Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD. METHODS: In a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression. DISCUSSION: MIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.

Experiences of Living With the Nonmotor Symptoms of Parkinson's Disease: A Photovoice Study.

BACKGROUND: Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these remain poorly understood with suboptimal clinical management. These unmet needs are an important determinant of health-related quality of life (QoL) in PD. OBJECTIVE: The aim of this study was to gain insights into the experience of living with the NMS of PD in real-time using participatory action methodology. METHOD: Using the photovoice method, 14 people with PD took photographs to document their experiences of living with the NMS of PD. They composed corresponding written narratives to capture the impact of NMS on their daily activities and QoL. In total, 152 photographs and corresponding narratives were analysed using thematic analysis with an inductive approach. RESULTS: Four interrelated themes were identified. Emotional well-being and sense of self encompassed a process of adjustment to living with PD. Engaging in valued activities, adopting a positive mindset and utilising coping strategies were thought to enhance confidence and self-esteem. Social support and societal awareness highlighted the importance of supportive relationships and socialising to aid participation and avoid isolation. Barriers to social engagement included the unpredictability of NMS and nonvisible NMS being neglected or misunderstood. CONCLUSION: Findings demonstrated the far-reaching impact of nonmotor aspects of PD on emotional, occupational and social dimensions. These needs could be addressed through person-centred and comprehensive approaches to care. PATIENT OR PUBLIC CONTRIBUTION: This study utilised a participatory research approach allowing participants to choose the subjects that mattered to them and how to present their results. Additionally, a group workshop was held with people with PD, their family members and healthcare professionals to guide theme development.

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. METHODS: People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. RESULTS: Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. DISCUSSION: Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Modulation of response times in early-stage Parkinson's disease during emotional processing of embodied and non-embodied stimuli.

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson's disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

Exploring the lived experiences of individuals with Parkinson's disease and their relatives: insights into care provision experiences, disease management support, self-management strategies, and future needs in Germany (qualitative study).

BACKGROUND: Parkinson's disease (PD) significantly impacts the health-related quality of life of affected individuals and their relatives. In order to support the affected individuals and their families in coping with PD, it is essential to offer comprehensive information about their experiences. A comprehensive understanding of their lived experiences with the disease, the healthcare system, applied self-management strategies and their needs is considered crucial for developing a PD support program. Therefore, we aimed to explore the lived experiences and support needs of individuals with PD and their relatives in Germany. METHODS: This non-interventional, qualitative study conducted an explorative status quo and needs assessment. It generated knowledge through semi-structured focus groups and interviews with individuals with PD at various disease stages and their relatives. The interviews were digitally recorded, transcribed verbatim, and analysed using content analysis. RESULTS: Fifty-two individuals with PD and 29 relatives participated in eight focus groups and 13 paired and 13 individual interviews. Four themes with corresponding subthemes emerged: (1) experiences, revealing individuals' experiences around their diagnosis and with disease-specific care provision; (2) management support offers, clarifying who provides support and the type of support offered; (3) self-management, including comprehensibility, meaningfulness and manageability; and (4) future needs, differentiating between deficits and needs. Most participants expressed a sense of abandonment when obtaining self-management strategies and mastering their lives with PD, often referred to as 'life 2.0'. They identified the lack of structured and adequate provision of information, system orientation and social awareness. CONCLUSIONS: In Germany, there is an urgent need for a comprehensive PD care program that addresses the needs of individuals with PD and their relatives from the start of their care trajectory. It could assist individuals in gaining a comprehensive understanding of the disease, obtaining self-management strategies, building a support network, and becoming experts in self-managing their disease. Moreover, it may positively influence their care trajectory and reduce burdens, such as overburdening, fear of progression, and health anxiety. TRIAL REGISTRATION: German Clinical Studies Register ( https://www.drks.de/DRKS00030090 , No. DRKS00030090, Date of registration: 15.12.2022).

The Parkinson's Puzzle Box.

