BackgroundA key challenge in trials targeting disease modification in Parkinson's disease (PD) is the lack of sensitive, precise, and patient-relevant outcome measures. Digital mobility outcomes (DMOs), captured using bo...BackgroundA key challenge in trials targeting disease modification in Parkinson's disease (PD) is the lack of sensitive, precise, and patient-relevant outcome measures. Digital mobility outcomes (DMOs), captured using body-worn devices, offer a novel, objective means to assess real-world gait and mobility-domains often impaired early in PD. The Mobilise-D consortium was established to develop and validate DMOs in PD and other conditions.ObjectiveTo describe DMOs in a large, representative international cohort of individuals with PD and compare to controls and across disease stage; and to determine compliance and feasibility.MethodsAs part of the Mobilise-D Clinical Validation and Extension Studies, real-world mobility of individuals with PD (n = 601) and matched controls (n = 232) was assessed using a single wearable device for seven days. Data were processed to yield 24 technically validated DMOs, representing different domains of real-world walking and mobility performance.ResultsDMO data were available for 531 PD and 221 controls. Significant differences between the groups were observed in 20 of 24 DMOs. Compared to controls, PD participants exhibited shorter daily walking duration and lower step counts, walking at a higher cadence and in fewer walking bouts per day. Findings also varied by disease severity, with differences observed particularly between controls mild (Hoehn and Yahr stage I-II) and mild moderate (Hoehn and Yahr stage III) disease. Compliance rates were high.ConclusionsDistinct DMO patterns across PD severity and between PD and controls support their utility as sensitive, scalable outcome measures for future clinical trials and therapeutic development.
Classic accounts of 'kinesia paradoxa' typically involve highly stressful or life-threatening situations, which are difficult to translate to daily life. Here, we describe two patients with parkinsonism who successfully...Classic accounts of 'kinesia paradoxa' typically involve highly stressful or life-threatening situations, which are difficult to translate to daily life. Here, we describe two patients with parkinsonism who successfully apply self-induced 'arousal-heightening' strategies to improve their mobility. The first patient uses an electronically modified fly swatter to self-deliver a mild electrical shock, enabling him to overcome episodes of freezing of gait. The second patient uses his phone's alarm to alert himself, resulting in improved sit-to-stand transfer. These observations suggest that self-induced arousal-heightening strategies represent a hitherto underexplored compensatory strategy that could help to improve mobility in some individuals with parkinsonism.Plain language summary titleHelping people with Parkinson's disease move more easily using alertness tricks.
BackgroundParkinson's disease (PD) is associated with a high prevalence of cardiovascular dysfunction, a leading cause of mortality in these patients. Autonomic dysfunction, including cardiac autonomic dysfunction (CAD),...BackgroundParkinson's disease (PD) is associated with a high prevalence of cardiovascular dysfunction, a leading cause of mortality in these patients. Autonomic dysfunction, including cardiac autonomic dysfunction (CAD), is increasingly recognized as a significant non-motor symptom in PD and may contribute to adverse cardiac outcomes.ObjectiveTo investigate echocardiographic alterations in PD patients with CAD and evaluate their diagnostic utility for CAD detection.MethodsParticipants were categorized into PD-CAD and PD-nCAD groups based on Cardiovascular Autonomic Reflex Tests. Echocardiographic assessments included standard transthoracic echocardiography and two-dimensional speckle-tracking strain imaging. Multivariable regression was used to identify predictors of PD-CAD. Receiver operating characteristic curves, integrated discrimination improvementResultsA total of 78 participants were included, with a median Hoehn and Yahr stage of 2.00 [IQR 2.00, 2.50]. Among them, 33.33% were classified as having PD-CAD. Impaired systolic function characterized by decreasing left ventricular global longitudinal strain and lower systolic mitral annular velocity were found in PD-CAD group. A model combining LV-GLS, s', and LVMI predicted CAD with AUC = 0.737 (95% CI:0.624-0.850), comparable to conventional autonomic markers.ConclusionSubclinical systolic dysfunction (LV-GLS, s') reflects autonomic-mediated myocardial injury in PD and demonstrates diagnostic potential for CAD identification. Echocardiography may bridge autonomic dysfunction and cardiovascular risk in PD.
