation of antiparkinson therapy.
Results
Isradipine exposures did not correlate with the primary clinical outcome, changes in the antiparkinson therapy‐adjusted Unified Parkinson’s Disease Rating Scale parts I–III score over 36 months (Spearman rank correlation coefficient, rs: 0.09, P = 0.23). Cumulative levodopa equivalent dose at month 36 was weakly correlated with isradipine plasma clearance (rs: 0.18, P = 0.035). This correlation was sex dependent and significant in males, but not females. Those with higher isradipine exposure had decreased risk of needing antiparkinson treatment over 36 months compared with placebo (hazard ratio: 0.87, 95% CI: 0.78–0.98, P = 0.02).
Interpretation
In this clinical trial, higher isradipine plasma exposure did not affect clinical assessment measures of PD severity but modestly decreased cumulative levodopa equivalent dose and the time needed for antiparkinson treatment initiation.
Trial Registration
ClinicalTrials.gov NCT02168842.
Objective:
Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal ...circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed.
Method:
Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI;
n
= 11) and patients with PD (
n
= 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences.
Results:
Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (
n
= 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals.
Conclusion:
The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.
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