Journal of Parkinson's Disease - Volume 10, issue 4

Authors: Cubo, Esther | Martínez-Martín, Pablo | González-Bernal, Jerónimo | Casas, Elena | Arnaiz, Sandra | Miranda, Javier | Gámez, Pedro | Santos-García, Diego | Coppadis Study Group:

Collaborators: Adarmes, AD | Almeria, M | Alonso Losada, MG | Alonso Cánovas, A | Alonso Frech, F | Álvarez, I | Álvarez Sauco, M | Aneiros Díaz, A | Arnáiz, S | Arribas, S | Ascunce Vidondo, A | Aguilar, M | Ávila, MA | Bernardo Lambrich, N | Bejr-Kasem, H | Blázquez Estrada, M | Botí, M | Borrue, C | Buongiorno, MT | Cabello González, C | Cabo López, I | Caballol, N | Cámara Lorenzo, A | Carrillo, F | Carrillo Padilla, FJ | Casas, E | Catalán, MJ | Clavero, P | Cortina Fernández, A | Cosgaya, M | Cots Foraster, A | Crespo Cuevas, A | Cubo, E | de Deus Fonticoba, T | de Fábregues-Boixar, O | Díez-Fairen, M | Erro, E | Escalante, S | Estelrich Peyret, E | Fernández Guillán, N | Gámez, P | Gallego, M | García Caldentey, J | García Campos, C | García Moreno, JM | Gastón, I | Gómez Garre, MP | Gómez Mayordomo, V | González Aloy, J | González-Aramburu, I | González Ardura, J | González García, B | González Palmás, MJ | González Toledo, GR | Golpe Díaz, A | Grau Solá, M | Guardia, G | Hernández Vara, J | Horta-Barba, A | Idoate Calderón, D | Infante, J | Jesús, S | Kulisevsky, J | Kurtis, M | Labandeira, C | Labrador, MA | Lacruz, F | Lage Castro, M | Lastres Gómez, S | Legarda, I | López Ariztegui, N | López Díaz, LM | López Manzanares, L | López Seoane, B | Lucas del Pozo, S | Macías, Y | Mata, M | Martí Andres, G | Martí, MJ | Martínez Castrillo, JC | Martinez-Martin, P | McAfee, D | Meitín, MT | Menéndez González, M | Méndez del Barrio, C | Mir, P | Miranda Santiago, J | Morales Casado, MI | Moreno Diéguez, A | Nogueira, V | Novo Amado, A | Novo Ponte, S | Ordás, C | Pagonabarraga, J | Pareés, I | Pascual-Sedano, B | Pastor, P | Pérez Fuertes, A | Pérez Noguera, R | Planas-Ballvé, A | Planellas, L | Prats, MA | Prieto Jurczynska, C | Puente, V | Pueyo Morlans, M | Redondo Rafales, N | Rodríguez Méndez, L | Rodríguez Pérez, AB | Roldán, F | Ruíz De Arcos, M | Ruíz Martínez, J | Sánchez Alonso, P | Sánchez-Carpintero, M | Sánchez Díez, G | Sánchez Rodríguez, A | Santacruz, P | Santos García, D | Segundo Rodríguez, JC | Seijo, M | Sierra Peña, M | Solano Vila, B | Suárez Castro, E | Tartari, JP | Valero, C | Vargas, L | Vela, L | Villanueva, C | Vives, B | Villar, MD

Article Type: Research Article

Abstract: Background: The asymmetry of motor manifestations present in Parkinson’s disease (PD) suggests the existence of differences between both hemispheres. As a consequence, this asymmetry might contribute to different PD clinical phenotypes. Objective: To study the relationship between motor symptom laterality with motor, non-motor symptoms (NMS), freezing of gait (FOG), and quality of life (QoL) impairment in PD. Methods: In this cross-sectional study, we measured motor symptoms severity and complications with the Unified Parkinsons’ disease Rating Scale (UPDRS), FOG with the FOG questionnaire, QoL with the 39-item PD Quality of Life Questionnaire Summary Index, and NMS with …the NMS, Visual Analogue Scales for Pain and Fatigue, Beck Depression Inventory-II, Impulsive-Compulsive Disorders, and PD Sleep and Cognitive Rating scales. We defined left and right motor laterality using the UPDRS part III. We used comparative, regression, and effect size analyses to evaluate the impact of asymmetry on motor and NMS, FOG, and QoL. Results: 342 left (LPD) and 310 right (RPD) patients, with a mean age of 62.0±8.8 years, were included. In multivariate regression analysis, LPD was associated with a greater motor (OR = 1,50, 95% CI 1.02–2.21), FOG (OR = 1.56, 95% CI 1.01–2.41), and overall NMS impairment (OR = 1.43, 95% CI 1.001–2.06), and better QoL (OR = 0.52 95% CI 0.32–0.85). Overall, only a mild effect size was found for all comparisons in which significant differences were present. Conclusion: In this large multicenter study, motor symptom laterality seems to carry a mild but significant impact on PD clinical manifestations, and QoL. Show more

Keywords: Parkinson’s disease, asymmetry, motor, non-motor symptoms, quality of life

