and

Hot Keywords
Ageing Neurodegenerative Diseases Neurodegeneration AD

Top

Ten articles on Parkinson’s disease published on npj Parkinson's Disease

Published on: 14 Jul 2021 Viewed: 483

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series. This week, we would like to share 10 picks on Parkinson's disease.

Title: Parkinson's disease multimodal imaging: F-DOPA PET, neuromelanin-sensitive and quantitative iron-sensitive MRI
Authors: Frédérique Depierreux, Eric Parmentier, Laurane Mackels, Katherine Baquero, Christian Degueldre, Evelyne Balteau, Eric Salmon, Christophe Phillips, Mohamed Ali Bahri, Pierre Maquet, Gaëtan Garraux
Type: Article from npj Parkinson's Disease
Abstract:
Parkinson’s disease (PD) is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin (NM)-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How regional NM loss and iron accumulation within specific areas of SN relate to nigro-striatal dysfunction needs to be clarified. We measured dopaminergic function in pre- and postcommissural putamen by [18F]DOPA PET in 23 Parkinson’s disease patients and 23 healthy control (HC) participants in whom NM content and iron load were assessed in medial and lateral SN, respectively, by NM-sensitive and quantitative R2* MRI. Data analysis consisted of voxelwise regressions testing the group effect and its interaction with NM or iron signals. In PD patients, R2* was selectively increased in left lateral SN as compared to healthy participants, suggesting a local accumulation of iron in Parkinson’s disease. By contrast, NM signal differed between PD and HC, without specific regional specificity within SN. Dopaminergic function in posterior putamen decreased as R2* increased in lateral SN, indicating that dopaminergic function impairment progresses with iron accumulation in the SN. Dopaminergic function was also positively correlated with NM signal in lateral SN, indicating that dopaminergic function impairment progresses with depigmentation in the SN. A complex relationship was detected between R2* in the lateral SN and NM signal in the medial SN. In conclusion, multimodal imaging reveals regionally specific relationships between iron accumulation and depigmentation within the SN of Parkinson’s disease and provides in vivo insights in its neuropathology.
Access this article: https://doi.org/10.1038/s41531-021-00198-3


Title: TOMM40 ‘523’ poly-T repeat length is a determinant of longitudinal cognitive decline in Parkinson's disease
Authors: Megan C. Bakeberg, Anastazja M. Gorecki, Abigail L. Pfaff, Madison E. Hoes, Sulev Kõks, P. Anthony Akkari, Frank L. Mastaglia, Ryan S. Anderton
Type: Review from npj Parkinson's Disease
Abstract:
The translocase of outer mitochondrial membrane 40 (TOMM40) ‘523’ polymorphism has previously been associated with age of Alzheimer’s disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson’s disease (PD). Therefore, this longitudinal study investigated the role of the ‘523’ variant in cognitive decline in a patient cohort from the Parkinson’s Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 ‘523’ variant using whole-genome sequencing data. Covariate-adjusted generalised linear mixed models were utilised to examine the relationship between TOMM40 ‘523’ allele lengths and cognitive scores, while taking into account the APOE ε genotype. Cognitive scores declined over the 5-year study period and were lower in males than in females. When accounting for APOE ε4, the TOMM40 ‘523’ variant was not robustly associated with overall cognitive performance. However, in APOE ε3/ε3 carriers, who accounted for ~60% of the whole cohort, carriage of shorter ‘523’ alleles was associated with more severe cognitive decline in both sexes, while carriage of the longer alleles in females were associated with better preservation of global cognition and a number of cognitive sub-domains, and with a delay in progression to dementia. The findings indicate that when taken in conjunction with the APOE genotype, TOMM40 ‘523’ allele length is a significant independent determinant and marker for the trajectory of cognitive decline and risk of dementia in PD.
Access this article: https://doi.org/10.1038/s41531-021-00200-y


Title: Parkinson's disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration
Authors: G. Carola, D. Malagarriga, C. Calatayud, M. Pons-Espinal, L. Blasco-Agell, Y. Richaud-Patin, I. Fernandez-Carasa, V. Baruffi, S. Beltramone, E. Molina, P. Dell’Era, J. J. Toledo-Aral, E. Tolosa, A. R. Muotri, J. Garcia Ojalvo, J. Soriano, A. Raya, A. Consiglio
Type: Article from npj Parkinson's Disease
Abstract:
A deeper understanding of early disease mechanisms occurring in Parkinson’s disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients’ networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases.
Access this article: https://doi.org/10.1038/s41531-021-00198-3


