Journal of Parkinson's Disease - Volume 12, issue 1

Authors: Brolin, Kajsa | Bandres-Ciga, Sara | Blauwendraat, Cornelis | Widner, Håkan | Odin, Per | Hansson, Oskar | Puschmann, Andreas | Swanberg, Maria

Article Type: Research Article

Abstract: Background: Risk factors for Parkinson’s disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. Objective: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. Methods: PD patients (n  = 929) and matched population-based controls (n  = 935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures …was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. Results: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA . In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445). Conclusion: This work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors for PD in the Swedish population. Show more

Keywords: Parkinson’s disease, Sweden, case-control studies, risk factors, genome-wide association study, haplotypes

DOI: 10.3233/JPD-212818

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 153-171, 2022

Authors: Chiu, Shu-Fen | Wu, Yih-Ru | Tsay, Pei-Kwei | Chiu, Yi-Chen

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD), a degenerative disease with irreversible motor dysfunction, impacts patients’ quality of life (QoL). Spirituality can provide a sense of hope and meaning when individuals are faced with adverse life events, such as a diagnosis of PD. However, few studies have examined the relationship between spiritual well-being and QoL for persons with PD. Objective: To explore the relationships between the disease characteristics, spirituality and QoL for persons with PD, and verify the mediating effects of spirituality on the relationship. Methods: This cross-sectional study recruited patients with PD (n  = 110) by convenience sampling from …a neurological clinic in northern Taiwan. Variables were measured using the Spirituality Index of Well-Being Chinese version (SIWB-C) and the 39-item Parkinson’s disease Quality of Life Questionnaire Chinese version (PDQ-39-C) self-report questionnaires. Descriptive analysis and linear hierarchical regression were conducted to examine the studied variables and explore the mediating effect of spiritual wellbeing. Results: Those whose scores were significantly better in PDQ-39 were younger, employed, with shorter disease duration and less severe condition with better functioning on their early stages and lower LEDD; additionally, those who had better quality of life also experienced better spiritual wellbeing than the counterparts. The regression model demonstrated spiritual self-efficacy had mediating effects between disease characteristics and QoL, explaining 69.8%of the variance (adjusted R 2  = 65.3%). Conclusion: The results can be the references for future strategies and interventions, focusing on increasing spiritual self-efficacy and reducing the impact of disease severity to improve QoL for persons with PD. Show more

Keywords: Parkinson’s disease, spiritual well-being, self-efficacy, quality of life

DOI: 10.3233/JPD-212764

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 173-184, 2022

Authors: Chuang, Yu-Han | Tan, Chun-Hsiang | Su, Hui-Chen | Chien, Chung-Yao | Sung, Pi-Shan | Lee, Tsung-Lin | Yu, Rwei-Ling

Article Type: Research Article

Abstract: Background: Hypomimia is a clinical feature of Parkinson’s disease (PD). Based on the embodied simulation theory, the impairment of facial mimicry may worsen facial emotion recognition; however, the empirical results are inconclusive. Objective: We aimed to explore the worsening of emotion recognition by hypomimia. We further explored the relationship between the hypomimia, emotion recognition, and social functioning. Methods: A total of 114 participants were recruited. The patients with PD and normal controls (NCs) were matched for demographic characteristics. All the participants completed the Mini-Mental State Examination and the Chinese Multi-modalities Emotion Recognition Test. In addition to …the above tests, the patients were assessed with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Social Functioning Scale (PDSFS). Results: Patients with PD with hypomimia had worse recognition of disgust than NCs (p  = 0.018). The severity of hypomimia was predictive of the recognition of disgust (β= –0.275, p  = 0.028). Facial emotion recognition was predictive of the PDSFS score of PD patients (β= 0.433, p  = 0.001). We also found that recognizing disgust could mediate the relationship between hypomimia and the PDSFS score (β= 0.264, p  = 0.045). Conclusion: Patients with hypomimia had the worst disgust facial recognition. Hypomimia may affect the social function of PD patients, which is related to recognizing the expression of disgust. Emotion recognition training may improve the social function of patients with PD. Show more

Keywords: Parkinson’s disease, hypomimia, embodied simulation theory, emotion recognition, social function

DOI: 10.3233/JPD-212830

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 185-197, 2022

Authors: Sinai, Alon | Nassar, Maria | Sprecher, Elliot | Constantinescu, Marius | Zaaroor, Menashe | Schlesinger, Ilana