DOI: 10.3233/JPD-202067

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1611-1620, 2020

Authors: Vela-Desojo, Lydia | Urso, Daniele | Kurtis-Urra, Monica | García-Ruiz, Pedro J. | Pérez-Fernández, Elia | Lopez-Valdes, Eva | Posada-Rodriguez, Ignacio | Ybot-Gorrin, Isabel | Lopez-Manzanares, Lydia | Mata, Marina | Borrue, Carmen | Ruiz- Huete, Cristina | del Valle, Maria | Martinez-Castrillo, Juan Carlos

Article Type: Research Article

Abstract: Background: Sexual dysfunction (SD) is one of the least studied non-motor symptoms in Parkinson’s disease (PD). Objectives: To assess sexual function in a cohort of patients with early-onset PD (EOPD) and compare it to a group of healthy controls. Methods: In this cross-sectional multicenter study, SD was assessed with gender-specific multi-dimensional self-reported questionnaires: The Brief Male Sexual Function Inventory (BSFI-M) and the Female Sexual Function Index (FSFI). Scores between patients and controls were compared and associations between SD and demographical and clinical variables were studied. Results: One hundred and five patients (mean age 47.35±7.8, …disease duration 6 (3–11) years, UPDRS part III 17 (10–23) and 90 controls were recruited. The BSFI-M total score was lower in EOPD men than in controls, and specific items were also significantly lower, such as drive, erections, ejaculation, and satisfaction. EOPD women had lower scores than controls in total FSFI, and certain domains such as lubrication and pain. SD was present in 70.2% of patients and 52.5% of controls. Sexual satisfaction in 35.2% of patients and 81.2% of controls. By gender, male and female patients had more SD than controls but only male patients had more dissatisfaction than controls. Gender, higher depression scores and urinary dysfunction were associated with SD in multivariate analysis; and gender, UPDRS and urinary dysfunction with sexual satisfaction Conclusion: In this Spanish cohort, SD and sexual dissatisfaction was more prevalent in EOPD patients than in the general population. Gender and urinary disfunction were associated with SD and sexual dissatisfaction. Show more

Keywords: Sexual dysfunction, sexual satisfaction, non-motor symptoms, Parkinson’s disease, EOPD

DOI: 10.3233/JPD-202066

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1621-1629, 2020

Authors: Lennaerts-Kats, Herma | Ebenau, Anne | Steppe, Maxime | van der Steen, Jenny T. | Meinders, Marjan J. | Vissers, Kris | Munneke, Marten | Groot, Marieke | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Background: Family caregivers provide the majority of care for people with Parkinson’s disease (PD) in the palliative care phase. For many this is a demanding experience, affecting their quality of life. Objective: We set out to map the experiences of bereaved family caregivers during the period of informal care in the palliative care phase as well as after the death of their loved one with PD. Methods: Ten bereaved family caregivers participated in this qualitative study. Semi-structured interviews were conducted and interpretative phenomenological analysis was used executed. Results: We identified four main themes. 1) …Feeling like a professional caregiver: while caring for a person with PD, the family caregivers took over many roles and tasks of the person with PD. 2) Healthcare professionals do not always know what PD really means: most interviewees had negative experiences with knowledge and understanding of PD of, especially, (practice) nurses. 3) Being on your own: many respondents had felt highly responsible for their loved one’s care and lacked time and space for themselves. Grief and feelings of guilt were present during the caregiving period and after death. 4) Being behind the times: to provide palliative care in line with patients’ preferences and to feel prepared for the palliative care phase of PD, proactive palliative care planning was considered important. However, the interviewees told that this was most often not provided. Conclusion: These findings indicate that caring for a person with PD in the palliative care phase is a demanding experience for family caregivers. They experience psychological problems for many years before and after the death of the person with PD. Increasing healthcare professionals’ awareness of family and bereaved caregivers’ needs may mitigate these long-term detrimental effects. Show more

Keywords: Anticipatory bereavement, bereaved family caregivers, grief, palliative care, Parkinson’s disease, post-caregiving

DOI: 10.3233/JPD-191884

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1631-1642, 2020

Authors: Gryc, Wojciech | Roberts, Kathryn A. | Zabetian, Cyrus P. | Weintraub, Daniel | Trojanowski, John Q. | Quinn, Joseph F. | Hiller, Amie L. | Chung, Kathryn A. | Poston, Kathleen L. | Yang, Laurice | Hu, Shu-Ching | Edwards, Karen L. | Montine, Thomas J. | Cholerton, Brenna A.

Article Type: Short Communication

Abstract: Neuropsychiatric symptoms are common in Parkinson’s disease (PD). We investigated the relationship between neuropsychiatric symptoms and current and future diagnosis of PD dementia (PDD). Individuals with PD who had a study partner were enrolled (n  = 696). Study partners were administered the Neuropsychiatric Inventory or Neuropsychiatric Inventory Questionnaire at baseline. Participants were assigned a cognitive diagnosis at baseline and follow up visits. Hallucinations were significantly associated with a diagnosis of PDD cross-sectionally (p  < 0.001) and with shortened time to dementia longitudinally among initially nondemented participants (n  = 444; p  = 0.005). Screening for hallucinations may be useful for assessing risk of dementia in …participants with PD. Show more

Keywords: Behavioral symptoms, cognition, dementia, hallucinations, Parkinson’s disease

DOI: 10.3233/JPD-202116

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1643-1648, 2020

Authors: Fardell, Camilla | Torén, Kjell | Schiöler, Linus | Nissbrandt, Hans | Åberg, Maria

