Colonic diverticular disease: A new risk factor for Parkinson's disease?

BackgroundColonic diverticular disease is a chronic gastrointestinal disorder. Previous studies have suggested that chronic gastrointestinal tract is involved in the pathophysiology of Parkinson's disease.ObjectThis study investigated the potential link between colonic diverticular disease and risk of Parkinson's disease.MethodsData in this nationwide population-based cohort study were obtained from the National Health Insurance Research Database. Patients with colonic diverticular disease were identified from among 23.22 million insured Taiwanese residents who had been diagnosed between 2000 and 2005 and were aged ≥20 years (n = 23367). The comparison cohort included patients without colonic diverticular disease, matched by sex, age, and all comorbidities with the colonic diverticular disease patients cohort (n = 23367). Using univariable and multivariable Cox proportional hazard regression models, we estimated the adjusted hazard ratio (aHR) for PD with a 95% confidence interval (CI) after adjusting for age, sex, and all of comorbidities.ResultsThe risk of Parkinson's disease was higher in the CDD cohort than in the comparison cohort (HR = 1.27, 95%CI = 1.10–1.47). Compared with patients aged ≥65 years without CDD, the CDD patients in the equal age group had a 1.25-fold increased risk of PD (95% CI = 1.07–1.46).ConclusionColonic diverticular disease may be associated with an increased risk of Parkinson's disease. Thus, the risk of this neurodegenerative disease should be considered in patients with colonic diverticular disease.     

Attentional dysfunction and the punding spectrum in Parkinson's disease

BackgroundPunding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD.MethodsWe extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors—adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age—using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale.ResultsIn GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79–0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45–0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22–5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32–5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20–2.00); p < 0.001), but not hobbyism.ConclusionAttentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.     

Effects of socioeconomic status on mortality after Parkinson's disease: A nationwide population-based matched cohort study in Korean populations

IntroductionTo evaluate the mortality rate and impact of SES on mortality in PD using a nationwide cohort in Korea.MethodsWe selected patients diagnosed with PD (ICD-10 code: G20) and registration code for PD (V124) in the program for rare intractable diseases between 2004 and 2015. After that, atypical parkinsonism was excluded. A matched cohort of individuals without PD were enrolled by randomly matching patients by sex, age, and year of diagnosis to the PD group with a ratio of 1:9. Cox proportional hazard models were used to identify the effects of SES on mortality using Hazard Ratios and 95% confidence intervals.ResultsIn total, 26,570 participants were enrolled. The mortality rate was 30.37% in PD cohort and 16.69% in the comparison cohort. According to income level, PD patients in low-middle group revealed significantly decreased HRs of 0.704 (95% CI, 0.533–0.930) compared to those in the lowest group. The medical aid group showed an increased mortality rate (HR = 1.552, 95% CI, 1.191–2.021) compared to the national health insurance group. In the subgroup analyses, medical aid was associated with mortality only in PD with female (HR = 1.740, 95% CI, 1.242–2.438) or aged 60–79 years (HR = 1.434, 95% CI 1.005–2.045). There was no significant difference in mortality rate according to residential area in PD.ConclusionsIn Korea, individual level low SES including income level and insurance type were significantly associated with increased mortality, whereas regional level SES (residential area) was not related with mortality on PD.     

Constipation and risk of Parkinson’s disease: A Danish population-based cohort study

ObjectivesTo examine long-term associations between constipation and Parkinson’s disease (PD) in men and women, we conducted a population-based cohort study using prospectively collected registry data on hospital contacts for constipation and PD, stratified by follow-up time and sex.MethodsWe linked Danish registries to construct a cohort of all patients in Denmark with an outpatient hospital diagnosis of constipation 1995–2012 and a matched general population comparison cohort. Using Cox regression, we computed hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders, stratified by sex and follow-up time.ResultsThe 31,905 patients with constipation had a higher risk of PD than 159,092 comparison cohort members (adjusted (a) HR = 3.03, 95% CI 2.50–3.66), which was sustained to 11–15 years follow-up (aHR = 3.65, 95% CI 1.67–7.95). Increased risk was apparent in both sexes but stronger in men [aHR = 3.52 (2.67–4.64] than women [aHR = 2.64 (95% CI 2.02–3.44].ConclusionIn this large population-based cohort study, constipation was associated with sustained increased risk of a PD diagnosis, and the relative risk was higher for men than for women.     

