Mean Parkinson's Disease Duration Research Articles

Real-World Experiences of Parkinson's Disease OFF Time and Role of Demographics.

OFF periods are episodes when Parkinson's disease (PD) medications work suboptimally, with symptoms returning and impacting quality of life. We aimed to characterize OFF periods using patient-reported frequency, severity, and duration, as well as determine these characteristics' associations with demographics. A retrospective cohort study using Fox Insight Data Exploration Network (Fox DEN) database was conducted. Eligible patients had PD and were >18 years. The experience of OFF periods was characterized by frequency (number of episodes/day), duration (duration/episode), and severity (impact on activities). Significance level was Bonferroni-corrected for multivariate analyses. From a population of 6,757 persons with PD, 88% were non-Hispanic Whites (mean age: 66 ± 8.8 years); 52.7% were males versus 47.3% females; mean PD duration was 5.7 ± 5.2; and 51% experienced OFF periods. Subsequent analyses were limited to non-Hispanic Whites, as they constituted a large majority of the participants and were the subgroup that had the sample size to derive reliable inferences. The analyses showed that 67% experienced 1-2 episodes/day, 90% experienced >15-minute episodes, and 55% reported slight-mild severity/episode. Lower age was associated with a higher frequency (incidence rate ratio [IRR]: 0.992; P<0.001) and severity (odds ratio [OR]: 0.985; P=0.001) of OFF episodes. Income of <$35,000 was associated with 15.1% more episodes/day (IRR: 1.15, p<0.001) and 66.5% higher odds of a severe episode (OR: 1.66; P<0.001). Females experienced 7.5% more episodes compared to males (IRR: 1.075; P=0.003). Longer PD duration was associated with 1.3% more episodes/day (IRR: 1.013; P<0.001) and 10% higher odds of a severe episode (OR: 1.10; P<0.001). Lower age, income <$35,000, longer PD duration, female gender, and being unemployed are associated with a higher frequency and severity of OFF periods with no associations for duration/episode among non-Hispanic Whites with PD. In time-constrained clinic environments, clinicians should tailor OFF periods management counseling to vulnerable demographic groups to enhance care delivery.(J Patient Cent Res Rev. 2024;11:8-17.).

Morbidity and severity of COVID-19 in patients with Parkinson's disease treated with amantadine - A multicenter, retrospective, observational study

BackgroundAfter more than 2 years of the pandemic, effective treatment for COVID-19 is still under research. In recent months, publications hypothesized amantadine's potential beneficial effect on SARS-CoV-2 infection. ObjectiveTo compare the groups of Parkinson's Disease (PD) patients who were administered amantadine chronically and those who did not take this medication in the context of the incidence and severity of COVID-19 infection. MethodsAn observational, retrospective, multicenter cohort study was conducted among consecutive patients with idiopathic PD. The structured questionnaires were completed during the patient's follow-up visits at the Outpatient Clinic or during hospitalization. The questionnaire included the following informations: patient's age, duration of PD, Hoehn-Yahr (H–Y) stage, comorbidities, medications, COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) swab test for SARS-CoV-2 with specified symptoms and their severity (home or hospital treatment). The vaccination status was verified as well. ResultsFive hundred fifty-two (n = 552) patients participated in the study - 329 men (60%). The mean H–Y stage was 2.44 (range: 1–4) and the mean duration of PD was 9.6 years (range: 1–34). One hundred four subjects (19%) had confirmed COVID-19 infection. Subjects over 50 years of age had a significantly lower incidence of COVID-19 (17% vs 38%, p = 0.0001) with difference also in mean H–Y stage (2.27 vs 2.49; p = 0.011) and disease duration (8.4 vs 9.9 years, p = 0.007). There were no differences between patients with and without co-morbidities. In the whole analyzed group 219 (40%) subjects were treated with amantadine. Comparing COVID-19 positive and negative patients, amantadine was used by 48/104 (46%) and 171/448 (38%) respectively. 22% of patients on amantadine vs. 17% of patients without amantadine developed COVID-19. These differences were not significant. There were no differences in morbidity and severity of COVID-19 between amantadine users and non-users as well. ConclusionsCOVID-19 was less common in older (>50) with longer duration and more advanced patients. Amantadine did not affect the risk of developing COVID-19 or the severity of infection.

