Impaired pain processing in Parkinson's disease and its relative association with the sense of smell

Background and purposeMany non-motor symptoms are associated with Parkinson's disease (PD). Of these, pain and olfactory disturbance tend to be common premotor symptoms. PD has been shown to exhibit abnormal central pain processing, although underlying mechanisms are not yet fully understood. In order to investigate this further, we assessed PD patients by specific Aδ stimulation with intra-epidermal needle electrode and determined olfactory function.MethodsForty-two patients (18 males and 24 females) with PD and 17 healthy control subjects (8 males and 9 females) were studied. A thin needle electrode was used to stimulate epidermal Aδ fibers, and somatosensory evoked potentials (SEPs) recorded at the vertex. Olfactory function was evaluated using the Odor Stick Identification Test for Japanese (OSIT-J) and its relationship with pain-related SEPs was investigated.ResultsThere were no significant differences in N1 latencies or P1 latencies although N1/P1 peak-to-peak amplitudes were significantly lower (p < 0.01) in PD patients than in control subjects. In PD patients, there were significant correlations between N1/P1 amplitudes and disease duration (r = ?0.35, p < 0.05), Hoehn-Yahr stage (r = ?0.38, p < 0.05) and UPDRS part III (r = ?0.42, p < 0.01). Furthermore, the OSIT-J scores correlated with SEP amplitude (r = 0.41, p < 0.01).ConclusionPain processing in PD patients was impaired under specific nociceptive stimulation of Aδ fibers and significant correlation with smell dysfunction was detected. We suggest that this mechanism may involve the limbic system during PD pathology.     

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.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.     

Association of low serum BDNF with depression in patients with Parkinson's disease

ObjectiveIncreasing evidence shows that brain-derived neurotrophic factor (BDNF) plays a critical role in the development of depression and the mechanisms of antidepressant. Parkinson disease (PD) is associated with depression and decreased BDNF. The aim of the present study was to examine the association of BDNF with depression in PD, which has not been investigated.MethodsWe recruited 96 PD patients with (n = 46) and without depression (n = 50) and 102 healthy controls and measured the serum BDNF levels in both groups. Zung Self-Rating Depression Scale (SDS) was administered for the severity of depression and Hoehn-Yahr staging scale for motor abilities in PD patients.ResultsSerum BDNF levels were significantly lower in PD patients than healthy controls (p < 0.01). Also serum BDNF levels were significantly decreased in PD patients with than without depression (p < 0.01). BDNF levels were negatively associated with SDS in both PD patients with and without depression (both p < 0.01). Multiple regression analysis confirmed that in either PD with or without depression group, BDNF was an independent contributor to SDS (both p < 0.05).ConclusionsOur findings suggest that decreased serum BDNF may be involved in the pathophysiology of depression in PD patients.     

Subjective memory decline in Parkinson's disease patients with and without fatigue

IntroductionPrevious studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet.MethodsOne-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of sample's features on results was controlled by logistic regression and Quade's rank analysis.ResultsTwenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (p_s < 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue.ConclusionFatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.     

Incidence and risk factors for stroke in patients with COVID-19 in the Philippines: An analysis of 10,881 cases

BackgroundWhile most large studies on the possible association of COVID-19 and stroke were done in high-income countries, only a few studies consisting of small sample populations have been done in low- to middle-income countries like the Philippines.ObjectivesTo determine the risk factors of stroke among hospitalized COVID19 patients in the Philippines; to determine the possible association between these risk factors and stroke among the same cohort; and to determine if there is an association between mortality and stroke in this same group.MethodologyWe obtained relevant clinical and neurological, including stroke data from the Philippine CORONA study, an observational study involving 10,881 patients with COVID-19 admitted in 37 referral hospitals from all over the Philippines.ResultsThe incidence of stroke among patients with COVID-19 was 3.4% (n = 367). There were more deaths among patients with stroke and COVID-19 than those without stroke and COVID-19 (42.2% vs 14.7%, p < 0.01). In addition, more patients with stroke were admitted in the ICU (43.3% vs 15.0%, p < 0.01) regardless of cause. Smoking (OR: 1.5, 95% CI: 1.3 to 1.7, p < 0.0001), hypertension (OR:1.75, 95% CI:1.53 to 1.97, p < 0.0001), presence of heart failure (OR: 1.4, 95% CI: 1.07 to 1.86, p = 0.01), presence of any neurologic co-morbidities (OR: 1.4, 95% CI:1.11 to 1.46, p = 0.004), and history of stroke (OR:2.3, 95% CI:1.82 to 2.97, p < 0.0001) had direct significant correlation with stroke; while being a health care worker (OR: 0.5, 95% CI: 0.33 to 0.70, p < 0.0004) had an inverse significant association with stroke.ConclusionCOVID-19 stroke patients in the Philippines have a higher mortality and ICU admission rates than patients with COVID-19 alone or COVID-19 stroke patients from developed countries. Our cohort has similar cardiovascular and metabolic risk factors to western patients with stroke, highlighting that COVID-19 may only have a small contribution to stroke incidence.     

