Non-motor Symptoms Burden Research Articles

Caregiver Burden and Quality of Life in Late Stage Parkinson's Disease.

Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease involving both motor and non-motor symptoms (NMS). In the late stage of the disease, Hoehn and Yahr (HY) stages IV-V, the symptomatology is often severe and patients become increasingly dependent on help in their daily life, resulting in an increased burden for the informal caregivers. To assess the implications of the caregiver burden, caregiver quality of life (QoL) was assessed in 74 informal caregivers to patients in late stage PD, by the Alzheimer’s Patient Partners Life Impact Questionnaire (APPLIQue), which has been found useful also in PD. The majority of caregivers were the spouse/partner. Individual items provided information on which aspects of caregiver burden were the most common, i.e., items: “feel guilty if not there” (71% affirmed), “situation wears me down” (65% affirmed) and “always on my mind” (61% affirmed). In simple linear regression analyses, female patient gender (p = 0.007), better cognition (p = 0.004), lower NMS burden (p = 0.012) and not being the partner (p = 0.022) were associated with better caregiver QoL. Multivariable linear regression analyses identified better cognition (p = 0.004) and female patient gender (p = 0.035) as independently associated with better informal caregiver QoL. Identifying and treating NMS as well as recognizing and alleviating caregiver burden seem essential to enhance QoL for both patients and caregivers in late stage PD.

Prevalence and genotype-phenotype correlations of GBA-related Parkinson disease in a large Chinese cohort.

Background and purposeVariants in the glucocerebrosidase (GBA) gene are recognized as a common and important genetic risk factor for Parkinson disease (PD). However, the impact of variant severity on the clinical phenotype of PD in the Chinese population remains unclear. Thus, the present study aimed to determine the frequency of GBA‐related PD (GBA‐PD) and the relationship of GBA variant severity with clinical characteristics in a large Chinese cohort.MethodsLong‐range polymerase chain reaction and next generation sequencing were performed for the entire GBA gene. GBA variant severity was classified into five classes: mild, severe, risk, complex, and unknown.ResultsAmong the total 737 PD patients, 47 GBA variants were detected in 79 (10.72%) patients, and the most common GBA variants were R163Q, L444P, and R120W. Complete demographic and clinical data were obtained for 673 patients, which revealed that 18.50% of early onset PD patients had GBA variants. Compared with patients without GBA variants, GBA‐PD patients experienced PD onset an average of 4 years earlier and had more severe motor and nonmotor symptoms. Patients carrying severe and complex variants had a higher burden of nonmotor symptoms, especially depression, and more mood/cognitive and gastrointestinal symptoms than patients carrying mild variants.Conclusions GBA‐PD is highly prevalent in the Chinese population. The severity of GBA variants underlies distinct phenotypic spectrums, with PD patients carrying severe and complex variants seeming to have similar phenotypes. PD patient stratification by GBA variant severity should become a prerequisite for selecting specific treatments.

Clinical Markers of 6 Pre-dominant Coping Behaviors in Living With Parkinson Disease: A Convergent Mixed Methods Study.

People with Parkinson's disease (PwP) experience a variety of symptoms and fluctuations in these, which they have to cope with every day. In tailoring a person-centered treatment to PwP there is a lack of knowledge about the association between pre-dominant coping behaviors and clinical markers among PwP. To describe and compare specific clinical markers between 6 suggested coping behaviors. Thirty-four PwP, who previously had been classified into 6 different pre-dominant coping behaviors, were included in this mixed methods study. Six primary variables were included in the descriptive analysis; motor function (UPDRS-III), non-motor symptoms score (NMS-Quest), change in bradykinesia score, apathy score (LARS), personality traits (NEO-FFI), and cognitive status (evaluated by a neuropsychologist). The merged results of this mixed methods study indicate that clinical markers as apathy, burden of non-motor symptoms, cognitive impairments and personality traits, have the potential to impact the coping behavior in PwP. In a clinical setting the markers; NMS-burden, degree of apathy, cognition, and personality traits may indicate specific coping behavior. Three of the six suggested typologies of coping behaviors differed from the other groups when comparing descriptive data. In order to improve patient care and guide the development of person-centered therapies, each PwP should be approached based on those typologies.