Long-term motor outcomes of deep brain stimulation of the globus pallidus interna in Parkinson's disease patients: Five-year follow-up

BackgroundDeep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied. ObjectiveWe investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS. MethodsWe retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed. ResultsForty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04–1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39–17.89; p = 0.014, respectively). ConclusionsGPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients.

Neuropsychiatric Features, Health-Related Quality of Life, and Caregiver Burden in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease and significantly impacts patients and their caregivers. The current study aims at recognizing its neuropsychiatric symptoms, its impact on the health-related quality of life (HRQOL) of the patients, and the caregiver burden in a middle- to-low-income country. We conducted a cross-sectional survey of 73 idiopathic Parkinson's disease (IPD) patients and their caregivers from January 2021 to June 2021. Neuropsychiatric Inventory (NPI-12) and Parkinson's disease questionnaire (PDQ-39) were used to assess patients' symptoms and HRQOL, respectively. We used the Zarit caregiver burden interview (ZBI) and Hamilton depression scale (Ham-D) for the caregiver's burden assessment. Of the 73 patients, 43 (59%) were men, and 30 (41%) were women. Their mean age was 60.25 years (± 11.1), and the mean duration of PD was 6.4 years (± 3.4). Eighty-six percent of the patients reported having one or more neuropsychiatric symptoms. HRQOL, as indicated by PDQ-39, correlated most significantly with H and Y staging (r = 0.680, P < 0.001) of the disease. Sixty-eight percent of the caregivers felt a disease burden, and 55% had depression. On regression analysis, NPI total score on caregiver burden (beta = 0.883, P < 0.001, confidence interval [CI] of 1.087 to 1.400,) and H and Y staging on depression (beta = 0.772, P < 0.001, [CI of 0.629 to 0.934) were having the most decisive impact. Our study showed the presence of frequent neuropsychiatric symptoms in PD patients. It has a detrimental effect on the quality of life of patients and results in a significant increase in caregiver burden and depression among them.

Thalamic Dorsomedial Nucleus Free Water Correlates with Cognitive Decline in Parkinson's Disease.

Brain diffusion tensor imaging (DTI) has been shown to reflect cognitive changes in early Parkinson's disease (PD) but the diffusion-based measure free water (FW) has not been previously assessed. To assess if FW in the thalamic nuclei primarily involved with cognition (ie, the dorsomedial [DMN] and anterior [AN] nuclei), the nucleus basalis of Meynert (nbM), and the hippocampus correlates with and is associated with longitudinal cognitive decline and distinguishes cognitive status at baseline in early PD. Also, to explore how FW compares with conventional DTI, FW-corrected DTI, and volumetric assessments for these outcomes. Imaging data and Montreal Cognitive Assessment (MoCA) scores from the Parkinson's Progression Markers Initiative database were analyzed using partial correlations and ANCOVA. Primary outcome multiple comparisons were corrected for false discovery rate (q value). Thalamic DMN FW changes over 1year correlated with MoCA changes over both 1 and 3 years (partial correlations -0.222, q = 0.040, n = 130; and - 0.229, q = 0.040, n = 123, respectively; mean PD duration at baseline = 6.85months). NbM FW changes over 1 year only correlated with MoCA changes over 3 years (-0.222, q = 0.040). Baseline hippocampal FW was associated with cognitive impairment at 3 years (q = 0.040) and baseline nbM FW distinguished PD-normal cognition (MoCA ≥26) from PD-cognitive impairment (MoCA ≤25), (q = 0.008). The exploratory comparisons showed FW to be the most robust assessment modality for all outcomes. Thalamic DMN FW is a promising cognition progression biomarker in early PD that may assist in identifying cognition protective therapies in clinical trials. FW is a robust assessment modality for these outcomes. © 2021 International Parkinson and Movement Disorder Society.