Parkinson's disease is the fastest growing neurodegenerative disorder worldwide, yet care delivery remains fragmented and inequitable. We propose a new construct called the Parkinson's Universe. It is a person-centered m...Parkinson's disease is the fastest growing neurodegenerative disorder worldwide, yet care delivery remains fragmented and inequitable. We propose a new construct called the Parkinson's Universe. It is a person-centered model that reimagines care as a coordinated universe. This commentary summarizes the model's elements including the patient as the sun or center of the universe, the caregiver as Mercury, the social support and multidisciplinary healthcare professionals as the other planets, mission control as care coordination, stigma as Pluto, barriers as asteroids, supportive technology as satellites, and support networks as stars. We discuss clinical and policy implications, emphasizing the urgent need to move beyond the fragmented gatekeeper system to one that is proactive, equitable, and holistic. As such, the Parkinson's Universe provides a blueprint for integrating innovation, advocacy, and multidisciplinary care. The model also has relevance across other complex chronic diseases.
Falcitano L, Calizzano F, Mattioli P
… +15 more, Kiersnowski OC, Avanzino L, Girtler NG, Diociasi A, Losa M, Massa F, Morbelli S, Orso B, Pelosin E, Bonassi G, Raffa S, Pardini M, Costagli M, Roccatagliata L, Arnaldi D
Background and objectiveNigrostriatal dopaminergic degeneration is commonly assessed using dopamine transporter (DaT) SPECT. Iron sensitive MRI is a promising technique to assess substantia nigra, yet few studies explore...Background and objectiveNigrostriatal dopaminergic degeneration is commonly assessed using dopamine transporter (DaT) SPECT. Iron sensitive MRI is a promising technique to assess substantia nigra, yet few studies explored its application in the prodromal stage of alpha-synucleinopathies. Here, we used susceptibility map weighted imaging (SMWI) to assess the swallow tail sign, a radiological marker for substantia nigra integrity, to detect neurodegeneration across the alpha-synucleinopathy continuum.Methods3T-MRI was performed on 115 subjects: 27 overt alpha-synucleinopathies, 34 prodromal alpha-synucleinopathies, 28 Alzheimer's disease and 26 healthy controls. SMWI was obtained with 3D multi-echo gradient-echo imaging. The presence/absence of the swallow tail sign was visually evaluated on SMWI by two neuroradiologists, blinded to the diagnosis. Swallow tail sign's visual assessment was compared across groups to investigate its sensitivity and specificity in identifying alpha-synucleinopathies. Additionally, we compared the SMWI visual analysis sign with both substantia nigra quantitative susceptibility mapping (QSM) and DaT-SPECT.ResultsThe two radiologists' inter-rater agreement was substantial (kappa = 0.8). Visual analysis showed good sensitivity (0.85) and specificity (0.82) in identifying patients with alpha-synucleinopathies. When the subjects were grouped based on DaT-SPECT results, sensitivity increased (0.92), while specificity decreased (0.74). Visual scoring was associated with quantitative substantia nigra MRI assessment obtained with QSM (p < 0.001). Lastly, subjects with the swallow tail sign rated as absent showed significantly lower (p = 0.019) uptake at DaT-SPECT (-1.857 ± 1.343) compared to those with the swallow tail sign rated as present (-0.385 ± 1.850).ConclusionsVisual analysis of SMWI swallow tail sign represents a new and reliable approach for evaluating substantia nigra neurodegeneration across the alpha-synucleinopathy continuum.
Parkinson's disease (PD) is a progressive neurodegenerative disease with multiple manifestations including both motor and non-motor symptoms. One manifestation of PD that is often overlooked is the sexual dysfunction (SD...Parkinson's disease (PD) is a progressive neurodegenerative disease with multiple manifestations including both motor and non-motor symptoms. One manifestation of PD that is often overlooked is the sexual dysfunction (SD) that patients may experience. Individuals with PD can experience impairment in sexual desire, arousal or lubrication, orgasm, ejaculation, pain and the physical aspect of intimacy. This article aims to provide an overview of the current practices in the evaluation and treatment of sexual dysfunction in men in the context PD. Note that this article focuses on the male population as it reviews the available American Urology Association practice guidelines many practitioners follow, which focus on the male population. Sexual dysfunction guidelines for the female population are much more limited, and future work should review the existing literature and gaps to provide a more robust understanding of sexual dysfunction in PD. PD represents a particularly vulnerable population for development of sexual dysfunction given the multifactorial nature of its manifestations. Given its profound impact on not only the patient, but their partner, it is important to be aware of the various manifestations of SD when evaluating individuals with PD. Through thorough history taking and targeted psychosexual evaluation, we as practitioners can ensure a more holistic and comprehensive approach to caring for individuals with PD.
