Journal of Parkinson's Disease - Volume 13, issue 3

Authors: Peter, Inga | Strober, Warren

Article Type: Review Article

Abstract: Emerging evidence implicates intestinal involvement in the onset and/or progression on the selective degeneration of dopaminergic neurons characterizing Parkinson’s disease (PD). On the one hand, there are studies supporting the Braak hypothesis that holds that pathologic α-synuclein, a hallmark of PD, is secreted by enteric nerves into intestinal tissue and finds its way to the central nervous system (CNS) via retrograde movement in the vagus nerve. On the other hand, there is data showing that cells bearing leucine-rich repeat kinase 2 (LRRK2), a signaling molecule with genetic variants associated with both PD and with inflammatory bowel disease, can be activated …in intestinal tissue and contribute locally to intestinal inflammation, or peripherally to PD pathogenesis via cell trafficking to the CNS. Importantly, these gut-centered factors affecting PD development are not necessarily independent of one another: they may interact and enhance their respective pathologic functions. In this review, we discuss this possibility by analysis of studies conducted in recent years focusing on the ability of LRRK2 to shape immunologic responses and the role of α-synuclein in influencing this ability. Show more

Keywords: Gut-brain axis, intestinal inflammation, LRRK2, Parkinson’s disease, α-synuclein, enteric nervous system

DOI: 10.3233/JPD-230021

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 279-296, 2023

Authors: Chahine, Lana M. | Merchant, Kalpana | Siderowf, Andrew | Sherer, Todd | Tanner, Caroline | Marek, Kenneth | Simuni, Tanya

Article Type: Review Article

Abstract: The Parkinson’s disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal α-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early …stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD. Show more

Keywords: Parkinson’s disease, disease staging, biomarkers, alpha-synuclein

DOI: 10.3233/JPD-225111

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 297-309, 2023

Authors: Oosterhof, Thomas H. | Schootemeijer, Sabine | de Vries, Nienke M.

Article Type: Other

Abstract: Despite increasing evidence on exercise in Parkinson’s disease (PD) it remains unclear what type and intensity of exercise are most effective. Currently, most evidence favors moderate- to high-intensity aerobic exercise for its positive effects on motor symptoms as well as disease modifying potential. On the other hand, observational studies have shown that the sheer volume of exercise matters as well, independent of intensity. So far, the efficacy of the volume of exercise has not been confirmed by randomized controlled trials (RCTs). Here, we provide an overview of the ongoing RCTs that promote physical activity in daily life in PD. We …found seven RCTs with sample sizes between 30 and 452 and a follow-up between 4 weeks and 12 months. Steps per day is the most commonly reported primary outcome measure. The ongoing RCTs will provide evidence for feasibility, whereafter the PD research field is ready for a next step and to explore the effect of physical activity on disease progression and PD symptoms. Show more

DOI: 10.3233/JPD-239001

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 311-322, 2023

Authors: Alonso-Canovas, Araceli | Voeten, Jos | Gifford, Larry | Thomas, Omotola | Lees, Andrew J. | Bloem, Bastiaan R.

Article Type: Article Commentary

Abstract: The discovery of levodopa in the late 60 s of twentieth century was a ‘golden moment’ for people with Parkinson’s disease (PD). Unfortunately, clinical experience showed that some symptoms escaped from symptomatic control, and long-term complications developed. Back then, neurologists coined the term “honeymoon period” for the early phase of uncomplicated response to levodopa, and it continues to be used in scientific literature. However, medical terms are no longer restricted to professionals, and few people with PD relate to the notion of a “honeymoon”. We examine the reasons why this term, once helpful, but inaccurate and inappropriate, should be abandoned.

Keywords: Honeymoon, Parkinson’s disease, personalized medicine, patient-centeredness

DOI: 10.3233/JPD-225064

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 323-328, 2023

Authors: Mathur, Soania | LaMonica, Kristi | Matthews, Helen | Hill, Kat

Article Type: Article Commentary

Abstract: There is a fundamental gap in knowledge in how Parkinson’s disease manifests and affects women throughout their hormonal life cycle, resulting in unmet needs and adversely impacting women’s quality of life. A set of questionnaires was developed and deployed through Fox Insight (open access) to address these issues by gathering data. This is the data from the first survey. The data from the questions regarding self-image were striking. 61% of women report that their Parkinson’s disease negatively impacts their self-image. Here we explore the negative impact of Parkinson’s disease on women to begin to fill the gaps in knowledge.

Keywords: Hormones, life-stage, menopause, Parkinson’s disease, peri-menopause, post-menopausal, pre-menopause, self-image, women

DOI: 10.3233/JPD-230017

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 329-332, 2023

Authors: Tremblay, Cécilia | Serrano, Geidy E. | Dunckley, Nathaniel | Zhang, Nan | Fiock, Kimberly L. | Adler, Charles H. | Driver-Dunckley, Erika | Mehta, Shyamal H. | Shill, Holly A. | Beach, Thomas G.