Personality and addictive behaviours in early Parkinson's disease and REM sleep behaviour disorder

IntroductionChanges in personality have been described in Parkinson's disease (PD), with suggestion that those with established disease tend to be risk averse with a disinclination for addictive behaviour. However, little is known about the earliest and prodromal stages. Personality and its relationship with addictive behaviours can help answer important questions about the mechanisms underlying PD and addiction.Methods941 population-ascertained PD subjects within 3.5 years of diagnosis, 128 patients with rapid eye movement sleep behaviour disorder (RBD) and 292 control subjects were fully characterised for motor symptoms, non-motor symptoms and across the following 5 personality domains: 1) neuroticism 2) extraversion 3) conscientiousness 4) agreeableness 5) openness using the Big Five Inventory.ResultsPatients with early PD were more neurotic (p < 0.001), less extraverted (p < 0.001) and less open than controls (p < 0.001). RBD subjects showed the same pattern of being more neurotic (p < 0.001), less extraverted (p = 0.03) and less open (p < 0.001). PD patients had smoked less (p = 0.02) and drunk less alcohol (p = 0.03) than controls, but caffeine beverage consumption was similar. Being more extraverted (p < 0.001), more open (p < 0.001), and less neurotic (p < 0.001) predicted higher alcohol use, while being more extravert (p = 0.007) and less agreeable (p < 0.001) was associated with smoking more.ConclusionsA similar pattern of personality changes is seen in PD and RBD compared to a control population. Personality characteristics were associated with addictive behaviours, suggestive of a common link, but the lower rates of addictive behaviours before and after the onset of motor symptoms in PD persisted after accounting for personality.     

Fatigue correlates with LRRK2 G2385R variant in Chinese Parkinson's disease patients

IntroductionFatigue is common in patients with Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) G2385R variant predisposes individuals to develop PD in China. The aim of this study was to evaluate whether the LRRK2 G2385R variant is associated with fatigue in patients with PD.MethodsFatigue was evaluated by the Parkinson Fatigue Scale (PFS) in 329 PD patients and 180 controls, a cut-off score of ≥3.3 was used to define the presence of fatigue. All the enrolled PD patients were assessed by a comprehensive battery of motor and non-motor questionnaires. PD patients were genotyped for the G2385R variant. Associations of fatigue with the clinical assessments and with the G2385R variant in PD patients were analyzed by logistic regression.ResultsFatigue frequency was 55.62%. A logistic regression model found that the female sex (OR = 10.477; 95%CI: 2.806–39.120; p < 0.001), motor function (OR = 1.060; 95%CI: 1.012–1.110; p = 0.013), sleep disturbance (OR = 0.943; 95%CI: 0.910–0.976; p = 0.001) and depression severity (OR = 0.843; 95%CI: 0.736–0.965; p = 0.013) collectively predict the presence of fatigue in PD patients. After adjustment for demographics and associated clinical factors, the G2385R variant was associated with an increased risk for the presence of fatigue (OR = 10.699; 95% CI = 2.387–47.958; p = 0.002) in the PD population in this study.ConclusionWe confirm that fatigue in PD patients is common, and we have strengthened the associations between fatigue and female sex, motor severity and non-motor symptoms, particularly depression and sleep disturbances. Overall, we found that carriers of the G2385R variant were more prone to fatigue than non-carriers in PD patients.     