Title: A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson's disease
Authors: Camilla Christina Pedersen, Johannes Lange, Marthe Gurine Gunnarsdatter Førland, Angus D. Macleod, Guido Alves, Jodi Maple-Grødem
Type: Review Article from npj Parkinson's Disease
Abstract:
There is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson’s disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression. This systematic review aimed to summarize all available primary research reporting the association of SNCA polymorphisms with features of PD. We systematically searched PubMed and Web of Science, from inception to 1 June 2020, for studies evaluating the association of common SNCA variants with age at onset (AAO) or any clinical feature attributed to PD in patients with idiopathic PD. Fifty-eight studies were included in the review that investigated the association between SNCA polymorphisms and a broad range of outcomes, including motor and cognitive impairment, sleep disorders, mental health, hyposmia, or AAO. The most reproducible findings were with the REP1 polymorphism or rs356219 and an earlier AAO, but no clear associations were identified with an SNCA polymorphism and any individual clinical outcome. The results of this comprehensive summary suggest that, while there is evidence that genetic variance in the SNCA region may have a small impact on clinical outcomes in PD, the mechanisms underlying the association of SNCA polymorphisms with PD risk may not be a major factor driving clinical heterogeneity in PD.
Access this article: https://doi.org/10.1038/s41531-021-00196-5


Title: Impaired reach-to-grasp kinematics in parkinsonian patients relates to dopamine-dependent, subthalamic beta bursts
Authors: Matteo Vissani, Chiara Palmisano, Jens Volkmann, Gianni Pezzoli, Silvestro Micera, Ioannis U. Isaias, Alberto Mazzoni
Type: Article from npj Parkinson's Disease
Abstract:
Excessive beta-band oscillations in the subthalamic nucleus are key neural features of Parkinson’s disease. Yet the distinctive contributions of beta low and high bands, their dependency on striatal dopamine, and their correlates with movement kinematics are unclear. Here, we show that the movement phases of the reach-to-grasp motor task are coded by the subthalamic bursting activity in a maximally-informative beta high range. A strong, three-fold correlation linked beta high range bursts, imbalanced inter-hemispheric striatal dopaminergic tone, and impaired inter-joint movement coordination. These results provide new insight into the neural correlates of motor control in parkinsonian patients, paving the way for more informative use of beta-band features for adaptive deep brain stimulation devices.
Access this article: https://doi.org/10.1038/s41531-021-00187-6


Title: Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson’s disease
Authors: Christina Andica, Koji Kamagata, Yuya Saito, Wataru Uchida, Shohei Fujita, Akifumi Hagiwara, Toshiaki Akashi, Akihiko Wada, Takashi Ogawa, Taku Hatano, Nobutaka Hattori, Shigeki Aoki
Type: Article from npj Parkinson's Disease
Abstract:
Using a fixel-based analysis (FBA), we assessed the fiber-specific white matter (WM) alterations in nonmedicated patients with early-stage Parkinson’s disease (PD) with tremor-dominant (TD; n = 53; mean age, 61.7 ± 8.7 years) and postural instability and gait disorder (PIGD; n = 27; mean age, 57.8 ± 8.1 years) motor subtypes and age- and sex-matched healthy controls (HC; n = 43; mean age, 61.6 ± 9.2 years) from Parkinson’s Progression Markers Initiative dataset. FBA revealed significantly increased macrostructural fiber cross section and a combination of fiber density and cross section metrics within the corticospinal tract in patients with TD-PD compared with HC. Nonetheless, no significant changes in FBA-derived metrics were found in patients with PIGD-PD compared with HC or patients with TD-PD. Our results may provide evidence of WM neural compensation mechanisms in patients with TD-PD marked by increases in fiber bundle size and the ability to relay information between brain regions.
Access this article: https://doi.org/10.1038/s41531-021-00197-4


Title: Long-term effect of apomorphine infusion in advanced Parkinson's disease: a real-life study
Authors: Bruna Meira, Bertrand Degos, Elise Corsetti, Mohamed Doulazmi, Emeline Berthelot, Clara Virbel-Fleischman, Pauline Dodet, Aurélie Méneret, Louise-Laure Mariani, Cécile Delorme, Florence Cormier-Dequaire, David Bendetowicz, Nicolas Villain, Clément Tarrano, Lise Mantisi, Hélène Letrillart, Céline Louapre, Eavan McGovern, Yulia Worbe, David Grabli, Marie Vidailhet, Elodie Hainque, Emmanuel Roze
Type: Article from npj Parkinson's Disease
Abstract:
Long-term effects of continuous subcutaneous apomorphine infusion (CSAI) on health-related quality of life (HRQoL) and predictors of CSAI discontinuation are poorly known. Data from consecutive advanced Parkinson’s disease patients treated in routine care were retrospectively collected over 24 months after CSAI initiation, with a focus on the 39-item Parkinson’s disease questionnaire (PDQ-39). We determined predictors of CSAI discontinuation and HRQoL improvement using multiple regression analysis. Of the 110 subjects evaluated over a 2-year period, 35% discontinued CSAI. Of those who continued treatment, HRQoL remained stable with a sustained reduction in motor fluctuations. The observed effect on dyskinesias was mild and transient. Of note, patients with preexisting impulse control disorders showed an overall good tolerability. PDQ-39 was the only baseline predictor of HRQoL improvement after 2 years of treatment. The presence of dyskinesias, poorer psychological status, shorter disease duration, male sex, and worse OFF state were predictors of discontinuation. Best candidates for CSAI are patients with: (i) poor baseline HRQoL and (ii) marked motor fluctuations.
Access this article: https://doi.org/10.1038/s41531-021-00194-7