Article Type: Research Article

Abstract: Background: High education level and high occupational complexity have been implicated as risk factors for Parkinson’s disease (PD). Objective: The objective was to determine whether cognitive capacity, measured as IQ, in early adulthood is associated with the subsequent development of PD. Method: Data on IQ were retrieved from the Swedish Military Service Conscription Registry, comprising Swedish males who enlisted for military service in the period 1968–1993 (N = 1,319,235). After exclusion, 1,189,134 subjects in total were included in the present study. Individuals who later developed PD (N = 1,724) were identified using the Swedish National Patient Register and the Swedish …Cause of Death Register. Results: High education level was associated with PD. High IQ was associated with PD (p  < 0.0001), both when analyzed as a continuous variable and when divided into three categories. The hazard ratio for the high IQ category compared to the low IQ category was 1.35 (95% confidence interval 1.17–1.55). Strong test results on the subtests, measuring verbal, logic, visuospatial and technical abilities, were also associated with PD. In a subgroup, smoking was inversely associated with PD, as well as with IQ. Conclusions: This study identifies high IQ to be a risk factor for PD. Show more

Keywords: Parkinson’s disease, IQ, cognition, smoking, education

DOI: 10.3233/JPD-202050

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1649-1656, 2020

Authors: Glover, Aliyah | Pillai, Lakshmi | Doerhoff, Shannon | Virmani, Tuhin

Article Type: Research Article

Abstract: Background: Freezing of gait (FOG) is a debilitating feature of Parkinson’s disease (PD) for which treatments are limited. To develop neuroprotective strategies, determining whether disease progression is different in phenotypic variants of PD is essential. Objective: To determine if freezers have a faster decline in spatiotemporal gait parameters. Methods: Subjects were enrolled in a longitudinal study and assessed every 3– 6 months. Continuous gait in the levodopa ON-state was collected using a gait mat (Protokinetics). The slope of change/year in spatiotemporal gait parameters was calculated. Results: 26 freezers, 31 non-freezers, and 25 controls completed …an average of 6 visits over 28 months. Freezers had a faster decline in mean stride-length, stride-velocity, swing-%, single-support-%, and variability in single-support-% compared to non-freezers (p  < 0.05). Gait decline was not correlated with initial levodopa dose, duration of levodopa therapy, change in levodopa dose or change in Montreal Cognitive Assessment scores (p  > 0.25). Gait progression parameters were required to obtain 95% accuracy in categorizing freezers and non-freezers groups in a forward step-wise binary regression model. Change in mean stride-length, mean stride-width, and swing-% variability along with initial foot-length variability, mean swing-% and apathy scores were significant variables in the model. Conclusion: Freezers had a faster temporal decline in objectively quantified gait, and inclusion of longitudinal gait changes in a binary regression model greatly increased categorization accuracy. Levodopa dosing, cognitive decline and disease severity were not significant in our model. Early detection of this differential decline may help define freezing prone groups for testing putative treatments. Show more

Keywords: Freezing of gait, gait, falls, Parkinson’s disease, predictive modeling

DOI: 10.3233/JPD-201961

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1657-1673, 2020

Authors: Weersink, Joyce B. | Gefferie, Silvano R. | van Laar, Teus | Maurits, Natasha M. | de Jong, Bauke M.

Article Type: Research Article

Abstract: Background: The supplementary motor area (SMA) is implicated in both motor initiation and stereotypic multi-limb movements such as walking with arm swing. Gait in Parkinson’s disease exhibits starting difficulties and reduced arm swing, consistent with reduced SMA activity. Objective: We tested whether enhanced arm swing could improve Parkinson gait initiation and assessed whether increased SMA activity during preparation might facilitate such improvement. Methods: Effects of instructed arm swing on cortical activity, muscle activity and kinematics were assessed by ambulant EEG, EMG, accelerometers and video in 17 Parkinson patients and 19 controls. At baseline, all participants repeatedly …started walking after a simple auditory cue. Next, patients started walking at this cue, which now meant starting with enhanced arm swing. EEG changes over the putative SMA and leg motor cortex were assessed by event related spectral perturbation (ERSP) analysis of recordings at Fz and Cz. Results: Over the putative SMA location (Fz), natural PD gait initiation showed enhanced alpha/theta synchronization around the auditory cue, and reduced alpha/beta desynchronization during gait preparation and movement onset, compared to controls. Leg muscle activity in patients was reduced during preparation and movement onset, while the latter was delayed compared to controls. When starting with enhanced arm swing, these group differences virtually disappeared. Conclusion: Instructed arm swing improves Parkinson gait initiation. ERSP normalization around the cue indicates that the attributed information may serve as a semi-internal cue, recruiting an internalized motor program to overcome initiation difficulties. Show more

Keywords: Arm swing, Parkinson’s disease, gait initiation, supplementary motor area, ambulant electroencephalography

DOI: 10.3233/JPD-202112

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1675-1693, 2020

Authors: Ngo, Angeline B. | Smith, Kara M.

Article Type: Short Communication

Abstract: We investigated patient and clinician impressions of cognitive impairment and whether they correlated with objective measures of cognitive impairment. Cognitive categorization, neuropsychological assessment scores, and Montreal Cognitive Assessment scores were documented at baseline, 3 years, and 7 years for 388 PD patients in the Parkinson’s Progression Markers Initiative (PPMI). We found that both patient and clinician impressions of cognitive decline were significantly associated with gold-standard criteria for cognitive impairment to a similar degree. Both patient and clinician perspectives should be considered in determining cognitive status and should be followed up with diagnostic testing.