Exploratory pilot study of exogenous sustained-release melatonin on nocturia in Parkinson's disease.

Nocturia is one of the commonest non-motor symptoms in Parkinson's disease (PD). Nocturia has evolved from being understood as a symptom of urological disorders or neurogenic bladder dysfunction to being considered as a form of circadian dysregulation. Exogenous melatonin is known to help circadian function and can be an effective strategy for nocturia in PD. In this open-label, single-site, exploratory, phase 2 pilot study, adults with PD and nocturia underwent assessments using standardized questionnaires, urodynamics studies and a bladder scan. This was followed by completion of a frequency volume chart (FVC) and 2-week sleep diary. Sustained-release melatonin 2mg was then administered once-nightly for 6weeks. A repeat assessment using questionnaires, the FVC and sleep diary was performed whilst on treatment with melatonin. Companion or bed partners filled in sleep questionnaires to assess their sleep during the intervention. Twenty patients (12 males; mean age 68.2 [SD=7.8] years; mean PD duration 8.0 [±5.5] years) with PD reporting nocturia were included. Administration of melatonin was associated with a significant reduction in the primary outcome bother related to nocturia measured using the International Consultation on Incontinence Questionnaire Nocturia (ICIQ-N) (p=0.01), number of episodes of nocturia per night (p=0.013) and average urine volume voided at night (p=0.013). No serious adverse events were reported. No significant improvement was noted in bed partner sleep scores. In this preliminary open-label study, administration of sustained-release melatonin 2mg was found to be safe for clinical use and was associated with significant improvements in night-time frequency and nocturnal voided volumes in PD patients.

Long term follow-up in advanced Parkinson's disease treated with DBS of the subthalamic nucleus.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been an approved treatment for PD for more than 30years, but few data are available regarding its long-term effectiveness. The aim of this study is to evaluate patients' outcome, both from a motor and non-motor perspective, 9 to 14years after DBS implantation. We have investigated patients with advanced PD and treated with STN-DBS, in relation to key clinical features of PD. 18 patients were assessed both retrospectively and prospectively. They underwent motor examination, neuropsychological evaluation and questionnaires on the quality of life, preoperatively, as well as 1, 9 and 14years after DBS surgery. All patients were implanted with STN-DBS at San Raffaele Hospital between 2004 and 2010. 13 males and five females underwent DBS implantation with a mean PD duration of 11years. Stimulation significantly improved med-off/stim-on condition up to 9years, compared to the preoperative off state, and med-on/stim-on condition at 14years, compared to med-on/stim-off state. Long term improvement specifically involved tremor and rigidity, as well as dopaminergic daily dose. At the same time, STN-DBS had no long-lasting effect on axial symptoms and cognitive functions. STN-DBS remains an effective therapy for advanced PD, also over the years. Despite the underlying progression of the disease, this treatment extends the period in which the overall quality of life is still acceptable.

Associations Between Fluctuations in Daytime Sleepiness and Motor and Non-Motor Symptoms in Parkinson's Disease.

ABSTRACTBackgroundNon‐motor fluctuations are a major concern in Parkinson's disease (PD), and they have been categorized into neuropsychiatric, autonomic and sensory fluctuations. However, this categorization does not include sleep and sleep‐related features, and the association between daytime sleepiness and other motor and/or non‐motor fluctuations in PD remains to be elucidated.ObjectiveTo investigate the relationship between daytime sleepiness and other non‐motor and motor fluctuations in people with PD.MethodsA three‐day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and 6 days of accelerometer (Parkinson's KinetiGraph™; PKG™) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2 years). Participants were categorized as motor fluctuators or non‐fluctuators according to the UPDRS part IV and/or the presence of motor and non‐motor fluctuations.ResultsFifty‐two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non‐fluctuators (n = 24). Stronger positive within‐individual correlations were found among fluctuators in comparison to non‐fluctuators. In general, PKG data did not correlate with diary data.ConclusionEpisodes of daytime sleepiness, as reported by home diaries, were associated with other self‐reported non‐motor and motor fluctuations, but were not supported by PKG data.

