Search

BACKGROUND: Previous studies revealed an association between vascular comorbidities and obstructive sleep apnea (OSA) and the severity of motor and cognitive symptoms in Parkinson's disease (PD). However, there is a lack of studies assessing the entire spectrum of non‐motor symptoms (NMS). OBJECTIVE: To investigate the relationship between vascular comorbidities and NMS in PD patients. METHODS: Patients were assessed at baseline and 4 years later with the Non‐Motor Symptom Assessment Scale, Parkinson's Psychosis Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Apathy scale. After tetrachoric correlation matrix, we conducted linear regression models (adjusted for age, gender, disease duration, and UPDRS‐III) to investigate the relationship between vascular comorbidities and NMS. RESULTS: In 73 PD patients, (mean disease duration 7.1 [5.3]), 57% had hypertension, 44% body mass index >25, 44% elevated cholesterol, 15% diabetes mellitus, 15% OSA, 14% cigarette‐smoking history, 8% prior stroke, and 8% coronary disease. Cognition, psychotic symptoms, apathy, urinary function, and miscellaneous domains significantly worsened at the 4‐year follow‐up. OSA was significantly associated with higher severity of hallucinations/illusions at baseline and with a more severe deterioration of attention/memory, psychotic symptoms, and apathetic mood at the 4‐year follow‐up. At baseline, but not at follow‐up, hypertension was negatively associated with miscellaneous domain scores and coronary disease with autonomic function scores (gastrointestinal tract and urinary function domains). CONCLUSION: Among PD‐associated comorbidities, OSA was the main factor of decline. In addition to cognitive impairment, OSA might also potentially worsen psychotic symptoms and apathy. Treatment of OSA could be a strategy to improve these important NMS.

Background Parkinson's disease (PD) is multi-symptom disease with variable progression. Objectives We performed a longitudinal study to address the evolution of motor symptoms (MS) and non-motor symptoms (NMS), predictors of motor-, cognitive-, disability-, and health-related quality of life (HRQL) status and the relative usefullness of a battery of separate NMS scales (BSS) versus the Non-Motor Symptom Scale (NMSS). Methods Seventy-two patients were assessed at baseline and 4 years later with the NMSS and BSS. We assessed the following outcomes: cognition (Montreal Cognitive Assessment scale [MoCA]), disability (Unified Parkinson's Disease Rating Scale Part II [UPDRS II], Schwab and England [S&E]), motor dysfunction (Unified Parkinson's Disease Rating Scale Part III [UPDRS III], Hoehn and Yahr [HY]), and HRQL (EuroQol [EQ] EQ-vertical visual analogue scale [VAS] and EQ-Index). Statistical analysis included a comparison between scales scores at both time points and multivariate regression analysis to calculate the impact of each baseline symptom in outcomes. NMSS and BSS were introduced in separate models. Results NMSS Domain 4: perception/hallucinations, Parkinson's Psychosis Questionnaire, Apathy Scale, NMSS Domain 7: urinary, S&E, UPDRS II, HY, and MoCA scores worsened significantly. Dementia increased to a 4-year prevalence of 39.8%. In the multivariate model using BSS, cognitive state variation was significantly predicted by baseline HY, EQ-Index, and S&E. Using the NMSS, MoCA change was significantly associated with NMSS Domain 4: perceptions/hallucination score, cognitive status with UPDRS III score, HRQL with NMSS Domain 4: perception/hallucinations score, and S&E. Conclusion Our study suggests that NMS progress heterogeneously, BSS approach being more sensitive to change than NMSS. The multivariate analysis has shown that S&E and NMSS Domain 4: perception/hallucinations scores are the stronger predictors of HRQL and cognitive dysfunction variation, favoring NMSS over the BSS approach.