Keywords: Cognitive impairment, subjective cognitive decline, Parkinson’s disease, Parkinson’s progression markers initiative

DOI: 10.3233/JPD-202110

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1695-1698, 2020

Authors: Ruck, Laura | Unger, Marcus M. | Spiegel, Jörg | Bürmann, Jan | Dillmann, Ulrich | Faßbender, Klaus | Reith, Wolfgang | Backens, Martin | Mühl-Benninghaus, Ruben | Yilmaz, Umut

Article Type: Research Article

Abstract: Background: Altered gastric motility is a frequent non-motor symptom of Parkinson’s disease (PD). It has been hypothesized that disturbed gastric motility contributes to motor fluctuations in PD due to an erratic gastro-duodenal transport and an unpredictable absorption of drugs. Objective: We investigated whether patient-reported fluctuations are associated with parameters of gastric motility visualized by real-time magnetic resonance imaging (MRI) of the stomach. Methods: We analyzed real-time MRI-scans of the stomach after an overnight fasting period in 16 PD patients and 20 controls. MRI was performed 1) in the fasting state, 2) directly after a test meal, …and 3) 4 hours postprandially. Gastric motility indices were calculated and compared between groups. Results: MRI showed an attenuated gastric motility in PD patients compared to controls. The difference was most obvious in the early postprandial phase. Gastric motility was not associated with patient-reported motor fluctuations. Using an iron-containing capsule we were able to retrace retention of drugs in the stomach. Conclusion: The results of this study stress the importance of considering the phase of digestion when investigating gastric motility in PD. Despite theoretical considerations, we did not find robust evidence for an association between MRI parameters of gastric motility and patient-reported motor fluctuations. For future studies that aim to investigate gastric motility in PD by MRI, we suggest multiple short-time MRIs to better track the whole gastro-duodenal phase in PD. Such an approach would also allow to retrace the retention of drugs in the stomach as shown by our approach using an iron-containing capsule. Show more

Keywords: Parkinson’s disease, gastrointestinal motility, stomach, real-time magnetic resonance imaging

DOI: 10.3233/JPD-202144

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1699-1707, 2020

Authors: Di Luca, Daniel G. | Sambursky, Jacob A. | Margolesky, Jason | Cordeiro, Joacir Graciolli | Diaz, Anthony | Shpiner, Danielle S. | Moore, Henry P. | Singer, Carlos | Luca, Corneliu

Article Type: Research Article

Abstract: Background: Randomized clinical trials (RCTs) in Parkinson’s disease (PD) have historically enrolled a low number of underrepresented minorities, lessening the generalizability of therapeutic developments. Although there are racial disparities in PD, little is known regarding neuropsychiatric symptoms and other nonmotor manifestations across all races/ethnicities. Objective: To assess minority participation in PD trials evaluating the treatment of neuropsychiatric symptoms and explore underlying reasons. Methods: We systematically searched PubMed and Embase for RCTs with a primary goal of treating neuropsychiatric symptoms in PD patients from 2000-2019. The pooled prevalence and 95% confidence interval (CI) of being white and …enrolled in a clinical trial was calculated using the inverse variance method. I-square was calculated as a measure of heterogeneity and meta-regression was used to evaluate temporal trends. Results: We included 63 RCTs with a total of 7,973 patients. In pooled analysis, 11 (17.5%) RCTs reported race/ethnicity. Of studies reporting this data, 5 African American (0.2%), 16 Hispanics (0.64%), and 539 Asians (21.44%) were enrolled. The pooled prevalence of being white in clinical trials was 98% (CI 0.97–0.98, p  < 0.001), with 1,908 patients (75.8%). NIH-funded studies were most likely to report racial data when compared to non-NIH trials (p  = 0.032). Conclusion: This large pooled analysis found a small percentage of RCTs reporting race/ethnicity when evaluating treatment of neuropsychiatric symptoms in PD. There was a disproportionally high number of white patients when compared to African Americans and Hispanics. More studies are needed to investigate this discrepancy and improve rates of & minority enrollment in PD trials. Show more

Keywords: Health care disparities, meta-analysis, neuropsychiatry, Parkinson’s disease, randomized clinical trials

DOI: 10.3233/JPD-202045

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1709-1716, 2020

Authors: Del Pino, Rocio | Díez-Cirarda, Maria | Peña, Javier | Ibarretxe-Bilbao, Naroa | Ojeda, Natalia