Pharmacokinetics of Inhaled Levodopa Administered With Oral Carbidopa in the Fed State in Patients With Parkinson's Disease

PurposeLevodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur unpredictably, partly due to the pharmacokinetic (PK) variability of oral LD, resulting from gastrointestinal dysfunction and from the effects of food on absorption. CVT-301 is a levodopa inhalation powder for the treatment of OFF period symptoms in patients on oral dopa-decarboxylase inhibitor/LD. PK and safety profiles of single dose CVT-301, administered with oral carbidopa (CD) and oral CD/LD, were examined in patients with Parkinson's disease in the fed state. MethodsEligible patients were aged 30–85 years, with a clinical diagnosis of Parkinson's disease and a body mass index of 18–32 kg/m2, and were receiving treatment with a stable regimen that included oral CD/LD (25/100 mg) (total LD, ≤800 mg/d). A high-fat/protein meal was eaten 4–5 h after the administration of the morning oral CD/LD dose. Blood samples for predose PK analysis were obtained after the meal, followed by a single inhaled dose of CVT-301 84 mg (+25 mg of oral CD) or oral CD/LD (25/100 mg) or vice versa in 2 dosing periods in a crossover design. Blood was sampled at 0, 5, 10, 15, 30, and 45 min and at 1, 1.5, 2, 3, and 4 h postdose. Tolerability assessments included treatment-emergent adverse events. FindingsTwenty-three patients were enrolled (65.2% male; 87.0% white; mean age, 69.3 years; mean body mass index, 26.9 kg/m2; mean Parkinson's disease duration, 8.2 years; mean baseline LD dosage, 460.9 mg/d; 73.9% at Hoehn and Yahr stage <2.5). PK analyses were based on LD concentrations without baseline adjustment. Median Tmax values with CVT-301 and oral CD/LD were 15 and 120 min (P < 0.001). Cmax with CVT-301 was lower than with oral CD/LD (590.3 vs 844.3 ng/mL). C10min and C30min values with CVT-301 were approximately twice those with CD/LD (522.9 and 531.5 ng/mL vs 247.3 and 300.9 ng/mL, respectively). %CV for C5min to Cmax with CVT-301 was lower than that with oral CD/LD. The most common treatment-emergent adverse event was cough (CVT-301, 7 patients [30.4%]; oral CD/LD, 1 patient [4.5%]). ImplicationsPK properties showed that CVT-301 was more rapidly absorbed, with higher plasma LD concentrations in the first 45 min, and demonstrated lower interpatient variability, than was oral CD/LD in the fed condition. The study findings suggest that CVT-301 can be used without regard to food intake. ClinicalTrials.gov identifier: NCT03887884.

Factors Associated With Postoperative Confusion and Prolonged Hospital Stay Following Deep Brain Stimulation Surgery for Parkinson Disease.