INTRODUCTION: Women and those with younger onset Parkinson's Disease (YOPD) are typically diagnosed later and face unique situations and challenges. This essay aims to raise awareness of the difficulties in diagnosing YOPD and the need for a personalised approach to care for women with YOPD. METHODS: Two professional women with YOPD (academic physiotherapist and practicing dentist) and a female neurologist (clinician academic) came together to write a narrative essay on their personal experience and perspectives in relation to women and YOPD. RESULTS: The essay outlines how the experience of diagnosis is likened to a complex puzzle box with many interlocking components that are hidden and difficult to solve. The concerns of the women about their identity, work, family and the future, with most supports targeting those that are older and retired are outlined. CONCLUSION: It is concluded that YOPD is a complex puzzle to solve, but can be done by understanding all the intricate interlocking components of the puzzle and combined with greater awareness could lead to earlier diagnosis and the delivery of successful person-centred care. PATIENT OR PUBLIC CONTRIBUTION: People with lived experience were involved in the essay conception and writing.

Group-based exercise for Parkinson's: a qualitative study of participants and partners' perceptions of an exercise class delivered through a community-university collaboration.

BACKGROUND: Community-based exercise programmes (CBEPs) offer a practical and viable approach to providing people with Parkinson's disease (PwP) the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study explores the perceptions of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership. METHODS: Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4). RESULTS: Thematic analysis of the data identified that a range of physical, psychological and social factors were perceived to influence engagement: (1) actively taking control, (2) exercise is medicine for the mind and body, and (3) a community working together to promote exercise for parkinson's. Participants and partners felt that the support from the group, including the instructors and student volunteers, empowered and supported PwP to proactively self-manage their health, enjoy exercise in an inclusive group setting, and develop strong social connections with others in the local Parkinson's community. Support to exercise from healthcare professionals was identified as both an enabler and barrier to participation. CONCLUSIONS: This study underscores the significance of a community-university partnership as a complementary therapeutic approach for PwP. It also provides critical reflections on its sustainability, including implications for how exercise is considered as medicine for PwP. Additionally, it offers practical recommendations to galvanise community participation and provide inclusive and viable exercise opportunities for PwP.

Telephone-based application of the Activities of Daily Living Questionnaire in patients with Parkinson's disease.

BACKGROUND: The Activities of Daily Living Questionnaire (ADLQ) focuses on assessing the ability to perform activities of daily living (ADLs) based on the self-perception of individuals with Parkinson's disease (PD). A Brazilian Portuguese version of the questionnaire is available (ADLQ-Brazil), and further investigation is needed to fully assess its measurement properties. OBJECTIVE: To investigate construct and concurrent validity of the telephone-based administration of the ADLQ-Brazil with community individuals with PD. METHODS: There were 50 adults with PD (mean age: 68 ± 9.5 years) invited to answer the ADLQ-Brazil on two randomized occasions, face-to-face and by telephone, 7 to 10 days apart. Clinical-based measures including the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale, Timed Up and Go Test, Nine Hole Peg Test, Mini-Balance Evaluation Systems Test, Apathy Scale, Beck Depression Inventory, Modified Fatigue Impact Scale, and Parkinson Disease Quality of Life Questionnaire were applied during the first session, to establish construct validity. RESULTS: The total scores on the ADLQ-Brazil were significantly associated with the clinical-based measures, thus providing evidence of construct validity. No significant differences were observed between the mean scores obtained with the face-to-face and telephone-based administration of the questionnaire (95%CI = 0.997). A high level of agreement was found in the total scores obtained between both applications of the ADLQ-Brazil (95%CI = 0.994-0.998), and most of the individual items had, on average, moderate agreement. CONCLUSION: The findings provide psychometric support for the ADLQ-Brazil as a telephone interview to assess the performance of ADLs in individuals with PD.

ANTECEDENTES: O Questionário de Atividades da Vida Diária (Activities of Daily Living Questionnaire, ADLQ, em inglês) tem como foco avaliar a capacidade de realizar atividades da vida diária (AVDs) com base na autopercepção de indivíduos com doença de Parkinson (DP). Uma versão do questionário em português do Brasil está disponível (ADLQ-Brasil), sendo necessárias mais investigações para avaliar suas propriedades de medidas. OBJETIVO: Investigar as validades de construto e concorrente da aplicação por telefone do ADLQ-Brasil com indivíduos da comunidade com DP. MéTODOS: Foram 50 adultos com DP (média de idade: 68 ± 9,5 anos) convidados a responder o ADLQ-Brasil em duas ocasiões aleatórias, presencialmente e por telefone, com intervalo de 7 a 10 dias. Instrumentos clínicos incluindo a Escala Unificada de Avaliação da Doença de Parkinson, o teste Timed Up and Go, o teste Nine Hole Peg, a versão reduzida do teste de equilíbrio Mini-Balance Evaluation Systems, a Escala de Apatia, o Inventário de Depressão de Beck, a Escala de Impacto de Fadiga Modificada e o Questionário de Qualidade de Vida na Doença de Parkinson foram aplicados na primeira sessão para estabelecer a validade de construto. RESULTADOS: Os escores totais do ADLQ-Brasil foram significativamente associados às medidas clínicas, fornecendo, assim, evidências de validade de construto. Não foram observadas diferenças significativas entre as pontuações médias obtidas entre a aplicação presencial e por telefone do questionário (IC95% = 0,997). Foi encontrado alto nível de concordância entre os escores totais do ADLQ-Brasil obtidos nas duas aplicações (IC95% = 0,994­0,998) e a maioria dos itens individuais apresentou, em média, concordância moderada. CONCLUSãO: Os achados fornecem suporte psicométrico para o ADLQ-Brasil como entrevista telefônica para avaliação do desempenho de AVDs em indivíduos com DP.

Hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice.

Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.

Exploring the experiences, priorities and preferences of people living with Parkinson's on exercise and physical activity promotion in the UK.

BACKGROUND: People with Parkinson's (PwP) want access to timely, relevant, and specific exercise and physical activity (PA) information to enable them to manage their symptoms and maintain wellbeing and quality of life. Research that promotes exercise in this population group is limited. Little is also known about the clinical practice around PA promotion in this population, especially around the time of diagnosis. OBJECTIVE: To explore the experiences, preferences, and priorities of PwP around exercise and PA promotion and assess their knowledge on these topics. METHODS: A cross-sectional online survey for PwP in the United Kingdom was conducted from July to December 2021. RESULTS: 430 participants started the survey and 405 completed it. Participants had a mean age of 65.1 (±9.2) and had been living with Parkinson's for a varying time (up to 2 years = 38%, up to 6 years = 39% and for 7 or more years = 23%). Most participants reported they had not received an education (68%; n = 276) or exercise intervention (54%; n = 217) as part of their routine management by the National Health Service (NHS) since diagnosis and had sought services privately. Knowledge of the overall benefits of exercise was good, however participants lacked specific knowledge on the impact of Parkinson's Disease (PD) on posture, falls and muscle strength. 90% of participants reported they would participate in an exercise and PA education interventions. CONCLUSIONS: PwP want exercise and PA education interventions that provide knowledge, skills and access to opportunities that enable participation. For the majority, these interventions have not been provided as part of their routine care pathway. To align with the priorities and preferences of PwP, interventions should be offered around the time of diagnosis, include content that is relevant and specific to how exercise and PA can mitigate symptoms of PD and should be delivered in person or online in a group setting.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

BACKGROUND AND OBJECTIVES: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials. METHODS: We used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning. RESULTS: A total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint. DISCUSSION: The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Reduction in presynaptic dopamine transporter may be associated with future problematic delusion.

OBJECTIVES: Psychosis, especially in delusions, greatly impairs the quality of life of patients with Parkinson's disease (PD) and their caregivers. Few objective risk indicators of the association between psychosis and clinical features has been reported. It is unclear whether the reduction in DAT binding represents the underlying mechanism of delusion or its association. There are no long-term data on the objective prognostic value of DAT binding for delusions. We investigated whether DAT binding at baseline can be a prognostic risk factor for future development of PD delusions. MATERIALS AND METHODS: We reviewed the detailed clinical chart of patients with PD without a history of psychosis who underwent [123I]FP-CIT SPECT during the disease. The endpoint was defined as when the delusions occurred during the 5 years after the examination of [123I]FP-CIT SPECT. Specific binding ratio (SBR) values were calculated. RESULTS: Sixty-one patients with PD were included in the analysis, and 11 patients had delusions within 5 years of [123I] FP-CIT SPECT. The average (p = 0.004), minimum (p = 0.004), maximum (p = 0.001), right-sided (p = 0.002), and left-sided (p = 0.003) SBRs in the striatum were significantly smaller in patients with delusions than in patients without delusions. Each difference of each SBR was significantly smaller than those without delusions after adjusting after controlling for age, gender, disease severity, timing of [123I]FP-CIT SPECT, anti-parkinsonian medications, hospitalization, administering more or newly anti-parkinsonian drugs, and receiving DBS or LCIG. CONCLUSIONS: PD delusions is still problematic, and lowering DAT binding may be helpful for predicting future delusions, regardless of the timing of [123I]FP-CIT SPECT.