Swallowing disturbances in Parkinson's disease: A multivariate analysis of contributing factors

BackgroundSwallowing disturbances are an important issue in Parkinson's disease (PD) as several studies have shown that they are associated with increased risk of aspiration pneumonia and mortality. Information about factors related to swallowing disturbances, such as disease duration, age at assessment and concomitant dementia, is limited and would be useful for their management.MethodsAll consecutive PD out-patients evaluated at a movement disorders clinic over a 7-year period (2007–2014), were included in the present retrospective study. Presence of symptomatic swallowing disturbances was assessed using the specific item of the Non Motor Symptom Questionnaire.ResultsIn the whole PD population (N = 6462), prevalence of symptomatic swallowing disturbances was 11.7% (95%CI, 10.9–12.5). Multivariable logistic regression analysis (adjusted for education) disclosed a significant interaction between disease duration and gender (P = 0.009). In both gender strata, swallowing disturbances were significantly associated with longer disease duration and dementia (P < 0.001 for all). A significant effect for age at assessment was also found in male patients. In non-demented patients, swallowing disturbances were associated with male gender, age and disease duration (P < 0.02 for all). In demented patients an association was found only with male gender (P = 0.018) and disease duration (P < 0.001).ConclusionsGender, age, disease duration and dementia all seem to contribute to the occurrence of swallowing disturbances independently. However, the role played by these factors in sub-groups of patients stratified by gender and concomitant dementia suggests that swallowing disturbances are likely related to different neuro-degenerative patterns within the brain. The underlying mechanisms deserve further investigation.     

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.     

Parkinson's disease patients first treated at age 75 years or older: A comparative study

BackgroundParkinson's disease (PD) first diagnosed at older age reportedly has different clinical characteristics and survival rates than when it is first diagnosed at younger age. We compared these features among PD patients who initiated anti-parkinsonian drugs at age 75–85 years (elderly) with those who started treatment at age 50–74 years (younger).MethodsWe used a population-based cohort of 4449 incident cases of PD patients aged 50–85 at treatment initiation, based on a pharmacy registry of Maccabi Health Maintenance Organization, with definite/probable/possible certainty of having PD. Mean follow-up was 3.9 ± 2.6 years. The two age groups were compared for time/risk to levodopa and to death, using Kaplan–Meier curves and Cox regression. Gender-specific standardized mortality rates (SMRs) accounting for Israeli death rates were also compared.ResultsOne-half of the entire cohort (n = 2148) were elderly (>75 years) and more likely to be given levodopa (Hazard Rate (HR) = 1.48, P < 0.05), had a significantly higher frequency of comorbidities (e.g., heart disease, hypertension and cancer), and had a 3-fold increased risk to die (HR = 2.97, P < 0.05) within the same follow-up time as the youngers. Accounting for the general Israeli population death rates, female PD patients had a significantly lower risk to die compared to males especially females who were elderly at treatment initiation (SMR = 1.53 for females vs. 1.73 for males, P < 0.05).ConclusionsPD patients first diagnosed and treated at >74 years of age comprise a unique cluster for inclusion into drugs studies, mortality risk analyses and for projection of disease burden.     