Several patient and disease characteristics are thought to influence DBS outcomes; however, most previous studies have focused on long-term outcomes with only a few addressing immediate postoperative course. To evaluate predictors of immediate outcomes (postoperative confusion and length of postoperative hospitalization) following deep brain stimulation surgery (DBS) in Parkinson disease (PD) patients. We conducted a retrospective study of PD patients who underwent DBS at our institution from 2006 to 2011. We computed the proportion of patients with postoperative confusion and those with postoperative hospitalization longer than 2 d. To look for associations, Fisher's exact tests were used for categorical predictors and logistic regression for continuous predictors. We identified 130 patients [71% male, mean age: 63±9.1, mean PD duration: 10.7±5.1]. There were 7 cases of postoperative confusion and 19 of prolonged postoperative hospitalization. Of the 48 patients with tremors, none had postoperative confusion, whereas 10.1% of patients without tremors had confusion (P=.0425). Also, 10.2% of patients with preoperative falls/balance-dysfunction had postoperative confusion, whereas only 1.6% of patients without falls/balance-dysfunction had postoperative confusion (P=.0575). For every one-unit increase in score on the preoperative on-UPDRS III/MDS-UPDRS III score, the odds of having postoperative confusion increased by 10% (P=.0420). The following factors were noninfluential: age, disease duration, dyskinesia, gait freezing, preoperative levodopa-equivalent dose, number of intraoperative microelectrode passes, and laterality/side of surgery. Absence of tremors and higher preoperative UPDRS III predicted postoperative confusion after DBS in PD patients. Clinicians' awareness of these predictors can guide their decision making regarding patient selection and surgical planning.

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.

Predictive Factors of Concerns about Falling in People with Parkinson's Disease: A 3-Year Longitudinal Study.

Introduction Fear of falling (FOF) is more common in people with Parkinson's disease (PD) than in healthy controls. It can lead to several negative consequences such as restrictions in everyday life. Moreover, FOF is a risk factor for future falls. Aim This study aimed to identify predictive factors of FOF (conceptualized as concerns about falling) after three years, with and without adjusting for concerns about falling at baseline, in people with PD. Methods This study included 151 participants (35% women) with PD. At baseline, their mean (SD) age and PD duration were 68 (±9.0) and 9 (±6.1) years, respectively. The Falls Efficacy Scale-International (FES-I) was used as the dependent variable in multivariable linear regression analyses. Results The mean (SD) FES-I score increased from 28.1 (11.9) to 33.1 (14.0) three years later (p < 0.001). The strongest (according to the standardized regression coefficient, β) predictor of concerns about falling was walking difficulties (β = 0.378), followed by age (0.227), problems maintaining balance while dual tasking (0.172), and needing help in daily activities (0.171). When adjusting for baseline FES-I scores, the strongest predictive factor was problems maintaining balance while dual tasking (β = 0.161), which was followed by age (0.131) and female sex (0.105). Conclusions This study pinpoints several predictive factors of concerns about falling that are modifiable and which could be addressed in rehabilitation: perceived walking difficulties, having problems maintaining balance while dual tasking, and dependence on others in daily activities. The importance of dual tasking is a novel finding, which future studies need to confirm or refute. One should be aware of the fact that an increased age predicts concerns about falling with and without adjusting for baseline FES-I scores, whereas female sex predicts concerns about falling only when adjusting for baseline FES-I scores.

Philippine translation and validation of the Wearing-off Questionnaire-19

IntroductionThe 19-item Wearing-Off questionnaire is used as a self-administered questionnaire assessing wearing-off (WO) in Parkinson's disease (PD) patients. Thus, we aim to translate and validate the WOQ-19 into Filipino (FWOQ-19). MethodsWe translated the WOQ-19 questionnaire into Filipino and used it to assess WO among Filipino PD patients. The original WOQ-19 was translated into Filipino using forward and backward translation by independent bilingual translators. WO is present if the patients checked at least 2 symptoms in the WOQ-19. Baseline demographic data, disease duration and medication use were collected. Internal consistency was measured using Cronbach's alpha. The Unified Parkinson's Disease Rating Scale (UPDRS) part IV and WOQ-32 were correlated with FWOQ-19 through Pearson's correlation coefficient to assess construct validity. Results and discussionThe FWOQ-19 was answered by 46 patients. The mean age of the participants was 60.8 ± 10.0 years (range, 40–86 years). The mean duration of PD was 10.9 ± 3.1 years (range, 1–26 years). Majority (n = 38, 82%) of patients claimed that WO is predictable and only 2 of the patients claimed that WO is unpredictable. The rest of the patients (n = 6, 13%) said that they did not experience WO. The internal consistency of the FWOQ-19 is acceptable (Cronbach's alpha 0.7808). There is a high correlation between WOQ-32 and FWOQ-19 (r = 0.8191). The troublesome symptoms for the patients were tremor, insomnia, weakness and slowness. ConclusionThe FWOQ-19 is a valid assessment tool for detecting wearing-off among Filipino-speaking PD patients.