Association of serum uric acid and non-motor symptoms in Parkinson's disease: A cross-sectional study from a movement disorders clinic in Lagos, Nigeria

Background and Objective: The role of serum uric acid (SUA) as a biomarker in Parkinson's disease (PD) remains exploratory and has not been described in our population. The objective of this study was to explore the profile of SUA and its relationship to nonmotor symptoms (NMS) burden in PD. Methods: This cross-sectional study recruited 70 persons with PD and 140 matched healthy controls in Lagos, Nigeria. PD was diagnosed using the United Kingdom PD Society Brain Bank criteria. NMS were assessed with the NMS Questionnaire (NMS-Quest). SUA was measured using standard methods. Results: The mean ages of PD and controls were 63 ± 9.4 years and 62.9 ± 8.8 years, respectively (P = 0.65), with no difference when compared by sex. The median PD duration (interquartile range [IQR]) was 4 (4.25) years. Median Hoehn and Yahr stage (IQR) was 2.5 (1.0). The mean total unified Parkinson's disease rating scale score was 70.7 ± 23.7. The mean NMS-Quest score was 8.5 ± 3.8. Mean SUA level was significantly lower in PD compared to controls (2.42 ± 0.75 mg/dL vs. 3.73 ± 1.09 mg/dL [P = 0.000]). There was a nonsignificant inverse linear trend of association (r = −0.184; P = 0.126) between the total NMS-Quest score and SUA level in PD. Logistic regression analysis revealed hyposmia and memory impairment were significantly related to lower SUA levels (P = 0.02 and P = 0.04, respectively). Conclusion: Our study corroborates the potential of SUA as a serum biomarker in PD and a possible role in defining non-motor symptom burden. Further exploration to clarify the association and interrogate the impact of interventions is warranted.

Parkinson's disease and Covid-19: Is there an impact of ethnicity and the need for palliative care.

Under the traditional models of care for People with Parkinson's Disease (PD, PwP), many of their needs remain unmet and a substantial burden of motor and non-motor symptoms they experience may not be tackled sufficiently. An introduction of palliative care (PC) interventions early in the course of PD offers profound benefits: it may improve quality of life of patients, their families and caregivers through the prevention and relief of medical symptoms, while, at the same time, emphasizing their emotional needs and spiritual wellbeing, establishing goals of care, and engaging in the advance care planning (ACP).The ongoing Coronavirus Disease 2019 (Covid-19) pandemic poses an unprecedented set of challenges for PwP and has in many ways (both directly and indirectly) magnified their suffering, thus rapidly raising the demand for PC interventions. Covid-19, as well as the repercussions of prolonged mobility restrictions and limited health-care access might exacerbate the severity of PD motor symptoms and interact negatively with a range of non-motor symptoms, with a detrimental effect on quality of life. Greater motor disability, higher amount of levodopa-induced motor fluctuations with an increased daily off-time, fatigue, anxiety, depression, sleep disturbances, pain and worsening of cognitive complaints might dominate the clinical presentation in PwP during the Covid-19 pandemic, alongside raising psychological and spiritual concerns and anticipatory grief.Here, we aim to provide a foundation for pragmatic and clinically orientated PC approach to improve quality of life and relieve suffering of PwP in the context of the current, ongoing Covid-19 pandemic.

The impact of nonmotor symptom burden on sexual function.

Sexual dysfunction (SD) is defined as a combination of reduction in libido, and problems with a person's ability to have sex. It is a frequent but neglected and poorly recognized nonmotor symptom (NMS) in Parkinson's disease (PD) which correlates with reduced quality of life (QoL). Hypersexuality forms another spectrum of SD and is an impulse control disorder (ICD) of behavior, which also affects the sexual desires of people with Parkinson's (PwP) and impacts their partner, family, and QoL. NMS occur in various forms and represents a range of symptoms, from cognitive dysfunction to pain and SD, and this chapter explores the relationship of comorbid NMS with SD and also how NMS, motor symptoms, and hypersexuality experienced by patients may impact sexual function in people with Parkinson's (PwP).

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P< 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P= 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P= 0.000). The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.

