Journal of Parkinson's Disease - Volume 11, issue 2

Authors: Colón-Semenza, Cristina | Fulford, Daniel | Ellis, Terry

Article Type: Research Article

Abstract: Background: People with Parkinson’s disease (PwPD) are less active than their age-matched peers. Non-motor symptoms, specifically, deficient motivation, may influence decision-making for exercise due to the impaired mesolimbic dopaminergic pathway. Objective: The purpose of this study was to determine if effort-based decision-making for physical effort was different in PwPD compared to healthy controls. We sought to determine the relationship between effort-based decision making for exercise and a discrete motor task as well as the impact of components of motivation on decision-making for physical effort in PwPD. Methods: An effort-based decision-making paradigm using a discrete motor task …(button pressing) and a continuous exercise task (cycling) was implemented in 32 PwPD and 23 healthy controls. Components of motivation were measured using the Apathy Scale and the Temporal Experience of Pleasure Scale- Anticipatory Pleasure scale. Results: The presence of Parkinson’s disease (PD) did not moderate decisions for either physical effort task. There was a moderate correlation between decisions for both tasks, within each group. The anticipation of pleasure and apathy were predictors of decisions for both physical effort tasks in PwPD, but not in healthy controls. Conclusion: PwPD responded similarly to effort and reward valuations compared to those without PD. Individuals were consistent in their decisions, regardless of the physical effort task. The anticipation of pleasure and apathy were significant predictors of decisions for exercise in PwPD only. Increased anticipation of pleasure, reduction of apathy, and the use of rewards may enhance engagement in high effort exercise among PwPD. Show more

Keywords: Decision-making, effort, rewards, Parkinson’s disease, exercise, motivation

DOI: 10.3233/JPD-202353

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 725-735, 2021

Authors: Gallagher, Julia | Rick, Jacqueline | Xie, Sharon X. | Martinez-Martin, Pablo | Mamikonyan, Eugenia | Chen-Plotkin, Alice | Dahodwala, Nabila | Morley, James | Duda, John E. | Trojanowski, John Q. | Siderowf, Andrew | Weintraub, Daniel

Article Type: Research Article

Abstract: Background: A composite measure that assesses both cognitive and functional abilities in Parkinson’s disease (PD) would be useful for diagnosing mild cognitive impairment (MCI) and PD dementia (PDD) and as an outcome measure in randomized controlled trials. The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) was designed to assess both cognition and basic-instrumental activities of daily living in Alzheimer’s disease but has not yet been validated in PD. Objective: To validate the CDR-SOB as a composite cognitive-functional measure for PD patients, as well as to assess its sensitivity to change. Methods: The CDR-SOB and a …comprehensive cognitive and functional battery was administered to 101 PD patients at baseline (39 normal cognition [NC], 41 MCI and 21 PDD by expert consensus panel), and re-administered to 64 patients after 1-2 years follow-up (32 NC and 32 cognitive impairment [CI] at baseline). Results: Cross-sectionally, CDR-SOB and domain scores were correlated with corresponding neuropsychological or functional measures and were significantly different between cognitive subgroups both at baseline and at follow-up. In addition, CDR-SOB ROC curves distinguished between normal cognition and dementia with high sensitivity, but did not distinguish well between NC and MCI. Longitudinal changes in the CDR-SOB and domain scores were not significant and were inconsistent in predicting change in commonly-used cognitive and functional tests. Conclusion: The CDR-SOB detects dementia-level cognitive impairment in PD but may not be appropriate for predicting longitudinal combined cognitive-functional changes in patients without significant cognitive impairment at baseline. Show more

Keywords: Cognition, dementia, Parkinson’s disease, rating scale

DOI: 10.3233/JPD-202390

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 737-745, 2021

Authors: Ashraf-ganjouei, Amir | Moradi, Kamyar | Aarabi, Mohammadhadi | Abdolalizadeh, AmirHussein | Kazemi, Seyedeh Zahra | Kasaeian, Amir | Vahabi, Zahra