Parkinson's disease is a common neurodegenerative disorder, which is characterised by motor features, many of which relate to the loss of the dopaminergic nigrostriatal pathway. The use of grafted cells to replace the lo...Parkinson's disease is a common neurodegenerative disorder, which is characterised by motor features, many of which relate to the loss of the dopaminergic nigrostriatal pathway. The use of grafted cells to replace the lost dopaminergic neurons as a therapy for Parkinson's has been explored since the 1980s, with mixed clinical outcomes. Much of the heterogeneity in outcomes has been related to the major problems with the cell source for these trials, being derived from human fetal brain tissue. It is, however, now possible to derive authentic midbrain dopamine cells from human pluripotent stem cells and several first-in-human clinical trials are now underway to explore this approach.
BackgroundParkinson's disease (PD) causes disability and premature mortality if untreated. Limited access to levodopa in low- and middle-income countries leaves many patients undertreated. (MP) is a leguminous plant tha...BackgroundParkinson's disease (PD) causes disability and premature mortality if untreated. Limited access to levodopa in low- and middle-income countries leaves many patients undertreated. (MP) is a leguminous plant that contains high concentrations of levodopa.ObjectiveTo demonstrate the non-inferiority of long-term intake of MP powder in terms of safety and efficacy compared to standard levodopa dopa-decarboxylase inhibitor (LD + DDCI).MethodsIn this 12-month, multicenter, randomized, open-label phase 2 trial, thirty-two untreated PD patients received levodopa monotherapy with MP powder -derived from roasted seeds without pharmacological processing- or standard LD + DDCI. Dosing was adjusted for body weight and disease stage, with MP doses further calibrated to account for the absence of a DDCI. We measured quality of life using the 39-item PD Questionnaire, motor and non-motor disability using the Movement Disorders Society updated version of the Unified PD Rating Scale (MDS-UPDRS) (parts I to IV) and the Non-Motor Symptoms Questionnaire. Safety measures included recording any adverse event and laboratory test.ResultsMP powder improved quality of life, motor and non-motor symptoms over 12 months, demonstrating similar outcome to LD + DDCI on all endpoints. Adverse events were more frequent with MP (56% vs. 37.5%, p = 0.48), though the difference was not statistically significant. Most were mild, with only 12.5% leading to discontinuation.ConclusionsMP could be a cost-effective alternative for PD individuals with limited access to commercial levodopa formulations. To confirm long-term safety and efficacy, larger international multicenter, double-blind trials with extended follow-up (e.g. 24-36 months) and ethnically diverse cohorts are needed.Registered at PACTR201611001882367.
BackgroundCognitive dysfunction is one of the most debilitating non-motor symptoms of Parkinson's disease (PD). This study aimed to explore the interplay between altered neurotransmitter activities, including dopamine an...BackgroundCognitive dysfunction is one of the most debilitating non-motor symptoms of Parkinson's disease (PD). This study aimed to explore the interplay between altered neurotransmitter activities, including dopamine and acetylcholine, and brain metabolism in cognitive decline in PD.MethodsWe enrolled 172 PD patients (mean ± SD age 69.8 ± 8.6 years; 93 females) who underwent brain magnetic resonance imaging, -(3-[F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (F-FP-CIT) positron emission tomography (PET), F-fluorodeoxyglucose (FDG) PET, and neuropsychological testing. General linear models and mediation analyses were used to investigate the association between striatal dopamine transporter (DAT) availability or basal forebrain (BF) volume, brain metabolism, and domain-specific cognitive scores.ResultsA significant relationship between caudate dopamine depletion and posterior BF atrophy was found in PD patients. Caudate and putaminal dopamine depletion were associated with altered brain metabolism in regions where PD patients showed decreased metabolism compared with healthy controls, whereas atrophy in the posterior BF was associated with hypometabolism in the lateral prefrontal, orbitofrontal, inferior parietal, and lateral temporal cortices as well as in the precuneus, with a significant interaction between caudate DAT availability and posterior BF volume. Caudate dopamine depletion was associated with visuospatial, memory, and executive dysfunction, whereas posterior BF atrophy was additionally associated with attention. Mediation analyses revealed that visuospatial dysfunction was associated with caudate dopamine depletion or posterior BF atrophy via altered brain metabolism, while executive dysfunction was linked to both directly and through metabolism changes.ConclusionsCaudate dopaminergic and posterior BF cholinergic deficits are interrelated and affect cognition in a domain-specific manner, either directly or through the mediation of altered brain metabolism.