Longitudinal evolution of non-motor symptoms in early Parkinson\u2019s disease: a 3-year prospective cohort study

The progression of global non-motor symptoms (NMS) in Chinese patients with Parkinson’s disease (PD) has not been explored. We aimed to examine the longitudinal evolution of overall NMS in a 3-year prospective Chinese cohort with early-stage PD. We included 224 patients with early PD who underwent annual evaluation of motor and non-motor symptoms. NMS was assessed using the non-motor symptoms scale (NMSS). We observed an increased number of NMS in the majority of the NMSS domains except mood/apathy and sexual dysfunctions. Significant deterioration was observed in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains during the follow-up (P < 0.05). Notably, the number and the score of sexual dysfunctions decreased with the progression of the disease. All NMSS domains showed a small effect size from baseline to 1-, 2-, and 3-year follow-ups (effect size < 0.5). The generalized estimating equations model indicated that the total number of NMS was significantly associated with age and the Unified Parkinson’s Disease Rating Scale (UPDRS) III score (P < 0.05). Multiple logistic regression indicated that a high number of NMS at baseline was associated with a 3-point, a 6-point, and a 9-point increase in the UPDRS III score from baseline to 1-year (odds ratio [OR] 1.074, P = 0.017), 2-year (OR 1.113, P = 0.001), and 3-year (OR 1.117, P < 0.001), respectively. Our study indicated that overall NMS evolution in early PD is mild and multidimensional; a high NMS burden in early PD predicts the faster motor progression of PD. Our study is helpful for understanding the longitudinal evolution of NMS in PD.

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson's Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up.

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.

Neuropsychiatric and Cognitive Deficits in Parkinson's Disease and Their Modeling in Rodents.

Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.

Diplopia in Parkinson's disease: Indication of a cortical phenotype with cognitive dysfunction?

Visual disturbances are increasingly recognized as common non-motor symptoms in Parkinson's disease (PD). In PD patients, intermittent diplopia has been found to be associated with the presence of visual hallucinations and the Parkinson's psychosis spectrum. Here, we investigated whether diplopia in PD is associated with other non-motor traits and cognitive impairment. We investigated 50 non-demented PD patients with and without intermittent diplopia and 24 healthy controls for visual disturbances, as well as motor and non-motor symptoms. All participants underwent a neuropsychological test battery; visuospatial abilities were further evaluated with subtests of the Visual Object and Space Perception Battery (VOSP). The two PD patient groups did not differ significantly in age, symptom duration, motor symptom severity, frequency of visual hallucinations, or visual sensory efficiency. PD patients with diplopia reported more frequent non-motor symptoms including more subjective cognitive problems and apathy without changes in global cognition measures compared to those without diplopia. PD patients with diplopia had greater impairment in several tests of visuospatial function (pentagon copying p=.002; number location p=.001; cube analysis p<.02) and object perception (p<.001) compared to PD patients without diplopia and healthy controls. By contrast, no consistent group differences were observed in executive function, memory, or language. PD patients with diplopia have a greater non-motor symptom burden and deficits in visuospatial function compared to PD patients without diplopia. PD patients with diplopia might be prone to a cortical phenotype with cognitive decline and apathy associated with worse prognosis.

Effects of safinamide on non-motor, cognitive, and behavioral symptoms in fluctuating Parkinson\u2019s disease patients: a prospective longitudinal study

IntroductionParkinson’s disease (PD) patients in chronic levodopa treatment may experience motor and non-motor fluctuations, which may affect their quality of life. Safinamide is a new monoamine oxidase B inhibitor, also exerting a non-dopaminergic effect, recently approved as add-on therapy in fluctuating PD patients.MethodsWe performed a longitudinal prospective study in a cohort of 20 fluctuating PD patients, to test whether safinamide 50 mg may improve non-motor, cognitive, and behavioral symptoms over a 6-month treatment period. At each timepoint, clinical features were assessed by means of validated PD-specific scales. Neuropsychological assessment was performed by exploring all five cognitive domains.ResultsCompared to baseline, significant improvement was found in PD patients at 6-month follow-up in items investigating interest (p = 0.02), motivation (p = 0.02), and urinary disturbances (p = 0.03). Moreover, neuropsychiatric assessment showed a significant decrease in fatigue and apathy scores (p = 0.02 and p = 0.01, respectively). Motor assessment revealed a significant reduction in the total wake-up time spent in OFF state (p = 0.01). Follow-up neuropsychological evaluation did not reveal any change compared to baseline.ConclusionsOur data reveal that, along with motor fluctuation improvement, treatment with safinamide 50 mg may significantly decrease non-motor symptom burden in PD patients. Interestingly, non-dopaminergic mechanisms, such as glutamatergic overdrive, have been demonstrated to play a role in many pathways underlying these symptoms. Thus, we hypothesize that the neurotransmitter receptor-binding profile of safinamide may explain our findings.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Introduction In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and Methods Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Cross-sectional analysis of the Parkinson\u2019s disease Non-motor International Longitudinal Study baseline non-motor characteristics, geographical distribution and impact on quality of life