Article Type: Research Article

Abstract: Background: REM behavior disorder (RBD) can occur in the context of neurodegenerative alpha-synucleinopathies, such as Parkinson’s disease (PD). PD patients with RBD (PD-pRBD) represent more severe symptoms and signs compared with those without RBD (PD-nRBD). On another note, autonomic dysfunction in PD patients is categorized as one of the most prominent non-motor symptoms and has been lately the field of interest in research. Objective: In the current study, we longitudinally studied autonomic dysfunction in PD-pRBD and PD-nRBD groups. Method: This study was conducted on 420 drug-naïve PD patients selected from the Parkinson’s Progression Markers Initiative database. …The RBD Screening Questionnaire was used to define the presence of probable RBD. SCOPA-AUT was used to assess autonomic dysfunction. Additionally, dopamine transporter deficits on [123 I] FP-CIT SPECT imaging was performed for all of the patients. Results: Out of 420 PD patients, 158 individuals (37.6%) were considered to have probable RBD (PD-pRBD) and others without RBD (PD-nRBD). Except for pupillomotor function, all the autonomic symptoms were significantly more severe in PD-pRBD group. In PD-nRBD group, caudate striatal binding ratio was negatively correlated with SCOPA-AUT scores, while no significant correlation was observed in PD-pRBD group. Finally, there was a significant difference considering the longitudinal changes of SCOPA-AUT total between PD-pRBD and PD-nRBD groups, suggesting a more severe autonomic decline in PD-pRBD patients. Conclusion: Our results indicate that PD-pRBD patients have more severe autonomic dysfunction. These results support the theory that PD patients can be categorized based on the clinical presentation, possibly representing differences in the disease pathophysiology. Show more

Keywords: Autonomic dysfunction, Parkinson’s disease, REM behavior disorder

DOI: 10.3233/JPD-202134

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 747-755, 2021

Authors: Tropea, Thomas F. | Amari, Noor | Han, Noah | Rick, Jacqueline | Suh, EunRan | Akhtar, Rizwan S. | Dahodwala, Nabila | Deik, Andres | Gonzalez-Alegre, Pedro | Hurtig, Howard | Siderowf, Andrew | Spindler, Meredith | Stern, Matthew | Thenganatt, Mary Ann | Weintraub, Daniel | Willis, Allison W. | Van Deerlin, Vivianna | Chen-Plotkin, Alice

Article Type: Research Article

Abstract: Background: Observational studies in Parkinson’s disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. Objective: To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. Methods: All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options …for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. Results: Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). Conclusions: We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization. Show more

Keywords: Parkinson’s disease, LRRK2, GBA, clinical protocols

DOI: 10.3233/JPD-202406

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 757-765, 2021

Authors: Amundsen-Huffmaster, Sommer L. | Petrucci, Matthew N. | Linn-Evans, Maria E. | Chung, Jae Woo | Howell, Michael J. | Videnovic, Aleksandar | Tuite, Paul J. | Cooper, Scott E. | MacKinnon, Colum D.

Article Type: Research Article

Abstract: Background: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson’s disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. Objective: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. …Methods: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n  = 22) and normal REM sleep muscle tone (PD-RSWA-, n  = 19). Gait characteristics were compared between groups and correlated to RSWA. Results: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. Conclusion: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD. Show more

Keywords: Parkinson’s disease, REM sleep without atonia, gait

DOI: 10.3233/JPD-202098

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 767-778, 2021

Authors: Dion, Catherine | Frank, Brandon E. | Crowley, Samuel J. | Hizel, Loren P. | Rodriguez, Katie | Tanner, Jared J. | Libon, David J. | Price, Catherine C.