Article Type: Research Article

Abstract: Background: The estimation of premorbid intelligence (PI) is needed for an accurate diagnosis. Objective: This study aimed to estimate the cognitive performance taking into account the PI in Parkinson’s disease (PD) compared to healthy controls (HC); and to analyze the discrepancies between the current and the predicted cognitive performance based on the PI. Method: Semantic fluency, verbal and visual memory, and executive functions were assessed in 39 PD and 162 HC. A linear regression model was used to analyze the discrepancies between the predicted cognitive performance and the current raw scores through PI variables (Word Accentuation …Test (WAT), Pseudo-Words (PW) Reading subtest from PROLEC-R, age, and years of education). ROC analyses were performed to assess their diagnostic properties. Results: Significant differences were found in the raw cognitive scores between patients and HC [semantic fluency (t  = 6.07; p  < 0.001), verbal memory (t  = 6.63; p  < 0.001), and executive functions (t  = 2.57; p  = 0.013), and in visual memory (t  = 1.97; p  = 0.055 marginally significant)]. Compared to HC, PD patients presented higher discrepancies between the predicted cognitive performance and the raw scores in semantic fluency, verbal memory, visual memory, executive functions (AUC = 0.78, 0.78; 0.64, 0.61, respectively). Conclusion: The magnitude of the discrepancies scores between the current and the predicted cognitive performance based on PI indicates the presence of cognitive decline in the specific cognitive domain in PD patients. This study underlines the usefulness of premorbid measures and variables, such as WAT, PW, age, and years of education, to more accurately estimate the cognitive performance in PD. Show more

Keywords: Neuropsychological assessment, Parkinson’s disease, premorbid intelligence, pseudo-words, WAT

DOI: 10.3233/JPD-202142

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1717-1725, 2020

Authors: Claus, Inga | Muhle, Paul | Suttrup, Judith | Labeit, Bendix | Suntrup-Krueger, Sonja | Dziewas, Rainer | Warnecke, Tobias

Article Type: Research Article

Abstract: Background: Diagnosis of pharyngeal dysphagia in patients with Parkinson’s disease is often difficult as reliable screening methods are lacking so far and clinical examination fails to adequately assess the pharyngeal phase of swallowing. Objective: To identify clinical predictors indicating the presence of pharyngeal dysphagia in patients at risk. Methods: We examined pharyngeal dysphagia in a large cohort of patients with Parkinson’s disease (n  = 200) divided in three clinical subtypes (tremor-dominant (TD), mainly bradykinetic (BK) and early postural instability and gait difficulty PIGD)) by using flexible endoscopic evaluation of swallowing. ANOVA-multivariance analysis and following t -tests as …well as binary logistic regression analysis were performed to detect group differences and to identify clinical predictors for dysphagia. Results: Statistically significant differences were found in the dysphagic group: age, male gender, disease duration, stage of the disease, Levodopa equivalent dose and higher scores on the Unified Parkinson’s disease rating scale III and II, item 7. The PIGD subtype was affected more frequently than the TD and BK subtype. In a logistic regression model higher age (>63.5 years p  < 0.05) and Levodopa equivalent dose (>475 mg, p  < 0.01) were identified to be independent predictors for the presence of pharyngeal dysphagia. Conclusion: Particularly patients with an age > 63.5 years and a daily Levodopa equivalent dose >475 mg show an increased risk for pharyngeal dysphagia. These findings may partly be influenced by presbyphagia but are likely to represent disease progression. The PIGD subtype seems to be a risk factor due to more pronounced dyscoordination of oropharyngeal muscle movements. Show more

Keywords: Parkinson’s disease, oropharyngeal dysphagia, deglutition disorders, swallowing disorders

DOI: 10.3233/JPD-202081

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1727-1735, 2020

Authors: Tang, Chris C. | Holtbernd, Florian | Ma, Yilong | Spetsieris, Phoebe | Oh, Alice | Fink, Gereon R. | Timmermann, Lars | Eggers, Carsten | Eidelberg, David

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by brain metabolic networks, specifically associated with motor and cognitive manifestations. Few studies have investigated network changes in cerebral hemispheres ipsilateral and contralateral to the clinically more affected body side. Objective: We examined hemispheric network abnormalities and their relationship to striatal dopaminergic deficits in PD patients at different stages. Methods: 45 PD patients underwent dual-tracer positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and 18 F-fluorodopa (FDOPA) in a high-resolution PET scanner. In all patients, we computed expression levels for the PD-related motor/cognition metabolic patterns (PDRP/PDCP) as well as putamen/caudate …FDOPA uptake values in both hemispheres. Resulting hemispheric measures in the PD group were compared with corresponding healthy control values and assessed across disease stages. Results: Hemispheric PDRP and PDCP expression was significantly elevated contralateral and ipsilateral to the more affected body side in patients with unilateral symptoms (H&Y 1: p  < 0.01) and in patients with bilateral limb involvement (H&Y 2-3: p  < 0.001; H&Y 4: p  < 0.003). Elevations in pattern expression were symmetrical at all disease stages. By contrast, FDOPA uptake in the caudate and putamen was reduced bilaterally (p  < 0.002), with lower values on both sides at more advanced disease stages. Hemispheric uptake was asymmetrical in both striatal regions, with lower contralateral values at all disease stages. The magnitude of hemispheric uptake asymmetry was smaller with more advanced disease, reflecting greater change ipsilaterally. Conclusion: Symmetrical network expression in PD represents bilateral functional effects unrelated to nigrostriatal dopaminergic asymmetries. Show more

Keywords: Parkinson’s disease, brain metabolic networks, PET, brain metabolism, dopaminergic function

DOI: 10.3233/JPD-202117

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1737-1749, 2020

Authors: DeKarske, Daryl | Alva, Gustavo | Aldred, Jason L. | Coate, Bruce | Cantillon, Marc | Jacobi, Lori | Nunez, Rene | Norton, James C. | Abler, Victor