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China

BackgroundThe impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinson's disease (PD) in the Chinese population are largely unknown.ObjectivesTo study the impact of NMS on the HRQoL in Chinese PD patients.MethodsA total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinson's disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD.ResultsThe mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (r_s = 0.71, P < 0.01), sleep/fatigue domain (r_s = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (r_s = 0.55, P < 0.01), attention/memory (r_s = 0.42, P < 0.01), gastrointestinal (r_s = 0.44, P < 0.01) and Miscellany domains (r_s = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (r_s = 0.71, P < 0.01), emotional well-being (r_s = 0.62, P < 0.01), cognitions (r_s = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (r_s = 0.45, P < 0.01), activities of daily living (r_s = 0.43, P < 0.01), stigma (r_s = 0.42, P < 0.01), communication (r_s = 0.47, P < 0.01), bodily discomfort (r_s = 0.46, P < 0.01) and the total score of NMSS. Female, H–Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients.ConclusionsNMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.     

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention

IntroductionParkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort.MethodsRecently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition.ResultsBaseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = −2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = −0.4, p < 0.01).ConclusionsPD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL.     

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.     

Motor and non-motor symptoms of 1453 patients with Parkinson's disease: Prevalence and risks

PurposeWe examined the prevalence and risk of clinical symptoms in a large number of Japanese patients with Parkinson's disease (PD) (n = 1453; 650 males).MethodsEvents were analyzed using Kaplan–Meier survival curves, logistic regression, and Cox proportional-hazards models.ResultsThe mean age (SD) was 67.7 (10.0), age of onset was 58.0 (11.5), and disease duration was 9.7 (6.6) years. The mean modified Hoehn and Yahr stage was 2.8 (1.2). Most patients (88.9%) received levodopa (547.7 (257.6) mg/day). A large proportion (81.3%) received dopamine agonists (136.2 (140.7) mg/day). About 23.4% received pain treatment 6.9 (5.1) years after the onset; females (p < 0.05) and patients with late-onset PD (≥60 years, p < 0.001) were more likely to be affected. About 44.7% of patients had wearing-off 7.5 (4.7) years after the onset, and it was more common in females (p < 0.001) and patients with early-onset PD (p < 0.001). Camptocormia was found in 9.5% of patients 8.1 (6.2) years after the onset, and it was more common in females (p < 0.05) and patients with late-onset PD (p < 0.05). About 28.6% of patients developed psychosis 9.0 (5.4) years after the onset, and it was more likely to occur in patients with late-onset PD (p < 0.001). Late-onset PD and cerebrovascular disease were also associated with increased risk of pneumonia.ConclusionsConsidering that very few studies have assessed numerous clinical symptoms in the same report, these data provide a useful reference for the clinical course of PD.     

Subthalamic and red nucleus volumes in patients with Parkinson’s disease: Do they change with disease progression?

ObjectiveTo examine a possible correlation between disease progression and the volumes of the subthalamic nucleus (STN) and red nucleus (RN) in patients with Parkinson disease (PD).MethodsTwelve patients with PD (mean time since diagnosis 10.8 ± 2.9 years) and age-matched 12 normal control subjects were enrolled. The volumes of the STN and RN were measured using 3-dimensional volume reconstructions of stereotactic magnetic resonance images.ResultsThe PD and control groups were similar with regard to age and gender. The STN volume was 0.13 ± 0.01 cm³ (mean ± SD) in PD patients and 0.27 ± 0.01 cm³ in controls (P < .001). The RN volume was 0.31 ± 0.02 cm³ in PD patients and 0.21 ± 0.02 cm³ in controls (P = .002). Positive correlations of RN volume with time since diagnosis (P = .004) and disease stage (P = .01) were observed. On average, the STN volumes were 48% smaller and RN volumes 32% larger in PD patients than in control subjects; the volumes of the two nuclei were negatively correlated (r = −0.46; P = .03).ConclusionsOur results suggest that advanced disease stage and longer disease duration are associated with increased RN volume. STN volume was significantly smaller in Parkinson group. These findings may be useful in estimating disease status and rate of progression, and may also have implications for surgical treatment. Larger studies are needed to validate these results and determine their usefulness.     

Remote smartphone gait monitoring and fall prediction in Parkinson’s disease during the COVID-19 lockdown

Background

Falls could be serious events in Parkinson’s disease (PD). Patient remote monitoring strategies are on the raise and may be an additional aid in identifying patients who are at risk of falling. The aim of the study was to evaluate if balance and timed-up-and-go data obtained by a smartphone application during COVID-19 lockdown were able to predict falls in PD patients.

