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