Cognitive impairment in Parkinson's disease: Associations between subjective and objective cognitive decline in a large longitudinal study

BackgroundCognitive decline creates substantial morbidity and cost in Parkinson's disease (PD) and clinicians have limited tools for counseling patients on prognosis. We aimed to use data from a randomized, controlled trial of isradipine in Parkinson's disease (STEADY-PD III) to determine which objective cognitive domain deficits drive patient complaints of cognitive symptoms.MethodsNeuro-Quality of Life (Neuro-QoL) Cognition: General Concerns (GC), and Cognition: Executive Function (EF) (subjective measures), were administered at baseline, 1, 2, and 3 years in 324 people with PD. Baseline Montreal Cognitive Assessment (MoCA) was divided into 4 domains: visuospatial/executive, memory, attention, and language (objective measures). Spearman rank correlations and multiple regression models adjusted for other clinical variables evaluated associations between baseline Neuro-QoL domains and individual MoCA domains. Multiple regression models evaluated the association between baseline MoCA domain performance and Neuro-QoL change over three years. Cox proportional hazards predicted development of PD-MCI based on baseline and time-varying Neuro-QoL reporting.ResultsHigher MoCA memory performance was associated with better Neuro-QoL-GC (β = 0.75, SE = 0.391, p = 0.05) and Neuro-QoL-EF (β = 0.81, SE = 0.36, p = 0.02) at baseline. There was a trend for baseline MoCA memory to predict the degree of subjective cognitive decline on the Neuro-QoL-EF (β = 0.70, SE = 0.42, p = 0.09). Baseline depression and anticholinergic use were associated with worsened Neuro-QoL-EF and Neuro-QoL-GC. Increasing subjective cognitive complaints in Neuro-QoL-EF were associated with development of PD-MCI over 3 years of follow-up (HR = 0.95, CI = 0.90–1.0, p = 0.039).ConclusionsObjective memory impairment may be a stronger predictor than executive or visuospatial dysfunction for the presence of subjective cognitive complaints in early PD.     

Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: A national register-based study

AimUse of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD.MethodWe identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007.ResultsAll-cause mortality was significantly higher with the use of most groups of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04−1.36; Control HR = 1.77, 95% CI = 1.64−1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.99−1.38; Control HR = 1.39, 95% CI = 1.29−1.51; benzodiazepine-like drugs, PD HR = 1.33, 95% CI = 1.11−1.59; Control HR = 1.27, 95% CI = 1.18−1.37; first-generation antipsychotics, PD HR = 1.89, 95% CI = 1.42−2.53; Control HR = 2.12, 95% CI = 1.82−2.47; second-generation antipsychotics, PD HR = 1.46, 95% CI = 1.20−1.76; Control HR = 2.00, 95% CI 1.66−2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups.ConclusionsThe use of psychotropic medication in the elderly is associated with increased mortality, independent of concurrent neurodegeneration due to PD. Confounding by indication may partly explain the higher hazard ratios in medicated controls compared with medicated PD patients. Our findings indicate that neurodegeneration should not be a separate contraindication per se for the use of psychotropic drug in patients with PD, but its use should be based on careful clinical evaluation and follow-up.     

Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease

BackgroundLongitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD.MethodsProspective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied.Results97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5–34.1; p = 0.015) and dementia (OR 7.03, CI 2.39–25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for “time to cognitive impairment” (HR 7.67; CI 3.47–16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting “time to mild cognitive impairment” was significant (p = 0.0295).ConclusionsHippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.     

Investigation on sleep and mental health of patients with Parkinson's disease during the Coronavirus disease 2019 pandemic

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD).MethodsWe conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients.ResultsCompared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003).ConclusionThe findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson’s disease patients

IntroductionImpulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients.MethodsWe conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped.ResultsMultivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03–4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01–1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03–4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05–4.18, p = 0.035) were independently associated with ICD.ConclusionDRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.     