Article Type: Research Article

Abstract: Background: Many patients with Parkinson’s disease (PD) experience depression. Objective: Evaluate pimavanserin treatment for depression in patients with PD. Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale–17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in …patients who received ≥1 pimavanserin dose. Results: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was –10.8 (0.63) (95% CI, –12.0 to –9.5; p  < 0.0001) with significant improvement seen at week 2 (p  < 0.0001) and for both monotherapy (week 8, –11.2 [0.99]) and adjunctive therapy (week 8,–10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n  = 7; 14.9%) and psychiatric (n  = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III. Conclusion: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD. Show more

Keywords: Parkinson’s disease, depression, dementia, pimavanserin, adjunctive therapy, monotherapy

DOI: 10.3233/JPD-202058

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1751-1761, 2020

Authors: Gaßner, Heiko | Sanders, Philipp | Dietrich, Alisa | Marxreiter, Franz | Eskofier, Bjoern M. | Winkler, Jürgen | Klucken, Jochen

Article Type: Research Article

Abstract: Background: Gait impairments in Parkinson’s disease (PD) are quantified using inertial sensors under standardized test settings in the hospital. Recent studies focused on the assessment of free-living gait in PD. However, the clinical relevance of standardized gait tests recorded at the patient’s home is unclear. Objective: To evaluate the reliability of supervised, standardized sensor-based gait outcomes at home compared to the hospital. Methods: Patients with PD (n  = 20) were rated by a trained investigator using the Unified Parkinson Disease Rating Scale (UPDRS-III). Gait tests included a standardized 4×10 m walk test and the Timed Up and Go …Test (TUG). Tests were performed in the hospital (HOSPITAL) and at patients’ home (HOME), and controlled for investigator, time of the day, and medication. Statistics included reliability analysis using Intra-Class correlations and Bland-Altman plots. Results: UPDRS-III and TUG were comparable between HOSPITAL and HOME. PD patients’ gait at HOME was slower (gait velocity Δ = –0.07±0.11 m/s, –6.1%), strides were shorter (stride length Δ = –9.2±9.4 cm; –7.3%), and shuffling of gait was more present (maximum toe-clearance Δ = –0.7±2.5 cm; –8.8%). Particularly, narrow walkways (<85 cm) resulted in a significant reduction of gait velocity at home. Reliability analysis (HOSPITAL vs. HOME) revealed excellent ICC coefficients for UPDRS-III (0.950, p  < 0.000) and gait parameters (e.g., stride length: 0.898, p  < 0.000; gait velocity: 0.914, p  < 0.000; stance time: 0.922, p  < 0.000; stride time: 0.907, p  < 0.000). Conclusion: This pilot study underlined the clinical relevance of gait parameters by showing excellent reliability for supervised, standardized gait tests at HOSPITAL and HOME, even though gait parameters were different between test conditions. Show more

Keywords: Parkinson’s disease, gait analysis, wearable sensors, telemedicine, home monitoring

DOI: 10.3233/JPD-202129

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1763-1773, 2020

Authors: Tosserams, Anouk | Nijkrake, Maarten J. | Sturkenboom, Ingrid H.W.M. | Bloem, Bastiaan R. | Nonnekes, Jorik

Article Type: Short Communication

Abstract: Compensation strategies are an essential part of managing gait impairments in people with Parkinson’s disease (PD). We conducted an online survey among 320 healthcare professionals with specific expertise in PD management, to evaluate their knowledge of compensation strategies for gait impairments in people with PD, and whether they applied these in daily practice. Only 35% of professionals was aware of all categories of compensation strategies. Importantly, just 23% actually applied all seven available categories of strategies when treating people with PD in clinical practice. We discuss the clinical implications, and provide recommendations to overcome this knowledge gap.

Keywords: Parkinson’s disease, rehabilitation, compensation strategies, healthcare, survey

DOI: 10.3233/JPD-202176

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1775-1778, 2020

Authors: Tarolli, Christopher G. | Andrzejewski, Kelly | Zimmerman, Grace A. | Bull, Michael | Goldenthal, Steven | Auinger, Peggy | O’Brien, Michael | Dorsey, E. Ray | Biglan, Kevin | Simuni, Tanya

Article Type: Research Article

Abstract: Background: There is rising interest in remote clinical trial assessments, particularly in the setting of the COVID-19 pandemic. Objective: To demonstrate the feasibility, reliability, and value of remote visits in a phase III clinical trial of individuals with Parkinson’s disease. Methods: We invited individuals with Parkinson’s disease enrolled in a phase III clinical trial (STEADY-PD III) to enroll in a sub-study of remote video-based visits. Participants completed three remote visits over one year within four weeks of an in-person visit and completed assessments performed during the remote visit. We evaluated the ability to complete scheduled assessments …remotely; agreement between remote and in-person outcome measures; and opinions of remote visits. Results: We enrolled 40 participants (mean (SD) age 64.3 (10.4), 29% women), and 38 (95%) completed all remote visits. There was excellent correlation (ICC 0.81–0.87) between remote and in-person patient-reported outcomes, and moderate correlation (ICC 0.43–0.51) between remote and in-person motor assessments. On average, remote visits took around one quarter of the time of in-person visits (54 vs 190 minutes). Nearly all participants liked remote visits, and three-quarters said they would be more likely to participate in future trials if some visits could be conducted remotely. Conclusion: Remote visits are feasible and reliable in a phase III clinical trial of individuals with early, untreated Parkinson’s disease. These visits are shorter, reduce participant burden, and enable safe conduct of research visits, which is especially important in the COVID-19 pandemic. Show more

Keywords: Clinical trial protocol, Parkinson’s disease, phase III clinical trial, technology, telemedicine

DOI: 10.3233/JPD-202163

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1779-1786, 2020

Authors: Pona-Ferreira, Joana | Ferreira, Joaquim J.