Article Type: Research Article

Abstract: Background: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief. Objective: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson’s disease (TDPD) patients. Methods: We report outcome of FUS thalamotomy in TDPD patients with 1–5 years of follow-up. Outcomes: tremor reduction assessed with Clinical Rating Scale for Tremor (CRST) and Unified Parkinson’s Disease Rating Scale (UPDRS part III) overall and in the treated hemibody and safety. Results: Twenty-six TDPD patients completed 1–5 years of follow-up (median follow-up 36 months, range 12–60 months). Median age …was 60 years (range 46–79), with median disease duration of 6 years (range 2–16). Immediately, treatment resulted in 100%improvement in tremor in the treated arm in 23 patients and 90%improvement in 3 patients. In 15 patients with leg tremor, 2 patients with chin tremor and 1 patient with head tremor, tremor was significantly improved. Up to 5 years, median CRST score, median UPDRS score, overall and in treated hemibody, decreased significantly as compared with baseline (p  < 0.0001). In 2 patients tremor returned completely and in 8 patients there was partial return of tremor. Adverse events were mild and resolved within 3 months. At baseline 4 patients were not receiving any medication vs. 3 at last follow-up and 15 were not taking levodopa vs.9 at last follow-up. Conclusion: Unilateral FUS VIM-thalamotomy in TDPD patients was effective and safe and provided long-term tremor relief in most patients. FUS thalamotomy for tremor may delay initiation of levodopa treatment. Show more

Keywords: Parkinson’s disease, treatment, tremor, ultrasound, surgery

DOI: 10.3233/JPD-212810

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 199-206, 2022

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

Article Type: Research Article

Abstract: Background: Palliative care for persons with Parkinson’s disease (PD) is developing. However, little is known about the experiences of patients with PD in the palliative phase and of their family caregivers. Objective: To explore needs of patients with PD in the palliative phase and of their family caregivers. Methods: A mixed methods case study design. Health care professionals included patients for whom the answer on the question “Would you be surprised if this patient died in the next 12 months?” was negative. At baseline, and after six and twelve months, we conducted semi-structured interviews with patients …and caregivers. Participants completed questionnaires on quality of life, disease burden, caregiver burden, grief, and positive aspects of caregiving. We analyzed quantitative data using descriptive statistics, while we used thematic analysis for qualitative data. Results: Ten patients and eight family caregivers participated, of whom five patients died during the study period. While the quantitative data reflected a moderate disease burden, the qualitative findings indicated a higher disease burden. Longitudinal results showed small differences and changes in time. Patients reported a diverse range of symptoms, such as fatigue, immobility, cognitive changes, and hallucinations, which had a tremendous impact on their lives. Nevertheless, they rated their overall quality of life as moderate to positive. Family caregivers gradually learned to cope with difficult situations such delirium, fluctuations in functioning and hallucinations. They had great expertise in caring for the person with PD but did not automatically share this with health care professionals. Patients sensed a lack of time to discuss their complex needs with clinicians. Furthermore, palliative care was rarely discussed, and none of these patients had been referred to specialist palliative care services. Conclusion: Patients with PD experienced many difficulties in daily living. Patients seems to adapt to living with PD as they rated their quality of life as moderate to positive. Family caregivers became experts in the care for their loved one, but often learned on their own. An early implementation of the palliative care approach can be beneficial in addressing the needs of patients with PD and their family caregivers. Show more

Keywords: Parkinson’s disease, case study, palliative care, family caregivers, patients, mixed methods

DOI: 10.3233/JPD-212742

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 207-219, 2022

Authors: McDaniels, Bradley | Lee, Chun-Lung | Bishop, Malachy

Article Type: Research Article

Abstract: Background: Positive personality resources have demonstrated the ability to positively impact health outcomes. Objective: To examine the psychometric properties of the original Psychological Capital Questionnaire (PCQ-24) in patients with Parkinson’s disease (PD). Methods: A sample of 114 individuals with PD completed the PCQ-24, and via a latent factor modeling framework exploratory and confirmatory factor analyses were conducted to evaluate the psychometric properties in people with PD. Results: Exploratory factor analysis (EFA) revealed that both the efficacy and hope scales were reliable (Cronbach’s alpha = 0.87 and 0.86, respectively) and had statistically acceptable validity with strong factor …loadings all above the practical threshold of 0.60. The resilience and optimism scales were also reliable (Cronbach’s alpha = 0.78 and 0.73, respectively) but had only moderately acceptable validity in part due to three reverse-scored items (i.e., No. 13, 20, & 23) with weak factor loadings of 0.26, 0.46, and 0.50, respectively. After excluding these at-risk items, the overall factor loadings for resilience and optimism were significantly improved at the acceptable above 0.60. The CFA results confirm a statistically acceptable model fit for the modified version (only 21-items) of the PCQ in the PD sample. Conclusion: Both EFA and CFA analyses provide statistical evidence supporting the modified PCQ version and demonstrate better test validity and reliability for the PD population. The refined PCQ form is both effectively shorter and psychometrically superior to the original and has promise in investigating health outcomes in people with PD. Show more