Excessive daytime sleepiness in Parkinson's disease: A systematic review and meta-analysis

ObjectiveTo provide a robust estimate of the prevalence of excessive daytime sleepiness (EDS) and its clinical correlates in patients with Parkinson's disease (PD).MethodWe searched the PubMed and Embase databases for studies investigating the prevalence and clinical correlates of EDS from inception to March 01, 2020. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Random-effects models were set to pool the risk estimates. Sensitivity analyses were performed to evaluate the stability of the outcomes.ResultsAfter screening 1367 titles and abstracts, 59 studies involving 12,439 participants were included in the systematic review and meta-analysis. The pooled prevalence of EDS in PD was 35.1%, which was higher in South America, North America, Europe, and Australia than that in Asia. Compared to patients without EDS, patients with EDS had higher effect size on disease duration (0.76 years; 95% CI: 0.16–1.37, I² = 68.8%), Hoehn and Yahr (HY) stage (0.23 grade; 95% CI: 0.11–0.34, I² = 69.1%), Unified PD Rating Scale (UPDRS)-III (3.02 points; 95% CI: 1.53–4.51, I²: 61.2%), levodopa equivalent daily dose (LEDD) (141.46 mg; 95% CI: 64.17–218.77, I² = 86.1%), depression symptoms (Hedges’ g = 0.35; 95% CI: 0.15–0.55, I² = 72.0%) and male sex (OR = 1.50; 95% CI: 1.30–1.72, I² = 0).ConclusionOur results showed that approximately one-third of patients with PD had EDS, which may be associated with the severity of the disease, depression, and male sex, or a combination of neurodegeneration and medication.     

Motor dual-tasking deficits predict falls in Parkinson's disease: A prospective study

IntroductionFalls severely affect lives of Parkinson's disease (PD) patients. Cognitive impairment including dual-tasking deficits contribute to fall risk in PD. However, types of dual-tasking deficits preceding falls in PD are still unclear.MethodsWalking velocities during box-checking and subtracting serial 7s were assessed twice a year in 40 PD patients over 2.8 ± 1.0 years. Fourteen patients reported a fall within this period (4 excluded fallers already reported falls at baseline). Their dual-task costs (DTC; mean ± standard deviation) 4.2 ± 2.2 months before the first fall were compared with 22 patients never reporting falls. ROC analyses and logistic regressions accounting for DTC, UPDRS-III and disease duration were used for faller classification and prediction.ResultsOnly walking/box-checking predicted fallers. Fallers showed higher DTC for walking while box-checking, p = 0.029, but not for box-checking while walking, p = 0.178 (combined motor DTC, p = 0.022), than non-fallers. Combined motor DTC classified fallers and non-fallers (area under curve: 0.75; 95% confidence interval, CI: 0.60–0.91) with 71.4% sensitivity (95%CI: 41.9%–91.6%) and 77.3% specificity (54.6%–92.2%), and significantly predicted future fallers (p = 0.023). Here, 20.4%-points higher combined motor DTC (i.e. the mean difference between fallers and non-fallers) was associated with a 2.6 (1.1–6.0) times higher odds to be a future faller.ConclusionMotor dual-tasking is a potentially valuable predictor of falls in PD, suggesting that avoiding dual task situations as well as specific motor dual-task training might help to prevent falls in PD. These findings and their therapeutic relevance need to be further validated in PD patients without fall history, in early PD stages, and with various motor-motor dual-task challenges.     

Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early?

IntroductionPsychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis.MethodologyIn this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics.ResultsCompared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP.ConclusionPresence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD.     

Pilomotor function is impaired in patients with Parkinson's disease: A study of the adrenergic axon-reflex response and autonomic functions