The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.

We investigated the correlation of orthostatic hypotension (OH) in Parkinson disease (PD) with the disease course and severity, and its possible impact on quality of life. 171 PD patients were recruited and divided into the PD-NOH (n = 91) and PD-OH groups (n = 80). Clinical data were collected. The severity and quality of life of PD patients were evaluated. The impact of disease severity was analyzed using logistic regression analysis. The ROC curve was plotted. There were significant differences (P < .05) between PD-NOH and PD-OH groups in terms of the disease course, non-motor symptoms (somnipathy), Hoehn&Yahr stage, LEDD score, RBDSQ score, PDQ-39 score, MMSE score, MoCA, MDS-UPDRS Part III scores during off- and on-periods, and NMSS score. Hoehn&Yahr stage (OR 4.950, 95% CI 1.516-16.157, P = .008) was closely associated with the risk of OH in PD. PDQ-39 score (OR 1.079, 95% CI 1.033-1.127, P = .001) in PD patients with OH further decreased. Patients with PD-OH experienced severe impairment in 4 dimensions of quality of life, including motor function, cognitive function, physical discomfort, and activities of daily living. Different clinical symptoms of PD-OH were positively correlated with PDQ39 subscales. The area under the ROC curve of the Hoehn&Yahr stage in predicting the occurrence of OH was 0.679 (95% CI 0.600-0.758), and that of the Hoehn&Yahr stage combined with levodopa equivalent dose, and MDS-UPDRS Part III score during off-period was 0.793 (95% CI 0.727-0.862). Higher Hoehn&Yahr stage is associated with increased risk of OH in PD patients, and deteriorated quality of life of PD patients. Patients with different OH symptoms are affected in different dimensions of their quality of life. The Hoehn & Yahr stage can independently predict the risk of OH in PD patients.

Changes in speech prosody perception during Parkinson's disease: A comprehensive analysis.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects approximately 1%-2% of individuals aged 60 and above. Communication disorders in PD can significantly impact the overall quality of life. As prosody plays a vital role in verbal communication, the present study examines Persian prosody perception in PD, focusing on linguistic and emotional aspects of prosody. METHODS: This cross-sectional study aimed to compare the perception of linguistic and emotional prosody in three groups: middle-aged adults (n = 22; mean age = 50.40 years), healthy older adults (n = 22; mean age = 68.31 years), and individuals with Parkinson's disease (n = 22; mean age = 65years). All individuals with PD were classified in stages 1; 1.5; 2; 2.5, and 3 of the disease using the Hoehn and Yahr scale. All participants had an MMSE score of 24 or above. The Florida Affect Battery (FAB) was used to evaluate prosody perception. This Battery was validated in the Persian language and its reliability and validity were reported as 94 % and 100 % respectively. RESULTS: Participants with PD presented significantly lower scores than the older adults in all subtests of the FAB (p < 0.05), while healthy older adults were significantly different only in linguistic discrimination (ß = -2.14; -3.68 to -0.61), and linguistic naming of prosody (ß = 1.25; 0.17 to 2.33) compared to middle-aged adults. CONCLUSIONS: The present study sheds light on the influence of PD on Persian prosody perception. Given the crucial role of prosody in verbal communication, these findings enhance our understanding of communication disorders in PD and could bring attention to consider prosody perception, among other aspects, when assessing individuals affected by PD.

Developments in the prediction of cognitive changes following deep brain stimulation in persons with Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) motor symptoms that improves function and quality of life in appropriately selected patients. Because mild to moderate cognitive declines can follow DBS and impact quality of life in a minority of patients, an important consideration involves the cognitive deficit and its prediction. AREAS COVERED: The author briefly summarizes cognitive outcomes from DBS and reviews in more detail the risks/predictors of post-DBS cognitive dysfunction by mainly focusing on work published between 2018 and 2024 and using comprehensive neuropsychological (NP) evaluations. Most publications concern bilateral subthalamic nucleus (STN) DBS. Comment is offered on challenges and potential avenues forward. EXPERT OPINION: STN DBS is relatively safe cognitively but declines occur especially in verbal fluency and executive function/working memory. Numerous predictors and risk factors for cognitive outcomes have been identified (age and pre-operative neuropsychological status appear the most robust) but precise risk estimates cannot yet be confidently offered. Future studies should employ study center consortia, follow uniform reporting criteria (to be developed), capitalize on advances in stimulation, biomarkers, and artificial intelligence, and address DBS in diverse groups. Advances offer an avenue to investigate the amelioration of cognitive deficits in PD using neuromodulation.