Article Type: Research Article

Abstract: Background: A companion paper (Crowley et al., 2020) reports on the neuroimaging and neuropsychological profiles of statistically determined idiopathic non-dementia Parkinson’s disease (PD). Objective: The current investigation sought to further examine subtle behavioral clock drawing differences within the same PD cohort by comparing 1) PD to non-PD peers on digitally acquired clock drawing latency and graphomotor metrics, and 2) PD memory, executive, and cognitively well phenotypes on the same variables. Methods: 230 matched participants (115 PD, 115 non-PD) completed neuropsychological tests and dCDT. Statistically-derived PD cognitive phenotypes characterized PD participants as PD low executive (PDExe; …n  = 25), PD low memory (PDMem; n  = 34), PD cognitively well (PDWell; n  = 56). Using a Bayesian framework and based on apriori hypotheses, we compared groups on: total completion time (TCT), pre-first hand latency (PFHL), post-clock face latency (PCFL), total clock face area (TCFA), and total number of pen strokes. Results: Fewer strokes and slower performance to command were associated with higher odds of PD diagnosis, while a larger clock face in the copy condition was associated with lower odds of PD diagnosis. Within PD cognitive phenotypes, slower performance (TCT, PCFL) and smaller clock face to command were associated with higher odds of being PDExe than PDWell, whereas larger clock faces associated with higher odds of being PDMem than PDWell. Longer disease duration, more pen strokes (command) and smaller clocks (command) associated with higher odds of being PDExe than PDWell. Conclusion: Digitally-acquired clock drawing profiles differ between PD and non-PD peers, and distinguish PD cognitive phenotypes. Show more

Keywords: Parkinson’s disease, bayesian analysis, executive function, memory, propensity score analysis

DOI: 10.3233/JPD-202399

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 779-791, 2021

Authors: Deischinger, Carola | Dervic, Elma | Kaleta, Michaela | Klimek, Peter | Kautzky-Willer, Alexandra

Article Type: Research Article

Abstract: Background: In general, the risk to develop Parkinson’s disease (PD) is higher in men compared to women. Besides male sex and genetics, research suggests diabetes mellitus (DM) is a risk factor for PD as well. Objective: In this population-level study, we aimed at investigating the sex-specific impact of DM on the risk of developing PD. Methods: Medical claims data were analyzed in a cross-sectional study in the Austrian population between 1997 and 2014. In the age group of 40–79 and 80+, 235,268 patients (46.6%females, 53.4%males) with DM were extracted and compared to 1,938,173 non-diabetic controls (51.9%females, …48.1%males) in terms of risk of developing PD. Results: Men with DM had a 1.46 times increased odds ratio (OR) to be diagnosed with PD compared to non-diabetic men (95%CI 1.38–1.54, p  < 0.001). The association of DM with newly diagnosed PD was significantly greater in women (OR = 1.71, 95%CI 1.60–1.82, p  < 0.001) resulting in a relative risk increase of 1.17 (95%CI 1.11–1.30) in the age group 40 to 79 years. In 80+-year-olds the relative risk increase is 1.09 (95%CI 1.01–1.18). Conclusion: Although men are more prone to develop PD, women see a higher risk increase in PD than men amongst DM patients. Show more

Keywords: Diabetes mellitus, Parkinson’s disease, women’s health, sex differences

DOI: 10.3233/JPD-202486

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 793-800, 2021

Authors: Senkevich, Konstantin | Bandres-Ciga, Sara | Yu, Eric | Liyanage, Upekha E. | International Parkinson Disease Genomics Consortium (IPDGC) | Noyce, Alastair J | Gan-Or, Ziv

Article Type: Research Article

Abstract: Background: Epidemiological data suggest that cancer patients have a reduced risk of subsequent Parkinson’s disease (PD) development, but the prevalence of PD in melanoma patients is often reported to be increased. Causal relationships between cancers and PD have not been fully explored. Objective: To study causal relationship between different cancers and PD. Methods: We used GWAS summary statistics of 15 different types of cancers and two-sample Mendelian randomization to study the causal relationship with PD. Results: There was no evidence to support a causal relationship between the studied cancers and PD. We also performed …reverse analyses between PD and cancers with available full summary statistics (melanoma, breast, prostate, endometrial and keratinocyte cancers) and did not find evidence of causal relationship. Conclusion: We found no evidence to support a causal relationship between cancers and PD and the previously reported associations could be a result of genetic pleiotropy, shared biology or biases. Show more

Keywords: Parkinson’s disease, mendelian randomization, cancer, melanoma

DOI: 10.3233/JPD-202474

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 801-809, 2021

Authors: Contin, Manuela | Lopane, Giovanna | Cortelli, Pietro | Sambati, Luisa | Mohamed, Susan | Calandra-Buonaura, Giovanna