IntroductionAutonomic nervous system disturbances including sweating abnormalities and cardiovascular symptoms are frequent in Parkinson's disease (PD) and often precede motor involvement. Cholinergic vasomotor and sudomotor skin nerves are impaired in patients with PD even at early disease stages. We hypothesized that adrenergic pilomotor nerve function is similarly impaired in early PD and might constitute a novel diagnostic target.MethodsWe conducted a study in 12 PD patients (Hoehn&Yahr 1–2) and 12 healthy control subjects. Pilomotor function was evaluated after iontophoresis of phenylephrine on the dorsal forearm to elicit axon-reflex mediated pilomotor erection (goose bumps). Silicone impressions were obtained, scanned and quantified for pilomotor muscle impressions by number, area and axon-reflex spread. Vasomotor function was evaluated using laser Doppler flowmetry and sudomotor function via sympathetic skin response. Cardiac autonomic function was assessed via heart rate variability. Severity of autonomic symptoms was evaluated using the Scales for Outcomes in Parkinson's disease–Autonomic questionnaire.ResultsPilomotor response was reduced in PD patients compared to control subjects (impression number: 12.2 ± 8.2 vs. 16.5 ± 5.9, p < 0.05; impression area: 10.8 ± 2.2 mm² vs. 24.8 ± 3.1 mm², p < 0.01; axon-reflex spread: 89.0 ± 10.6 mm² vs. 185.9 ± 10.8 mm², p < 0.01) and correlated negatively with severity of autonomic symptoms (p < 0.01). Similarly, sudomotor (p < 0.01) and vasomotor (p < 0.05) but not cardiac autonomic (p = n.s.) function were reduced in PD patients versus control subjects.ConclusionPilomotor function is impaired in early stages of PD. Pilomotor axon-reflex assessment might be useful in the investigation of disease related pathology and supplement other clinical markers of autonomic neuropathy in PD.     

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease

BackgroundSleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders.Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD.MethodsClinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54).ResultsArousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387–95% CI 1.395–8.220, p = 0.007).ConclusionArousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.     

Parkinson's disease may worsen outcomes from coronavirus disease 2019 (COVID-19) pneumonia in hospitalized patients: A systematic review,meta-analysis,and meta-regression

BackgroundParkinson's Disease (PD) is among one of the common comorbidities in older patients. People with PD may be more vulnerable to severe pneumonia, due to the impairment of pulmonary function. Currently, the association between PD and COVID-19 is not yet established. This study aims to analyze the relationship between PD and in-hospital outcomes of COVID-19.Materials and methodsWe systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 25th, 2020. All articles published on COVID-19 and Parkinson's Disease were retrieved. The quality of the study was assessed using the Newcastle Ottawa Scale (NOS) tool for observational studies and Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional studies. Statistical analysis was done using Review Manager 5.4 software.ResultsA total of 12 studies with 103,874 COVID-19 patients were included in this meta-analysis. This meta-analysis showed that Parkinson's Disease was associated with poor in-hospital outcomes [[OR 2.64 (95% CI 1.75–3.99), p < 0.00001, I² = 81%] and its subgroup which comprised of severe COVID-19 [OR 2.61 (95% CI 1.98–3.43), p < 0.00001, I² = 0%] and mortality from COVID-19 [RR 2.63 (95% CI 1.50–4.60), p = 0.0007, I² = 91%]. Meta-regression showed that the association was influenced by age (p = 0.05), but not by gender (p = 0.46) and dementia (p = 0.23).ConclusionsExtra care and close monitoring should be provided to Parkinson's Disease patients to minimize the risk of infections, preventing the development of severe and mortality outcomes.     

Differential expression of gut miRNAs in idiopathic Parkinson's disease

ObjectiveIn the present work, we aimed to investigate the expression of microRNAs (miRNAs) in routine colonic biopsies obtained from patients with idiopathic Parkinson's disease (PD) and to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.MethodsPatients with PD (n = 13) and healthy controls (n = 17) were prospectively recruited to undergo routine colonic biopsies for cancer screening. Total RNA was extracted from the biopsy material and the expression of miRNAs was quantified by Illumina High-Throughput Sequencing.ResultsStatistical analysis revealed a significant submucosal enrichment of the miRNA hsa-miR-486–5p in colonic biopsies from PD patients compared to the control subjects. The expression of miR-486–5p correlated with age and disease severity as measured by the UPDRS and Hoehn & Yahr scale. miRNA gene target analysis identified 301 gene targets that are affected by miR-486–5p. A follow-up associated target identification and pathway enrichment analysis further determined their role in distinct biological processes in the enteric nervous system (ENS).InterpretationOur work demonstrates an enrichment of submucosal miR-486–5p in routine colonic biopsies from PD patients. Our results will support the examination of miR-486–5p as a PD biomarker and help to understand the significance of the miR-486–5p gene targets for PD onset and progression. In addition, our data will support the investigation of the molecular and cellular mechanisms of GI dysfunction in PD.