Predictors of dementia-free survival after bilateral subthalamic deep brain stimulation for Parkinson's disease.

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor complications and quality of life (QOL) in patients with Parkinson's disease (PD). However, it does not delay or prevent the occurrence of dementia. The deleterious effects of dementia on QOL and activities of daily living (ADL) underscore the importance of identifying predictors of dementia-free survival in PD patients considered for STN DBS. The baseline clinical and neuropsychological data and the occurrence of dementia recorded during the longitudinal follow-up of a cohort of patients with PD with at least 2 years follow-up after bilateral STN DBS, were reviewed. One hundred and sixteen patients operated between 1999 to 2014 satisfied the inclusion criteria. Their mean age was 56.5 (±10) years and the mean duration of PD at surgery was 11.2 (±4.2) years. During the 542 person-years of follow-up, 30 patients developed dementia. The mean dementia-free survival after surgery was 8.7 [95% confidence interval (CI): 7.8-9.6] years. In univariate analysis, the baseline factors of older age, longer disease duration, past history of depression or psychosis, freezing of gait in OFF phase, worse ADL scores in ON phase, lower levodopa response of the Unified Parkinson's Disease Rating Scale (UPDRS) III axial sub-scores, and poor performances in the Addenbrooke's Cognitive Examination and Wisconsin Card Sorting Test (WCST) were associated with a shorter dementia-free survival. Among these, only freezing of gait and poor performance in WCST were independent predictors. Presence of freezing of gait in the drug OFF state and executive dysfunction predict the occurrence of earlier dementia in PD patients who otherwise qualify for bilateral STN DBS.

Effect of Lee Silverman Voice Treatment (LSVT LOUD®) on swallowing and cough in Parkinson's disease: A pilot study

PurposeLee Silverman Voice Treatment (LSVT LOUD®) is an effective therapy for phonation in Parkinson's Disease (PD) but little is known about any additional spread of effects to swallowing and cough function. This pilot study examined the effect of LSVT LOUD on pharyngeal swallowing parameters and reflexive cough strength. MethodsTwenty participants (14 men, 6 women; mean 68years, SD3.5) with PD referred for LSVT LOUD with complaints of voice deterioration were recruited. Mean duration of PD was 6yrs., SD 3. Self-reported Eating Assessment Tool-10 scores ranging from 0 to 25 (normal<3). Prior to LSVT LOUD, 1-week post- and 6-months post-treatment, participants undertook a videofluoroscopic study of swallowing and aerodynamic measures of involuntary cough. ResultsAll participants completed the LSVT LOUD programme; 3 participants were lost to follow-up at 6-months. All participants made significant gains in average sound pressure level (dB SPL). Aspiration was not observed. Pharyngeal residue (p<0.05) and pharyngeal area at rest reduced (p<0.01) while maximal opening of pharyngoesophageal segment (PES) (p<0.05) and PES opening duration (p<0.05) significantly increased. There was a significant improvement in involuntary cough peak expiratory flow rate and peak expiratory flow rise time. All changes were maintained at 6-months. ConclusionLSVT LOUD demonstrates additional spread effects on pharyngoesophageal deglutitive function and involuntary cough effectiveness in people with mild PD referred with voice complaints. Consequently, LSVT LOUD has potential to provide additional benefits for swallowing safety and efficiency in this patient group.