Article Type: Letter

DOI: 10.3233/JPD-202226

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1787-1788, 2020

Authors: Cao, Zichun | Luo, Zhehui | Huang, Xuemei | Pinto, Jayant M. | Simonsick, Eleanor M. | Shiroma, Eric J. | Chen, Honglei

Article Type: Research Article

Abstract: Background: Poor olfaction is a prodromal symptom of Parkinson’s disease (PD); however, self-reported sense of smell is often dismissed as unreliable. Objective: To assess self-reported and objectively assessed sense of smell, independently and jointly, in relation to future risk for PD. Methods: We conducted a prospective analysis using data from 2,424 participants, ages 71–82 at baseline, from the Health, Aging, and Body Composition study. Exposures were self-reported poor sense of smell or taste and the objectively measured 12-item Brief Smell Identification Test score. The outcome was incident PD, analyzed using Cox proportional hazard models adjusted for …age, sex, race, and cognitive function. Results: After approximately 10 years of follow-up, both self-reported and objectively tested poor sense of smell were independently associated with a higher risk of developing PD: the hazard ratios (95% confidence interval) were 2.8 (1.3, 5.9) and 4.0 (2.1, 7.5), respectively. When analyzed jointly, compared with participants who reported and tested normal, the hazard ratio was 2.2 (1.0, 4.6) for those reported poor sense of smell but tested normal, 3.6 (1.9, 6.9) for reported normal but tested poor, and 7.8 (3.2, 19.4) for both reported and tested poor. We did not find significant interactions between self-reported and objectively tested sense of smell in predicting PD risk. Conclusion: This study provides preliminary evidence that self-reported poor sense of smell or taste should not be simply dismissed as useless in predicting risk of PD. Future studies should confirm our finding and evaluate whether structured questionnaires may further improve the predictability. Show more

Keywords: Parkinson’s disease, self-report, olfaction, sense of smell

DOI: 10.3233/JPD-202164

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1789-1795, 2020

Authors: Diederich, Nico J. | Sauvageot, Nicolas | Pieri, Vannina | Hipp, Géraldine | Vaillant, Michel

Article Type: Research Article

Abstract: Background: Non-motor symptoms (NMS) of various anatomical origins are seen in early stage idiopathic Parkinson’s disease (IPD). Objective: To analyse when and how NMS are linked together at this stage of the disease. Methods: Prospective study recruiting 64 IPD patients with ≤3 years of disease duration and 71 age-matched healthy controls (HC). NMS were clustered in 7 non-motor domains (NMD): general cognition, executive function, visuospatial function, autonomic function, olfaction, mood, and sleep. Correlation coefficients ≥|0.3| were considered as significant. Bootstrapped correlation coefficients between the scores were generated in both groups. Fourteen IPD patients and 19 HC …were available for a follow-up study two years later. Results: The mean age of both groups was similar. 58% of IPD patients and 37% of HC were male (p  = 0.01). At baseline IPD patients performed less well than HC on all NMD (p value between 0.0001 and 0.02). Out of 91 possible correlations between NMD, 21 were significant in IPD patients and 14 in HC at the level of ≥|0.3|. The mean correlation level was higher in IPD patients than in HC, as evidenced by the higher box plot of correlation coefficients. Visuospatial scores at baseline were predictive of the motor deterioration at the follow-up exam. Conclusion: At early IPD stage various NMS are linked together, although not connected by anatomical networks. Such a clinical NMD connectome suggests almost synchronous disease initiation at different sites as also supported by fMRI findings. Alternatively, there may be compensation-driven interconnectivity of NMD. Show more

Keywords: Parkinson’s disease, non-motor symptoms, connectome, compensation

DOI: 10.3233/JPD-202102

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1797-1806, 2020

Authors: Fernandez-Baizan, Cristina | Paula Fernandez Garcia, M. | Diaz-Caceres, Elena | Menendez-Gonzalez, Manuel | Arias, Jorge L. | Mendez, Marta

Article Type: Research Article

Abstract: Background: Visuospatial skills are impaired in Parkinson’s disease (PD). Other related skills exist, such as spatial orientation have been poorly studied. The egocentric (based on internal cues) and allocentric frameworks (based on external cues) are used in daily spatial orientation. Depending on PD onset, the allocentric framework may have a higher level of impairment in tremor-dominant and the egocentric one in akinetic-rigid. Objective: To evaluate spatial orientation and visuospatial functions in PD patients and controls, and to assess whether their performance is related to disease duration and the PD subtype (tremor-dominant and akinetic-rigid). Methods: We evaluated …egocentric and allocentric spatial orientation (Egocentric and Allocentric Spatial Memory Tasks) and visuospatial abilities, span and working memory in 59 PD patients and 51 healthy controls. Results: Visuospatial skills, visuospatial span, and egocentric and allocentric orientation are affected in PD. Visuospatial skills and allocentric orientation undergo deterioration during the first 5 years of the disease progression, while egocentric orientation and visuospatial span do so at later stages (9–11 years). The akinetic-rigid subtype presents worse results in all the spatial abilities that were measured when compared to controls, and worse scores in visuospatial working memory, visuospatial abilities and allocentric orientation when compared to the tremor-dominant group. The tremor-dominant group performed worse than controls in egocentric and allocentric orientation. Conclusion: PD patients show deficits in their visuospatial abilities and in their egocentric and allocentric spatial orientation compared to controls, specifically in akinetic-rigid PD. Only spatial orientation are affected in tremor-dominant PD patients. Allocentric orientation is affected earlier in the progression of the disease. Show more