Title: A randomised controlled trial on effectiveness and feasibility of sport climbing in Parkinson's disease
Authors: Agnes Langer, Sebastian Hasenauer, Anna Flotz, Lucia Gassner, Rochus Pokan, Peter Dabnichki, Laurenz Wizany, Jakob Gruber, Dominik Roth, Sarah Zimmel, Marco Treven, Michaela Schmoeger, Ulrike Willinger, Walter Maetzler, Heidemarie Zach
Type: Article from npj Parkinson's Disease
Abstract:
Physical activity is of prime importance in non-pharmacological Parkinson’s disease (PD) treatment. The current study examines the effectiveness and feasibility of sport climbing in PD patients in a single-centre, randomised controlled, semi-blind trial. A total of 48 PD patients without experience in climbing (average age 64 ± 8 years, Hoehn & Yahr stage 2–3) were assigned either to participate in a 12-week sport climbing course (SC) or to attend an unsupervised physical training group (UT). The primary outcome was the improvement of symptoms on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III). Sport climbing was associated with a significant reduction of the MDS-UPDRS-III (−12.9 points; 95% CI −15.9 to −9.8), while no significant improvement was to be found in the UT (−3.0 points; 95% CI −6.0 to 0.1). Bradykinesia, rigidity and tremor subscales significantly improved in SC, but not in the unsupervised control group. In terms of feasibility, the study showed a 99% adherence of participants to climbing sessions and a drop-out rate of only 8%. No adverse events occurred. This trial provides class III evidence that sport climbing is highly effective and feasible in mildly to moderately affected PD patients.
Access this article: https://doi.org/10.1038/s41531-021-00193-8


Title: Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease
Authors: Stefanie T. Jost, Veerle Visser-Vandewalle, Alexandra Rizos, Philipp A. Loehrer, Monty Silverdale, Julian Evans, Michael Samuel, Jan Niklas Petry-Schmelzer, Anna Sauerbier, Alexandra Gronostay, Michael T. Barbe, Gereon R. Fink, Keyoumars Ashkan, Angelo Antonini, Pablo Martinez-Martin, K. Ray Chaudhuri, Lars Timmermann, Haidar S. Dafsari, EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson’s Disease Study Group
Type: Article from npj Parkinson's Disease
Abstract:
To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.
Access this article: https://doi.org/10.1038/s41531-021-00174-x

Title: Balance response to levodopa predicts balance improvement after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease
Authors: Zixiao Yin, Yutong Bai, Liangying Zou, Xin Zhang, Huimin Wang, Dongmei Gao, Guofan Qin, Ruoyu Ma, Kai Zhang, Fangang Meng, Yin Jiang, Anchao Yang, Jianguo Zhang
Type: Article from npj Parkinson's Disease
Abstract:
The effect of subthalamic nucleus deep brain stimulation (STN-DBS) on balance function in patients with Parkinson’s disease (PD) and the potential outcome predictive factors remains unclear. We retrospectively included 261 PD patients who underwent STN-DBS and finished the 1-month follow-up (M1) assessment in the explorative set for identifying postoperative balance change predictors, and 111 patients who finished both the M1 and 12-month follow-up (M12) assessment in the validation set for verifying the identified factors. Motor and balance improvement were evaluated through the UPDRS-III and the Berg balance scale (BBS) and pull test (PT), respectively. Candidate predictors of balance improvement included age, disease duration, motor subtypes, baseline severity of PD, cognitive status, motor and balance response to levodopa, and stimulation parameters. In the off-medication condition, STN-DBS significantly improved BBS and PT performance in both the M1 and M12, in both datasets. While in the on-medication condition, no significant balance improvement was observed. Higher preoperative BBS response to levodopa was significantly associated with larger postoperative off-medication, but not on-medication, BBS (p < 0.001) and PT (p < 0.001) improvement in both the M1 and M12. BBS subitems 8, 9, 11, 13, and 14 were the major contributors to the prediction of balance improvement after STN-DBS. STN-DBS improves short-term off-medication, but not on-medication, balance function assessed through BBS and PT. Preoperative BBS response to levodopa best predicts postoperative off-medication balance improvement. For patients who manifested severe balance problems, a levodopa challenge test on BBS or the short version of BBS is recommended.
Access this article: https://doi.org/10.1038/s41531-021-00192-9

© 2016-2023 OAE Publishing Inc., except certain content provided by third parties