Factors Contributing to Perceived Walking Difficulties in People with Parkinson's Disease.

While walking difficulties are common in people with Parkinson's disease (PD), little is known about factors that independently contribute to their perceived walking difficulties. To identify factors that independently contribute to perceived walking difficulties in people with PD. This study involved 243 (62% men) participants; their mean (min-max) age and PD duration were 70 (45-93) and 8 (1-43) years, respectively. A postal survey preceded a home visit that included observations, clinical tests, questions and questionnaires that were administered as a structured interview. Perceived walking difficulties (dependent variable) were assessed with the self-administered generic Walk-12 (Walk-12G, scored 0-42, higher = worse). Independent variables included personal (e.g., age and general self-efficacy) and social environmental factors (e.g., social support and living situation) as well as disease-related factors including motor (e.g., freezing of gait (FOG) and postural instability) and non-motor symptoms (e.g., fatigue and orthostatic hypotension). Linear multiple regression analysis was used to identify factors that independently contributed to perceived walking difficulties. Eight significant independent variables explained 56.3% of the variance in perceived walking difficulties. FOG was the strongest significant contributing factor to perceived walking difficulties, followed by general self-efficacy, fatigue, PD duration, lower extremity function, orthostatic hypotension, bradykinesia and postural instability. Motor and non-motor symptoms as well as personal factors (i.e., general self-efficacy) seem to be of importance for perceived walking difficulties in PD. These findings might nurture future interventions that address modifiable factors in order to enhance walking ability in people with PD.

STN DBS for Parkinson's disease: results from a series of ten consecutive patients implanted under general anaesthesia with intraoperative use of 3D fluoroscopy to control lead placement.

Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) is a recognised treatment for advanced Parkinson's disease (PD). We present our results of 10 consecutive patients implanted under general anaesthesia (GA) using intraoperative robotic three-dimensional (3D) fluoroscopy (Artis Zeego; Siemens, Erlangen, Germany). Ten patients (nine men, one woman) with a mean age of 57.6 (range, 41-67) years underwent surgery between October 2013 and January 2015. The mean duration of PD was 9.2 [1-10] year. The procedure was performed under GA: placement of the stereotactic frame, implantation of the electrodes (Lead 3389; Medtronic, Minnesota, MN, USA) and 3D intraoperative fluoroscopic control (Artis Zeego) with image fusion with the preoperative MRI scans. All patients were evaluated preoperatively and 6months postoperatively. The mean operative time was 240.1 (185-325) min. The mean Unified Parkinson's Disease Rating Scale (UPDRS) II OFF medication decreased from 23.9 preoperatively to 15.7 postoperatively. The mean OFF medication UPDRS III decreased from 41 to 11.6 and the UPDRS IV decreased from 10.6 to 7. The mean preoperative and postoperative L-Dopa doses were 1,178.5 and 696.5mg, respectively. Two complications were recorded: one episode of transient confusion (24h) and one internal pulse generator (IPG) infection. With improvement in preoperative magnetic resonance imaging (MRI) and the ability to control the position of the leads intraoperatively using Artis Zeego, we now perform this procedure under GA. Our results are comparable to others reported. The significant decrease in the duration of surgery could be associated with a reduced rate of complications (infection, loss of patient collaboration). However, this observation needs to be confirmed.

Nocturia in Patients With Parkinson's Disease.