Article Type: Research Article

Abstract: Background: Differential diagnosis between Parkinson’s disease (PD) and atypical parkinsonisms (APs) may be difficult at disease onset. The response to levodopa (LD) is a key supportive feature but its definition is largely empirical. Studies evaluating this issue by quantitative tests are scanty. Objective: We aimed to assess the utility of a subacute low LD dose kinetic-dynamic test in the differential diagnosis between PD and APs. It was applied at the baseline of a prospective follow-up in patients with parkinsonian signs within three years of disease motor onset (“BoProPark” cohort) and eventually diagnosed as PD or APs according to …consensus criteria. Methods: Patients under at least 3-month LD therapy received a first morning fasting dose of LD/benserazide or carbidopa (100/25 mg) and underwent simultaneous serial assessments of plasma LD concentration and alternate finger tapping frequency up to 3 h. The main outcome was the extent of LD motor response, calculated by the area under the 3 h tapping effect–time curve (AUC_ETap). A receiver operating characteristic (ROC) curve analysis was performed to establish the optimal AUC_ETap cut-off to differentiate PD and APs. Results: The first 100 consecutive “BoProPark” patients were analyzed. Forty-seven patients were classified as possible, 37 as probable PD and 16 as APs. AUC_ETap medians were similar in the PD subgroups but reduced to a third in APs (p  < 0.001). The optimal AUC_ETap cut-off value was >2186 [(tap/min) x min], with a sensitivity of 92% and a specificity of 75%. Accuracy of the test was 0.85 (95% CI 0.74–0.95), p  < 0.0001. Conclusion: The estimation of 3 h AUC_ETap after a subacute low LD dose proved a reliable, objective tool to assess LD motor response in our cohort of patients. AUC_ETap value rounded to ≥2200 supports PD diagnosis, while lower values may alert to AP diagnoses. Show more

Keywords: Keywords: Levodopa, Parkinson’s disease, atypical parkinsonisms, alternate finger tapping test, kinetics-dynamics

DOI: 10.3233/JPD-202262

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 811-819, 2021

Authors: Bacelis, Jonas | Compagno, Michele | George, Sonia | Pospisilik, J. Andrew | Brundin, Patrik | Naluai, Åsa Torinsson | Brundin, Lena

Article Type: Research Article

Abstract: Background: Rheumatoid arthritis (RA) and the genetic risk landscape of autoimmune disorders and Parkinson’s disease (PD) overlap. Additionally, anti-inflammatory medications used to treat RA might influence PD risk. Objective: To use a population-based approach to determine if there is an association between pre-occurring rheumatoid arthritis (RA) and later-life risk of PD. Methods: The study population was 3.6 million residents of Sweden, who were alive during part or all of the follow-up period; 1997–2016. We obtained diagnoses from the national patient registry and identified 30,032 PD patients, 8,256 of whom each was matched to ten controls based …on birth year, sex, birth location, and time of follow-up. We determined the risk reduction for PD in individuals previously diagnosed with RA. We also determined if the time (in relation to the index year) of the RA diagnosis influenced PD risk and repeated the analysis in a sex-stratified setting. Results: Individuals with a previous diagnosis of RA had a decreased risk of later developing PD by 30–50% compared to individuals without an RA diagnosis. This relationship was strongest in our conservative analysis, where the first PD diagnosis occurred close to the earliest PD symptoms (odds ratio 0.47 (CI 95% 0.28–0.75, p  = 0.0006); with the greatest risk reduction in females (odds ratio 0.40 (CI 95% 0,19–0.76, p  = 0.002). Discussion: Our findings provide evidence that individuals diagnosed with RA have a significantly lower risk of developing PD than the general population. Our data should be considered when developing or repurposing therapies aimed at modifying the course of PD. Show more

Keywords: Rheumatoid arthritis, Parkinson’s disease, autoimmune disease, anti-inflammatory

DOI: 10.3233/JPD-202418

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 821-832, 2021