BackgroundReactive astrocytes are one of the pathological features of Parkinson's disease (PD) and are associated with neuroinflammation and neuronal damage.ObjectiveTo explore the causal relationship between reactive as...BackgroundReactive astrocytes are one of the pathological features of Parkinson's disease (PD) and are associated with neuroinflammation and neuronal damage.ObjectiveTo explore the causal relationship between reactive astrocyte-related genes and PD through the summary data-based Mendelian randomization (SMR).MethodsWe combined these reactive astrocyte-related Quantitative Trait Loci (QTLs) data with PD genome-wide association study (GWAS) statistics. Using SMR, we explored causal links between gene expression, methylation and protein levels (pQTL) with PD, which were validated through colocalization analysis, replication cohorts and substantia nigra tissue data. The study also explored the causal relationship between DNA methylation and gene expression.ResultsSMR analysis identified 95 mQTLs (corresponding to 44 genes), 9 eQTLs, and 7 pQTLs nominally associated with PD (P-SMR_multi < 0.05 & P-SMR < 0.05, and P-HEIDI > 0.01). There was still a significant causal association between expression and Parkinson's disease risk after FDR correction (OR = 2.085, 95%CI = 1.463 to 2.972, P-HEIDI = 0.225, P-SMR = 0.013), supported by strong colocalization (PPH4 = 0.987). Similarly, there was a significant association between corrected CTSB protein levels and Parkinson's disease risk (OR = 0.855, 95%CI = 0.791 to 0.925, P-HEIDI = 0.076, P-SMR = 0.028). The methylation and expression of and were both nominally associated with the risk of PD. Further analysis revealed that there was also a causal relationship between their methylation and expression.ConclusionsWe identified the gene as a potential causative gene for PD. Its high expression was robustly causally associated with an increased risk of PD and was supported by strong colocalization evidence.
Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder, so it is likely that people with PD (PwPD) face increasing disability. PwPD thus experience various degrees of fear of progression (FoP), which...Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder, so it is likely that people with PD (PwPD) face increasing disability. PwPD thus experience various degrees of fear of progression (FoP), which can become dysfunctional. This study aims to examine the prevalence of and contributing factors to dysfunctional FoP in PwPD. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF) was administered along with further questionnaires for non-motor symptoms; PD motor symptoms as reported by the Unified Parkinson's Disease Rating Scale Part III (UPDRS III) were obtained from patient charts. 28% of the 105 PwPD (mean age 66 years, 56% Hoehn & Yahr stage I/II) were categorized as experiencing dysfunctional levels of FoP using the established cut-off score of ≥34. Our analyses revealed that the FoP-Q-SF underestimates the prevalence of dysfunctional FoP in older and non-working PwPD. Using a more appropriate cut-off, 33% of PwPD are classified as having dysfunctional levels of FoP. We found strong correlations of FoP with measures of anxiety, depression and quality of life. Disease duration was secondary to these factors. We found no associations between FoP and motor symptoms. Our findings confirm that dysfunctional FoP significantly impacts the psychological well-being of PwPD, affecting one in three PwPD and contributing to heightened anxiety, depression, and reduced quality of life. Future validation studies are needed to confirm the cut-off value proposed here and to enable a better integration of the concept of FoP into routine care for PwPD.
BackgroundDespite the widespread adoption of deep brain stimulation (DBS) for treating Parkinson's disease (PD) over the last few decades, standardized post-operative care protocols remain lacking.ObjectiveThis study aim...BackgroundDespite the widespread adoption of deep brain stimulation (DBS) for treating Parkinson's disease (PD) over the last few decades, standardized post-operative care protocols remain lacking.ObjectiveThis study aimed to establish expert consensus on managing post-operative subthalamic nucleus (STN-DBS).MethodsA three-round online Delphi study was conducted involving an international panel of DBS experts actively engaged in all facets of post-operative care. In the initial round, the panel generated ideas regarding essential components of a post-operative care protocol. In rounds two and three, numerical ratings and rankings were employed to achieve consensus on the formulated statements. This iterative process culminated in a refined STN-DBS care protocol.ResultsThe study included 76 international participants who, over three survey rounds, reached consensus on 129 components of a care protocol for managing post-operative STN-DBS. The final protocol encompassed eleven essential domains: hospital discharge, rehabilitation referral, imaging and lead review, monopolar testing, local field potential sensing, troubleshooting, medication management, multiprofessional care, follow-up, empowerment of patients and caregivers, and quality control of management procedures.ConclusionsThis Delphi-based, expert-driven process resulted in a comprehensive care protocol for patients undergoing STN-DBS. The findings offer a valuable resource for healthcare professionals, providing a structured, consensus-based framework aimed at optimizing post-operative outcomes. In addition to supporting clinical practice, these recommendations may help inform policy development and drive systematic improvements in care delivery. Further research and validation in diverse clinical settings will be essential to assess the generalizability and real-world impact of the proposed procedures.