Waking up from sleep more than once to pass urine, known as nocturia, is an important nonmotor symptom in Parkinson's disease (PD). Very little is known about the cause for nocturia. The aim of this work was to evaluate lower urinary tract (LUT) symptoms in patients with PD reporting nocturia using standardized validated questionnaires and bladder diaries and to assess the impact of nocturia on quality of life and sleep. Twenty-three consecutive patients with PD (17 males, 6 females; mean age: 68.5 years; range, 50-85) referred to a specialist uro-neurology clinic reporting nocturia according to the International Continence Society definition were included. Patients measured their daily fluid intake, urinary output per void, and recorded these with the timing of voids on a 3-day bladder diary. Standardized questionnaires were used to assess LUT symptoms (Urinary Symptom Profile, International Prostate Symptom Score, and Qualiveen Short Form) and sleep quality (Parkinson's Disease Sleep Scale). Mean duration of PD was 10.1 years, and mean severity on H & Y scale was 3.0 (range, 1.0-5.0). Median duration of LUT symptoms was 6.0 years. Mean night-time urinary frequency was 3.5 (range, 1.0-7.3), and mean nocturnal maximum voided volume was 242 mL. Mean Nocturnal Polyuria Index (NPi) was 0.4 (range, 0.13-0.75), and 13 patients (56.5%) had nocturnal polyuria (NPi > 0.33). Patients with nocturnal polyuria reported more-severe LUT symptoms that impacted quality of life and sleep. In this preliminary study, nocturnal polyuria seems to be common in patients with PD reporting nocturia and appears to affect quality of life and sleep, though this was not statistically significant. The bladder diary is an essential tool in the assessment of nocturia in patients with PD.

The timing of deep brain stimulation for Parkinson disease in the UK from 1997 to 2012.

Deep brain stimulation (DBS) for Parkinson disease (PD) has traditionally been reserved for the late stages of the disease. There is evidence that DBS is also effective if applied earlier in the disease course. Changes in the frequency of DBS procedures in the UK over a 15-year period were investigated. A retrospective review was performed of patient age and disease duration for DBS surgery for PD in UK neurosurgical units from 1997 to 2012 using departmental databases. The number of DBS procedures in the UK increased from three in 1997 to over 80 per year during this period. The mean age at the time of surgery (60 years) and the mean duration of PD at the time of DBS (11 years) remained unchanged over 15 years. The age and disease duration at which DBS is performed for PD in the UK has been static over a 15-year period and DBS appears to remain a therapy for PD applied late in its course. This may change in the light of clinical evidence suggesting a benefit for earlier DBS.

Baseline C-Reactive Protein Levels and Life Prognosis in Parkinson Disease.

BackgroundC-reactive protein (CRP) is a biomarker of inflammation, and high levels of CRP correlate with vascular death. Chronic inflammation is considered to be involved in neurodegeneration, although there is no evidence linking it with the process of neurodegenerative diseases.ObjectiveTo determine the role of baseline CRP levels in the prognosis of patients with Parkinson disease (PD).MethodsA cohort of 313 patients with a mean age of 69.1 and mean PD duration of 7.9 years was retrospectively followed for a mean observation time of 1,753 days. CRP was measured when patients were not diagnosed with any infections, and levels were repetitively measured to investigate a tendency of “regression to mean.” The primary outcome measure was a survival time from study enrollment to death.ResultsDuring the observation period 56 patients died. Baseline CRP was log-linearly associated with a risk of death in PD. Mean survival time was 3,149 (95% confidence interval; 3,009-3,289) days in patients with CRP ≤ 0.8mg/L (lower two thirds) and 2,620 (2,343-2,897) days in those with CRP > 0.8 mg/L (top third, p < 0.001, log-rank test). The adjusted hazard ratio (HR) per two-fold higher CRP concentration for all deaths was 1.29 (1.10-1.52), and after excluding PD-unrelated deaths, such as cancer or stroke, HR was 1.23 (1.01-1.49) (adjusted for age, sex, PD duration, modified Hohen-Yahr stages, MMSE scores, and serum albumin).ConclusionsBaseline CRP concentrations were associated with the risk of death and predicted life prognosis of patients with PD. The associations were independent from PD duration, PD severity, cognitive function, ages, and nutritional conditions, suggesting the possibility that subclinical chronic inflammation is associated with a neurodegenerative process in PD.