Methods

A cohort of PD patients were monitored for 4 weeks during the COVID-19 lockdown with an application measuring static balance and timed-up-and-go test. The main outcome was the occurrence of falls (UPDRS-II item 13) during the observation period.

Results

Thirty-three patients completed the study, and 4 (12%) reported falls in the observation period. The rate of falls was reduced with respect to patient previous falls history (24%). The stand-up time and the mediolateral sway, acquired through the application, differed between “fallers” and “non-fallers” and related to the occurrence of new falls (OR 1.7 and 1.6 respectively, p?<?0.05), together with previous falling (OR 7.5, p?<?0.01). In a multivariate model, the stand-up time and the history of falling independently related to the outcome (p?<?0.01).

Conclusions

Our study provides new data on falls in Parkinson’s disease during the lockdown. The reduction of falling events and the relationship with the stand-up time might suggest that a different quality of falls occurs when patient is forced to stay home — hence, clinicians should point their attention also on monitoring patients’ sit-to-stand body transition other than more acknowledged features based on step quality.

     

Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension,stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease

BackgroundEspecially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD.MethodsBased on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated.ResultsPD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02).After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD.ConclusionClear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.     

Sex,Food and Threat: Startling Changes after Subthalamic Stimulation in Parkinson's Disease

BackgroundChanges in motivational processing may play a role in weight gain and other non-motor side effects in Parkinson's disease (PD) patients treated with deep brain stimulation of the subthalamic nucleus.Objective/hypothesisWe aimed to assess changes in aversive and appetitive motivational activation using modulation of the acoustic blink reflex (ABR) by rewarding and aversive stimuli.MethodsABR elicited during the viewing of erotic, food, aversive and neutral pictures was recorded in 11 off-medicated patients with the subthalamic stimulation switched ON and OFF, and in 11 control subjects.ResultsABR to erotic stimuli was larger in patients in the ON compared to the OFF condition and controls (P < 0.01). Aversive stimuli caused a larger increase in the ABR in patients with the ON condition than in controls (P < 0.05). Additionally, we found a negative correlation of the ABR magnitude to food pictures in the ON condition with weight gain following subthalamic stimulation (P < 0.01, after adjustment to OFF condition).ConclusionsOur results suggest that subthalamic stimulation affects motivational processing. Subthalamic stimulation may disturb appetitive engagement by erotic cues and increase aversive activation in PD patients. Additionally, postoperative weight gain may be related to changes in the processing of food cues due to subthalamic stimulation.     

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.     

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors

BackgroundNocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone.ObjectivesTo quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores.MethodsNocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy.ResultsPD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed.ConclusionOur study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.     

Oropharyngeal freezing and its relation to dysphagia – An analogy to freezing of gait

IntroductionThe pathophysiology of dysphagia in Parkinson's disease (PD) is heterogeneous and poorly understood at present. This study investigated the phenotypes, prevalence and pathophysiology of oropharyngeal freezing (OPF) in PD and its relation to dysphagia.MethodsIn a prospective study, 50 PD patients were systematically screened for OPF using flexible endoscopic evaluation of swallowing (FEES). In addition, FEES-videos of 50 patients with post-stroke dysphagia and 50 healthy subjects were retrospectively evaluated as control groups. In PD patients freezing was assessed with the “freezing of gait (FoG) questionnaire” and the relationship between OPF and FoG was analyzed.ResultsIn analogy to FoG, signs for OPF presented as either temporarily missing or delayed swallowing reflex in combination with freezing associated movement abnormalities e.g. festination, trembling, or akinesia. Seventeen PD patients (34%) showed considerable signs for OPF (15 cases of festination, 3 cases of trembling, 3 cases of akinesia). In the patients with post-stroke dysphagia, OPF was detected in 2 patients (4%). The healthy subjects showed no signs for OPF. The distribution of OPF differed significantly between the investigated groups (p < 0.01). PD patients with signs for OPF scored significantly higher in the FoG-questionnaire (12.69 ± 6.37) compared to patients without OPF (7.29 ± 5.17; p < 0.01).ConclusionSwallowing in PD patients can be impaired by OPF. We suggest that OPF and FoG share common pathophysiologic mechanisms based on their association and similar semiologies.