IntroductionMetabolic covariance patterns derived from imaging data help characterize disease-related physiological changes in several neurodegenerative disorders, including Parkinson's disease (PD), but their relevance...IntroductionMetabolic covariance patterns derived from imaging data help characterize disease-related physiological changes in several neurodegenerative disorders, including Parkinson's disease (PD), but their relevance to different disease stages and/or clinical variables related to disease or disease predisposition, such as age, is often unclear.MethodsWe incorporated clinical information in deriving metabolic covariance patterns relevant to different aspects of PD: disease initiation, disease progression, and physiological similarities in PD and healthy aging. This was achieved by combining Partial Least Squares Correlation analysis with Scaled Subprofile Modeling (SSM-PLSC).ResultsWhen combining PD and HC data, SSM-PLSC identified a spatial pattern similar to the well-known PD-related disease pattern as expected; when applied to PD-only data-thus emphasizing disease progression-the spatial pattern became characterized by expanding putaminal hypermetabolism and reduced emphasis on cerebellar hypermetabolism. Finally, when applied to PD and HC data but permitting a different dependence on clinical variables, SSM-PLSC identified a spatial pattern with relative hypermetabolism in the basal ganglia, brain stem, and white matter together with relative hypometabolism in frontal cortex; in HC this pattern solely related to age, while in PD the same pattern significantly correlated with both age and disease duration.ConclusionWe identified metabolic patterns that are more closely related with different aspects of PD, directly derived from relationships between metabolic alterations and clinical variables. We also revealed metabolic signatures common to PD and aging, which may highlight age-related metabolic changes that form a predisposition to PD, as age is the single highest risk factor for PD.Plain language summary titleBrain changes in Parkinson's disease and their relationship to clinical aspects of disease.
The subtyping of Parkinson's Disease (PD) into brain-first and body-first PD has a powerful neuropathological, neuroimaging and clinical basis, supported by most relevant subsequent studies that have examined its validit...The subtyping of Parkinson's Disease (PD) into brain-first and body-first PD has a powerful neuropathological, neuroimaging and clinical basis, supported by most relevant subsequent studies that have examined its validity. Here, we put forward the idea that the previous classification into early and late onset PD may be related to this categorization. The mean age of motor onset in brain-first PD may be up to 10 years earlier than body-first PD. Early onset PD has features related to brain-first PD, including relative clinical and nigrostriatal neurodegeneration asymmetry and a relatively restricted motor phenotype. In fact, PD as described by James Parkinson, could represent both early onset and brain-first PD, accounting for the famous phrase "senses and intellect uninjured". We suggest here that, at the population level, age of onset could be used as a proxy for brain-first vs body-first PD, notwithstanding the lack of a direct one-to-one correlation and of a clear dichotomy in early vs. late onset PD, which rather represents a continuum. This would enable large scale population studies into the underlying genetic and epidemiological basis of these presumed separate nosological entities. Along these lines, there are some indications of a divergent exposure and genetic basis in early vs. delayed onset PD, and body-first vs. body-first PD respectively. Thus, studies of the etiopathological basis of PD could examine data sets with clinical data limited to age of onset, keeping in mind that within the overall concept of sporadic PD there may be two qualitatively different disease processes.