Keywords: Parkinson’s disease, spatial frameworks, spatial orientation, spatial learning

DOI: 10.3233/JPD-202122

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1807-1816, 2020

Authors: Ghosh, Pritha | Imbriani, Paola | Caputi, Nicoletta | Natoli, Silvia | Schirinzi, Tommaso | Di Lazzaro, Giulia | Covington, Lindsey | Sparks, Andrew D. | Salnikova, Yekaterina | Rukavina, Katarina | Ray Chaudhuri, K. | Pisani, Antonio

Article Type: Research Article

Abstract: Background: Pain is a disabling and often underestimated non-motor symptom (NMS) detrimentally affecting the quality of life of patients with Parkinson’s disease (PD). Objective: Here, we conducted a cross-sectional, observational international study on 167 patients with idiopathic PD in order to analyze the potential relationship between pain and other NMS. Methods: Subjects were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, Hoehn and Yahr (H&Y) stage, King’s Parkinson’s Disease Pain Scale (KPPS), Brief Pain Inventory (BPI), Non-Motor Symptoms Scale (NMSS), and Beck Depression Inventory (BDI). Spearman’s rank correlation coefficient, multiple regression and multiple …index-based clustering algorithms were used for data analysis. Results: The prevalence of pain was 88.6%, was not correlated with age, motor severity (UPDRS part III) or disease duration, whereas a weak correlation with female gender and H&Y stage >2.5 was found. Multiple NMS correlated significantly with pain. Specifically, sleep disturbance had the strongest correlation with pain, followed by depression, gastrointestinal and cardiovascular disturbances. Further analyses showed that sleep and cardiovascular disturbance were independently associated with pain, and that these symptoms clustered together in a subset of PD patients. The relationship between pain, sleep and dysautonomia persisted independently from dopamine replacement therapy. Conclusion: Our study suggests that sleep disruption and cardiovascular disturbance are associated with pain in PD, and possibly identifies a specific subtype within PD patients with pain. Our data also indicate that sleep disruption, pain and dysautonomia may have a common pathophysiology, possibly involving non-dopaminergic pathways. Show more

Keywords: Neurodegeneration, noradrenergic pathway, pain, parkinsonism, serotonergic pathway

DOI: 10.3233/JPD-202088

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1817-1825, 2020

Authors: Dominey, Thea | Kehagia, Angie A. | Gorst, Terry | Pearson, Emma | Murphy, Fiona | King, Emma | Carroll, Camille

Article Type: Research Article

Abstract: In an effort to provide timely clinical input for people with Parkinson’s disease (PD) in the face of increasing demand and resource limitation in our UK based service, we introduced remote management in place of clinic appointment, including the use of the Parkinson’s KinetiGraph (PKG™), a wrist-worn device that provides a continuous measure of movement. We evaluated our reporting methods and findings, the nature of unmet need we identified, our treatment recommendations and the degree of their implementation in our patients whose feedback guided our service developments. Our evaluation highlighted opportunities and challenges associated with incorporating digital data into care …traditionally delivered via in-person contact. Show more

Keywords: Parkinson’s disease, PKG, remote sensing technology, wearable devices

DOI: 10.3233/JPD-202101

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1827-1832, 2020

Authors: Tamás, Gertrúd | Fabbri, Margherita | Falup-Pecurariu, Cristian | Teodoro, Tiago | Kurtis, Mónica M. | Aliyev, Rahim | Bonello, Michael | Brozova, Hana | Coelho, Miguel Soares | Contarino, Maria Fiorella | Corvol, Jean-Christophe | Dietrichs, Espen | Ben Djebara, Mouna | Elmgreen, Søren Bruno | Groppa, Sergiu | Kadastik-Eerme, Liis | Khatiashvili, Irine | Kostić, Vladimir | Krismer, Florian | Hassan Mansour, Alia | Odin, Per | Gavriliuc, Olga | Olszewska, Diana Angelika | Relja, Maja | Scheperjans, Filip | Skorvanek, Matej | Smilowska, Katarzyna | Taba, Pille | Tavadyan, Zaruhi | Valante, Ramona | Vujovic, Balsa | Waldvogel, Daniel | Yalcin-Cakmakli, Gul | Chitnis, Shilpa | Ferreira, Joaquim J.

Article Type: Research Article

Abstract: Background: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa. Objective: To survey the accessible MD clinical training in these regions. Methods: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants …also shared their suggestions and needs. Results: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology. Conclusion: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries. Show more

Keywords: Movement disorders, Parkinson’s disease, education, curriculum, neurology

DOI: 10.3233/JPD-202000

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1833-1843, 2020