Keywords: Factor analysis, latent factor modeling, Parkinson’s disease, positive psychological capital, positive psychology, quality of life

DOI: 10.3233/JPD-212772

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 221-228, 2022

Authors: Rémillard-Pelchat, David | Rahayel, Shady | Gaubert, Malo | Postuma, Ronald B. | Montplaisir, Jacques | Pelletier, Amélie | Monchi, Oury | Brambati, Simona Maria | Carrier, Julie | Gagnon, Jean-François

Article Type: Research Article

Abstract: Background: Rapid-eye-movement sleep behavior disorder (RBD) is a major risk factor for Parkinson’s disease and dementia with Lewy bodies. More than a third of RBD patients have mild cognitive impairment (MCI), but their specific structural brain alterations remain poorly understood. Objective: This study aimed to investigate the local deformation and volume of gray and white matter tissue underlying MCI in RBD. Methods: Fifty-two idiopathic RBD patients, including 17 with MCI (33%), underwent polysomnography, neuropsychological, neurological, and magnetic resonance imaging assessments. MCI diagnosis was based on a subjective complaint, cognitive impairment on the neuropsychological battery, and preserved …daily functioning. Forty-one controls were also included. Deformation-based morphometry (DBM), voxel-based morphometry (VBM), and regional volume analyses of the corpus callosum and cholinergic basal forebrain were performed. Multiple regression models were also computed using anatomical, cognitive (composite z scores), and motor parameters. Results: Globally, patients with MCI displayed a widespread pattern of local deformation and volume atrophy in the cortical (bilateral insula, cingulate cortex, precuneus, frontal, temporal and occipital regions, right angular gyrus, and mid-posterior segment of the corpus callosum) and subcortical (brainstem, corona radiata, basal ganglia, thalamus, amygdala, and right hippocampus) regions compared to patients without MCI (DBM) or controls (DBM and VBM). Moreover, brain deformation (DBM) in patients were associated with lower performance in attention and executive functions, visuospatial abilities, and higher motor symptoms severity. Conclusion: The present study identified novel brain structural alterations in RBD patients with MCI which correlated with poorer cognitive performance. These results are consistent with those reported in patients with synucleinopathies-related cognitive impairment. Show more

Keywords: REM sleep behavior disorder, mild cognitive impairment, Parkinson’s disease/parkinsonism, dementia with Lewy bodies, magnetic resonance imaging

DOI: 10.3233/JPD-212691

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 229-241, 2022

Authors: Sosnik, Ronen | Danziger-Schragenheim, Shani | Possti, Daniel | Fahoum, Firas | Giladi, Nir | Hausdorff, Jeffrey M. | Mirelman, Anat | Maidan, Inbal

Article Type: Research Article

Abstract: Background: The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson’s disease (PD) patients for whom such changes may be even more enhanced. Objective: In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults. Methods: 30 PD patients, 30 older adults, and 11 young adults performed …a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity. Results: The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F  = 5.619, p  = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p  = 0.013). In addition, P300 latency was significantly longer in PD patients (p  < 0.001) and older adults (p  = 0.032) during walking compared to sitting and during ‘NoGo’ trials compared with ‘Go’ trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated. Conclusion: The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels. Show more

Keywords: Parkinson’s disease, inhibitory control, EEG, dual task, gait

DOI: 10.3233/JPD-212776

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 243-256, 2022

Authors: Zolfaghari, Sheida | Yao, Chun W. | Wolfson, Christina | Pelletier, Amelie | Postuma, Ronald B.