IntroductionThere are conflicting findings regarding the influence of sex on idiopathic REM sleep behavior disorder (iRBD) in terms of prevalence and associated clinical characteristics. This study, conducted as part of...IntroductionThere are conflicting findings regarding the influence of sex on idiopathic REM sleep behavior disorder (iRBD) in terms of prevalence and associated clinical characteristics. This study, conducted as part of the Italian multicenter longitudinal FARPRESTO project, aims to explore sex-related differences in the age of onset, iRBD diagnosis, and phenoconversion, as well as in cognitive and non-motor features and the occurrence of RBD-related injuries among male and female patients with iRBD.MethodsThe FARPRESTO study included 536 iRBD patients recruited from 13 Italian centers. This analysis assessed the age at iRBD diagnosis, diagnostic delay, motor and non-motor symptoms, global cognitive performance, conversion rates to neurodegenerative disorders, and the prevalence of RBD-related injuries at the time of iRBD diagnosis, stratified by sex.ResultsFemale patients were older at iRBD diagnosis compared to males (males: 67.8 years, IQR 62.5-72.6; females: 69.8 years, IQR 65.1-74.8; p = 0.003). Compared to male patients, female patients exhibited a higher prevalence of orthostatic hypotension (27.9% vs. 16.2%; p = 0.019), depression (43.9% vs. 26.6%; p = 0.010), and hallucinations (43.9% vs. 26.6%; p = 0.010) at iRBD diagnosis. Additionally, self-directed injuries were significantly more frequent in females compared to males at the first visit (71% vs. 53.2%; p = 0.034). No significant differences were observed in the phenoconversion rate between sexes.ConclusionAlthough research on sex-related differences in iRBD remains limited, this study highlights the importance of understanding sex-specific characteristics. As diagnostic and therapeutic approaches evolve, incorporating these differences will be essential for tailoring clinical strategies and improving patient outcomes.
Gigante AF, Vitucci B, Velucci V
… +18 more, Pellicciari R, Modugno N, Pietracupa S, De Bartolo MI, Costanzo M, Terravecchia C, Mascia MM, Muroni A, Ercoli T, Solla P, Magrinelli F, Conte A, Fabbrini G, Nicoletti A, Tinazzi M, Berardelli A, Defazio G, Belvisi D
BackgroundThe role of dietary factors as risk or protective factors for Parkinson's disease (PD) remains debated.ObjectiveThis retrospective case-control study aimed to evaluate the associations between foods identified...BackgroundThe role of dietary factors as risk or protective factors for Parkinson's disease (PD) remains debated.ObjectiveThis retrospective case-control study aimed to evaluate the associations between foods identified through a data-driven analysis and PD, and to compare the relevance of dietary versus non-dietary factors as contributors to PD risk.MethodsThe study included 680 PD patients and 612 matched controls recruited from six Italian neurology centers. Dietary data were collected using a validated 77-item food frequency questionnaire, and factor analysis was conducted to identify groups of correlated foods (i.e., factors). Logistic regression models were used to assess the associations between these factors and PD, while non-dietary factors were subsequently included in the model for comparison.ResultsSeven factors were identified, four of which were significantly associated with PD. High consumption of sweets (Factor 1), red meat (Factor 3), and processed meats (Factor 6) was associated with an increased PD risk, whereas a high fruit intake (Factor 2) was protective. These associations remained significant after adjusting for other known non-dietary risk/protective factors. While the increased PD risk associated with dietary factors was weaker than that of non-dietary factors, protective dietary and non-dietary factors showed comparable effects in reducing PD risk.ConclusionsData-driven analysis identified foods potentially influencing PD risk, although non-dietary factors demonstrated a greater impact on PD risk. These findings highlight the need to integrate both diet and lifestyle habits into future PD research and prevention strategies.
The present study aimed to provide an overview of the experiences of couples coping with Parkinson's disease (PD), along with a synthesis of the mechanisms involved in changes within the couple's relationship in the cont...The present study aimed to provide an overview of the experiences of couples coping with Parkinson's disease (PD), along with a synthesis of the mechanisms involved in changes within the couple's relationship in the context of PD. These mechanisms were identified using a qualitative approach: dyadic Interpretative Phenomenological Analysis. Forty-five couples separated in three groups according to disease progression, participated. Interviews were conducted separately with each partner. After individual analysis, the salient individual and dyadic phenomena were identified at the group level. Three mechanisms emerged regardless of disease stage: having divergent views on PD, being united and cohesive, avoiding discussing the disease. Other mechanisms were more specific to some stages. Even with few consequences on independence, PD can significantly impact the couple's dynamics. In most cases, strategies for adjusting to PD and/or the changes it causes in the couple's relationship lead to tension and negative emotions. Better support for both partners is needed to promote better adjustment strategies from the early stage of PD.