Growing evidence suggests that non-motor symptoms (NMS) in Parkinson’s disease (PD) have differential progression patterns that have a different natural history from motor progression and may be geographically influenced. We conducted a cross-sectional analysis of 1607 PD patients of whom 1327 were from Europe, 208 from the Americas, and 72 from Asia. The primary objective was to assess baseline non-motor burden, defined by Non-Motor Symptoms Scale (NMSS) total scores. Other aims included identifying the factors predicting quality of life, differences in non-motor burden between drug-naïve and non-drug-naïve treated patients, and non-motor phenotypes across different geographical locations. Mean age was 65.9 ± 10.8 years, mean disease duration 6.3 ± 5.6 years, median Hoehn and Yahr stage was 2 (2–3), and 64.2% were male. In this cohort, mean NMSS scores were 46.7 ± 37.2. Differences in non-motor burden and patterns differed significantly between drug-naïve participants, those with a disease duration of less than five years, and those with a duration of five years or over (p ≤ 0.018). Significant differences were observed in geographical distribution (NMSS Europe: 46.4 ± 36.3; Americas: 55.3 ± 42.8; Asia: 26.6 ± 25.1; p < 0.001), with differences in sleep/fatigue, urinary, sexual, and miscellaneous domains (p ≤ 0.020). The best predictor of quality of life was the mood/apathy domain (β = 0.308, p < 0.001). This global study reveals that while non-motor symptoms are globally present with severe NMS burden impacting quality of life in PD, there appear to be differences depending on disease duration and geographical distribution.

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson's Disease: A Longitudinal Analysis of Two International Cohorts.

Constipation is regarded as one of the prodromal features of Parkinson's disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson's Progression Markers Initiative [PPMI] study). Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

Progression of Nonmotor Symptoms in Parkinson's Disease by Sex and Motor Laterality.

Nonmotor symptoms (NMS) in Parkinson's disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson's Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson's progressed. In conclusion, males experienced increased NMS burden in Parkinson's disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients' quality of life by therapeutically alleviating nonmotor symptoms.

Factors Associated with Health-Related Quality of Life in Late-Stage Parkinson's Disease.

There is limited knowledge on health-related quality of life (HRQoL) in late-stage Parkinson's disease (PD). To assess factors associated with HRQoL in patients with late-stage PD, with a focus on health care provision. The Care of Late Stage Parkinsonism (CLaSP) project is the largest study on late-stage PD to date. The current study analyzed data of 401 patients from 6 European countries in whom HRQoL was assessed with the 8-item PD Questionnaire in patients without dementia. Factors potentially associated with HRQoL were assessed and examined in linear regression analyses. Better HRQoL was associated with living at home, greater independence in activities of daily living (Schwab and England Scale), less severe disease (Hoehn and Yahr stage), better motor function (Unified PD Rating Scale Part III), and lower non-motor symptoms burden (Non-Motor Symptoms Scale [NMSS]) across all NMSS domains. Having a PDspecialist as physician for PD, contact with a PDnurse, and no hospital admission during the past 3 months were associated with better HRQoL, but having seen a physiotherapist or occupational therapist was associated with worse HRQoL. The results emphasize the importance of optimizing treatment for motor and multiple non-motor symptoms to improve HRQoL in patients with late-stage PD. PD-specific health care resources, particularly PDnurses, are likely important in addressing issues to improve HRQoL in this population. Worse HRQoL in those who had recently seen a physiotherapist or occupational therapist may reflect referral based on factors not measured in this study.

Safinamide Improves Non-Motor Symptoms Burden in Parkinson's Disease: An Open-Label Prospective Study.

Some studies observed a benefit of Parkinson’s disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson’s disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years; 58% females; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4; p < 0.0001). By domains, improvement was observed in sleep/fatigue (−35.8%; p = 0.002), mood/apathy (−57.9%; p < 0.0001), attention/memory (−23.9%; p = 0.026), gastrointestinal symptoms (−33%; p = 0.010), urinary symptoms (−28.3%; p = 0.003), and pain/miscellaneous (−43%; p < 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4; p < 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.