Article Type: Research Article

Abstract: Background: Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations. Objective: This study aimed to assess postmortem cerebellar volume in subjects with or without ET, as compared with subjects with multiple system atrophy (MSA), a well-established cerebellar neurodegeneration. Methods: Cases with ET (n  = 29), MSA (n  = 7), and non-demented control cases without any movement disorder (n  = 22) were selected from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a …longitudinal clinicopathological study with annual research-dedicated clinical assessments by neuropsychologists, subspecialist movement disorders, and cognitive/behavioral neurologists, with comprehensive neuropathological examinations after death. Group comparisons were controlled for common age-related neurodegenerative and cerebrovascular pathologies. Cerebellar volumes were calculated using digital images of slices taken at the time of autopsy, immediately after brain removal and before fixation. Results: Cerebellar volume was not reduced in ET subjects compared to controls. The two groups did not differ in terms of incidental cerebrovascular and Alzheimer’s disease neuropathology. In contrast, cerebellar volume was significantly reduced in subjects with MSA when compared to ET and control subjects. Conclusion: In a well-characterized cohort, postmortem cerebellar volume measurements suggest that there are no volume alterations in ET when compared to controls, in contrast to significant cerebellar atrophy in subjects with MSA. Show more

Keywords: Essential tremor, movement disorder, multiple system atrophy, autopsy, atrophy, Purkinje cell, neuropathology

DOI: 10.3233/JPD-225033

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 333-340, 2023

Authors: Peball, Marina | Valent, Dora | Grossauer, Anna | Marini, Kathrin | Ellmerer, Philipp | Wallnöfer, Jonas | Krismer, Florian | Djamshidian, Atbin | Seppi, Klaus | Heim, Beatrice

Article Type: Research Article

Abstract: Background: Sarcopenia is characterized by a progressive loss of muscle mass, strength, and function resulting in adverse health outcomes. Current assessment strategies are bothersome and means to simplify the diagnosis are an unmet medical need in Parkinson’s disease (PD). Objective: To evaluate temporal muscle thickness (TMT) obtained on routine cranial MRI as a surrogate marker of sarcopenia in PD patients. Methods: We correlated TMT from axial non-contrast-enhanced T1-weighted sequences of MRI close (±12 months) to an outpatient visit including sarcopenia (EWGSOP1, EWGSOP2, SARC-F), frailty (Fried’s criteria, clinical frailty scale), and disease characteristics of Parkinson’s patients (Hoehn …and Yahr-scale, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, quality of life with the Parkinson’s Disease Questionnaire-8) assessments. Results: Cranial MRI was available in 32 patients with a mean age of 73.56±5.14 years, mean disease duration of 11.46±5.66 years, and median Hoehn and Yahr stage of 2.5. The mean TMT was 7.49±2.76 (7.15) mm. Mean TMT was significantly associated with sarcopenia (EWGSOP2, p  = 0.018; EWGSOP1, p  = 0.023) and frailty status (physical phenotype; p  = 0.045). Moreover, there were significant moderate to strong correlations between TMT measurement and appendicular skeletal muscle mass index (r : 0.437, p  = 0.012), as well as handgrip strength (r : 0.561, p  < 0.001). Conclusion: Reduced TMT seems to be a promising surrogate marker for sarcopenia (EWGSOP2) and muscle strength in this pilot study in PD patients. Show more

Keywords: Temporal muscle thickness, sarcopenia, Parkinson’s disease, frailty, biomarker

DOI: 10.3233/JPD-225108

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 341-350, 2023

Authors: Memon, Adeel A. | Catiul, Corina | Irwin, Zachary | Pilkington, Jennifer | Memon, Raima A. | Joop, Allen | Wood, Kimberly H. | Cutter, Gary | Miocinovic, Svjetlana | Amara, Amy W.

Article Type: Research Article

Abstract: Background: Sleep disorders are common in Parkinson’s disease (PD) and include alterations in sleep-related EEG oscillations. Objective: This case-control study tested the hypothesis that patients with PD would have a lower density of Scalp-Slow Wave (SW) oscillations and higher slow-to-fast frequencies ratio in rapid eye movement (REM) sleep than non-PD controls. Other sleep-related quantitative EEG (qEEG) features were also examined, including SW morphology, sleep spindles, and Scalp-SW spindle phase-amplitude coupling. Methods: Polysomnography (PSG)-derived sleep EEG was compared between PD participants (n  = 56) and non-PD controls (n  = 30). Following artifact rejection, sleep qEEG analysis was performed in …frontal and central leads. Measures included SW density and morphological features of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in Non-REM (NREM) and REM. Differences in qEEG features between PD and non-PD controls were compared using two-tailed Welch’s t -tests, and correction for multiple comparisons was performed per the Benjamini-Hochberg method. Results: SW density was lower in PD than in non-PD controls (F = 13.5, p ’ = 0.003). The PD group also exhibited higher ratio of slow REM EEG frequencies (F = 4.23, p ’ = 0.013), higher slow spindle peak frequency (F = 24.7, p ’ < 0.002), and greater SW-spindle coupling angle distribution non-uniformity (strength) (F = 7.30, p ’ = 0.034). Conclusion: This study comprehensively evaluates sleep qEEG including SW-spindle phase amplitude coupling in PD compared to non-PD controls. These findings provide novel insights into how neurodegenerative disease disrupts electrophysiological sleep rhythms. Considering the role of sleep oscillatory activity on neural plasticity, future studies should investigate the influence of these qEEG markers on cognition in PD. Show more