Hypersexuality in neurological disorders: A systematic review.

BACKGROUND: Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. Objective We aimed to systematically review the literature on HS in patients with neurological disorders. Study selection and analysis We conducted a systematic review to identify studies that reported HS in neurological disorders. HS was defined as a condition characterized by excessive and persistent preoccupation with sexual thoughts, urges, and behaviors that cause significant distress or impairment in personal, social, or occupational functioning. Data on demographics, assessment techniques, associated elements, phenotypic manifestations, and management strategies were also extracted. Findings The final analysis included 79 studies on HS, encompassing 32 662 patients across 81 cohorts with neurological disorders. Parkinson's disease was the most frequently studied condition (55.6%), followed by various types of dementia (12.7%). Questionnaires were the most common assessment approach for evaluating HS, although the techniques varied substantially. Alterations in the dopaminergic pathways have emerged as contributing mechanisms based on the effects of medication cessation. However, standardized treatment protocols still need to be improved, with significant heterogeneity in documented approaches. Critical deficiencies include risks of selection bias in participant sampling, uncontrolled residual confounding factors, and lack of blinded evaluations of reported outcomes. Conclusions and clinical implications Despite growth in the last decade, research on HS remains limited across neurological conditions, with lingering quality and methodological standardization deficits. Key priorities include advancing assessment tools, elucidating the underlying neurobiology, and formulating management guidelines. PROSPERO REGISTRATION NUMBER: CRD42017036478.

The lateralized effects of Parkinson's Disease on motor imagery: Evidence from mental chronometry.

Alterations to the content of action representations may contribute to the movement challenges that characterize Parkinson's Disease (PD). One way to investigate action representations is through motor imagery. As PD motor symptoms typically have a unilateral onset, disease-related deficits related to action representations may follow a similarly lateralized pattern. The present study examined if temporal accuracy of motor imagery in individuals with PD differed according to the side of the body involved in the task. Thirty-eight participants with PD completed a mental chronometry task using their more affected and less affected side. Participants had significantly shorter mental versus physical movement times for the more affected. Higher imagery vividness in the kinaesthetic domain predicted shorter mental versus physical movement times for the more affected side, as did lower imagery vividness in the visual domain and poorer cognitive function. These results indicate that people with PD imagine movements differently when the target actions their more affected versus less affected side. It is additionally possible that side-specific deficits in the accurate processing of kinaesthetic information lead to an increased reliance on visual processes and cognitive resources to successfully execute motor imagery involving the more affected side.

Role of virtual reality in examining the effect of fear of falling (FOF) on postural stability in individuals without and with Parkinson's disease in Egypt: a mixed-methods feasibility study protocol.

BACKGROUND: Falls are common in older people and individuals with neurological conditions. Parkinson's disease (PD) is known for postural instability causing mobility disabilities, falls and reduced quality of life. The fear of falling (FOF), a natural response to unstable balance, can worsen postural control problems. Evaluating FOF relies largely on affected persons' subjective accounts due to limited objective assessment methods available. The aim of this mixed-methods feasibility study is to develop an assessment method for FOF while in motion and walking within virtual environments. This study will assess a range of FOF-related responses, including cognitive factors, neuromuscular response and postural stability. METHODS AND ANALYSIS: This feasibility study will consist of four phases: the first two phases will include people without PD, while the other two will include people diagnosed with PD. Participants will be assessed for direct and indirect responses to real life, as well as virtual environment walking scenarios that may induce FOF. Data from questionnaires, different neurophysiological assessments, movement and gait parameters, alongside evaluations of usability and acceptability, will be collected. Semistructured interviews involving both participants and research assistants shall take place to elicit their experiences throughout different phases of the assessments undertaken. Demographic data, the scores of assessment scales, as well as feasibility, usability and acceptability of the measurement methods, will be illustrated via descriptive statistics. Movement and gait outcomes, together with neurophysiological data, will be extracted and calculated. Exploring relationships between different factors in the study will be achieved using a regression model. Thematic analysis will be the approach used to manage qualitative data. ETHICS AND DISSEMINATION: This feasibility study was approved by the Ethics Committee of the Faculty of Physical Therapy, Kafr El Sheikh University, Egypt (number: P.T/NEUR/3/2023/46). The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05931692).