Article Type: Research Article

Abstract: Background: Earlier detection of parkinsonism, specifically during its prodromal stage, may be key to preventing its progression. Previous studies have produced contradictory results on the association between sleep symptoms and prodromal parkinsonism. Objective: We conducted a prospective study within the Canadian Longitudinal Study on Aging (CLSA) to determine whether self-reported symptoms of insomnia, somnolence, apnea, and restless legs syndrome predate the diagnosis of parkinsonism after three years of follow-up. Methods: At baseline, amongst other information, participants completed a questionnaire for difficulty initiating or maintaining sleep, daytime somnolence, snoring or stopping breathing during sleep, and symptoms of …restless legs syndrome. After 3 years of follow-up, baseline responses from participants who self-reported a new diagnosis of parkinsonism (cases) were compared to those who did not (controls). For each case, 10 controls were individually matched by age, sex, education, BMI, caffeine, smoking, and alcohol. Binary unconditional logistic regression models were used to estimate the association between sleep symptoms and new-onset parkinsonism, adjusting for age, sex, education, BMI, smoking, alcohol, and caffeine. Results: We identified 58 incident-parkinsonism cases and 580 matched controls (65.5%male, mean age = 69.60, SD = 8.0). Baseline symptoms of sleep-onset insomnia (12.1%vs. 13.0%, Adjusted OR[95%CI] = 0.87[0.32,2.33]), sleep-maintenance insomnia (24.1%vs. 20.2%, AOR = 1.01[0.46,2.20]), daytime somnolence (8.6%vs. 7.4%, AOR = 1.11[0.37,3.39]), obstructive sleep apnea (27.3%vs. 26.2%, AOR = 0.84[0.40,1.79]), and restless leg syndrome (20.6%vs. 9.9%, AOR = 1.34[0.42,4.25]) were similar among those who developed parkinsonism and those who did not. Conclusion: Symptoms of insomnia, somnolence, apnea, and restless legs did not predate a new diagnosis of parkinsonism over 3 years. Show more

Keywords: Parkinsonism, insomnia, daytime somnolence, obstructive sleep apnea, restless leg syndrome, CLSA

DOI: 10.3233/JPD-212796

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 257-266, 2022

Authors: Domenighetti, Cloé | Sugier, Pierre-Emmanuel | Sreelatha, Ashwin Ashok Kumar | Schulte, Claudia | Grover, Sandeep | Mohamed, Océane | Portugal, Berta | May, Patrick | Bobbili, Dheeraj R. | Radivojkov-Blagojevic, Milena | Lichtner, Peter | Singleton, Andrew B. | Hernandez, Dena G. | Edsall, Connor | Mellick, George D. | Zimprich, Alexander | Pirker, Walter | Rogaeva, Ekaterina | Lang, Anthony E. | Koks, Sulev | Taba, Pille | Lesage, Suzanne | Brice, Alexis | Corvol, Jean-Christophe | Chartier-Harlin, Marie-Christine | Mutez, Eugénie | Brockmann, Kathrin | Deutschländer, Angela B. | Hadjigeorgiou, Georges M. | Dardiotis, Efthimos | Stefanis, Leonidas | Simitsi, Athina Maria | Valente, Enza Maria | Petrucci, Simona | Duga, Stefano | Straniero, Letizia | Zecchinelli, Anna | Pezzoli, Gianni | Brighina, Laura | Ferrarese, Carlo | Annesi, Grazia | Quattrone, Andrea | Gagliardi, Monica | Matsuo, Hirotaka | Kawamura, Yusuke | Hattori, Nobutaka | Nishioka, Kenya | Chung, Sun Ju | Kim, Yun Joong | Kolber, Pierre | van de Warrenburg, Bart PC | Bloem, Bastiaan R. | Aasly, Jan | Toft, Mathias | Pihlstrøm, Lasse | Guedes, Leonor Correia | Ferreira, Joaquim J. | Bardien, Soraya | Carr, Jonathan | Tolosa, Eduardo | Ezquerra, Mario | Pastor, Pau | Diez-Fairen, Monica | Wirdefeldt, Karin | Pedersen, Nancy L. | Ran, Caroline | Belin, Andrea C. | Puschmann, Andreas | Hellberg, Clara | Clarke, Carl E. | Morrison, Karen E. | Tan, Manuela | Krainc, Dimitri | Burbulla, Lena F. | Farrer, Matt J. | Krüger, Rejko | Gasser, Thomas | Sharma, Manu | Elbaz, Alexis | on behalf of the Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium

Article Type: Research Article

Abstract: Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used …the inverse-variance weighted method to compute odds ratios (ORIVW ) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p  = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p  = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power. Show more

Keywords: Smoking, alcohol, coffee, Parkinson’s disease, Mendelian randomisation

DOI: 10.3233/JPD-212851

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 267-282, 2022