Keywords: Parkinson’s disease, quantitative sleep EEG, non-rapid eye movement sleep, slow waves, sleep spindles, phase-amplitude coupling, rapid eye movement sleep

DOI: 10.3233/JPD-223565

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 351-365, 2023

Authors: Freidle, Malin | Thompson, William H. | Albrecht, Franziska | Franzén, Erika

Article Type: Research Article

Abstract: Background: Deficits in motor learning could be an important explanation for the balance and gait impairments characteristic of people with Parkinson’s disease (PD). Empirical studies often report that so-called implicit motor sequence learning is impaired in people with PD, but the results are inconclusive. Altered brain activity during implicit motor sequence learning has also been reported for people with PD in comparison to healthy individuals. Objective: To investigate implicit motor sequence learning and associated neural correlates in individuals with mild to moderate PD. Methods: Fifty-seven participants with PD and 34 healthy participants, all ≥60 years of …age, performed the serial reaction time task (SRTT) during the acquisition of functional magnetic resonance imaging (fMRI) data. We analyzed the SRTT as a measure of implicit motor sequence learning in two complementary ways. We analyzed the task-induced fMRI data within regions of interest (ROIs) as well as functional connectivity between ROIs. Results: We found a significant group difference in SRTT performance indicating that the participants with PD had a somewhat lower level of implicit motor sequence learning than the healthy participants. Exploratory analyses suggested that impairments in implicit motor sequence learning for people with PD might be due to a lower learning rate. We did not find any significant group differences in the fMRI data. Conclusion: Our exploratory finding of a lower implicit motor learning rate in PD could have important implications for how people with PD should practice new motor tasks and physical exercise. Future studies need to confirm this finding with hypothesis-driven analyses. Show more

Keywords: Cerebellum, corpus striatum, learning, magnetic resonance imaging, motor cortex, motor skills, Parkinson’s disease

DOI: 10.3233/JPD-223480

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 367-378, 2023

Authors: Santos-García, Diego | de Deus Fonticoba, Teresa | Cores Bartolomé, Carlos | Feal Painceiras, Maria J. | Íñiguez-Alvarado, Maria Cristina | García Díaz, Iago | Jesús, Silvia | Buongiorno, Maria Teresa | Planellas, Lluís | Cosgaya, Marina | García Caldentey, Juan | Caballol, Nuria | Legarda, Ines | Hernández Vara, Jorge | Cabo, Iria | López Manzanares, Lydia | González Aramburu, Isabel | Ávila Rivera, Maria A. | Gómez Mayordomo, Víctor | Nogueira, Víctor | Puente, Víctor | Dotor García-Soto, Julio | Borrué, Carmen | Solano Vila, Berta | Álvarez Sauco, María | Vela, Lydia | Escalante, Sonia | Cubo, Esther | Carrillo Padilla, Francisco | Martínez Castrillo, Juan C. | Sánchez Alonso, Pilar | Alonso Losada, Maria G. | López Ariztegui, Nuria | Gastón, Itziar | Kulisevsky, Jaime | Menéndez González, Manuel | Seijo, Manuel | Ruiz Martínez, Javier | Valero, Caridad | Kurtis, Mónica | González Ardura, Jessica | Alonso Redondo, Ruben | Ordás, Carlos | López Díaz, Luis M. | McAfee, Darrian | Calopa, Matilde | Carrillo, Fátima | Escamilla Sevilla, Francisco | Freire-Alvarez, Eric | Gómez Esteban, Juan Carlos | García Ramos, Rocío | Luquín, María Rosario Isabel | Martínez-Torres, Irene | Sesar Ignacio, Ángel | Martinez-Martin, Pablo | Mir, Pablo

Article Type: Research Article

Abstract: Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to …assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD. Show more

Keywords: Axial symptoms, cognition, MNCD classification, non-motor symptoms, Parkinson's disease, quality of life

DOI: 10.3233/JPD-225073

Citation: Journal of Parkinson's Disease, vol. 13, no. 3, pp. 379-402, 2023