Introduction Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) prognosis depends on cognitive function evolution. Sleep disorders, as objectivated by polysomnography (PSG), are intimately connected with PD and DLB pathophysiology, but have seldomly been used to predict cognitive decline. Methods 20 DLB and 49 PD patients underwent one-night in-lab video-PSG. Sleep variables were defined, including REM sleep motor events, Tonic and phasic REM sleep muscular tone and RBD diagnosis. Cognitive state (assessed with the Global Deterioration Scale (GDS) was collected from case files for 6 months intervals, for a maximum period of 3.5 years or until death/drop-out.). The relation between PSG data at baseline and variation of GDS scores over time was tested with mixed linear regression analysis. Results GDS scores were higher in DLB, than in PD. We confirmed significant cognitive decline in both disorders, but no significant differences in progression between them. There were no significant interactions between PSG data and GDS variation for the entire group and DLB separately. In PD patients, there was a significant interaction between RBD diagnosis and tonic excessive muscular tone and GDS increase. Conclusion Our data suggests that PSG data can be useful in predicting cognitive decline in PD but not in DLB patients. In PD patients, an RBD diagnosis is predictive of cognitive deterioration, confirming the notion that this non-motor symptom relates to a malignant sub-type. Tonic excessive muscular activity, but not other RBD features, had predictive value in this group, pointing to a specific relation with the disease pathophysiology.

Background: Headache calendars are part of good clinical practice in headache clinics. However, patients’ compliance is rather variable. We aim to identify factors associated with poor compliance. Methods: Consecutive patients observed in follow-up visits of a tertiary headache center were divided into two groups; with a fullfilled calendar (Calendar compliers, CC) and without calendar (Calendar noncompliers, CNC). Incomplete / forgotten records were excluded. Demographic and clinical variables were compared, and CNC were asked the reasons for not filling the calendar. Results: From 93 patients (45.6±13.3 years, on average; 83 females), the majority with migraine (96.8%), 61.3% were CC. CNC were more likely to have medication overuse (34.5% vs. 12.3%, p=0.01) and had a tendency to be paid workers (79.3% vs. 52.6%, p=0.05) compared to CC. Most CC considered calendars useful to improve doctors and patients knowledge about headaches.Conclusions: Although these results need to be evaluated in other contexts, they suggest that patients with medication overuse have a more denial attitute towards headache records and may need additional reinforcement.

Introduction Sleep dysfunction is frequent in Dementia with Lewy Bodies (DLB), but polysomnographic (PSG) data is scarce. Our objectives were to: (1) compare PSG data between DLB patients and age normative values (NV), Parkinson's Disease (PD) and idiopathic REM sleep behavior disorder (iRBD) patients; (2) evaluate the relation between of OSA, Fluctuations and Hypersomnolence and PSG data. Methods We selected all consecutive patients with DLB, PD and iRBD that underwent video-PSG during a two year period. Clinical data was collected by file review. Video-PSG data included sleep structure, Apnea-Hypopnea Index (AHI), REM sleep atonia indexes and video file inspection of motor events (ME) during REM sleep. Results Subjects: In this study, 19 DLB, 51 PD and 20 iRBD patients participated. Of those, nine DLB (DLB-RBD) and 23 PD (PD-RBD) patients had RBD. Compared to NV, DLB patients had significantly lower sleep efficiency, total sleep time, and REM sleep duration and higher sleep latency, wake after sleep onset and N2 duration. There were no significant relations between PSG data and OSA, hypersomnolence or fluctuations. Sleep latency and AHI were significantly higher and lower, respectively, in DLB compared to PD patients. ME frequency was higher in iRBD. Conclusion DLB patients present significant sleep fragmentation and shortened total and REM sleep time. These changes were not related with OSA, fluctuations or hypersomnolence, suggesting a different pathophysiology. PSG data was similar in the three RBD groups, in accordance with a common neuropathological origin, except for an increase in RBD severity in patients with iRBD.

Aims: Inflammation impacts several acute and chronic diseases causing localized stress and cell death, releasing tissue-specific lipids into the circulation from inflamed cells and tissues. The plasma lipidome may be expected to reflect the type of inflammation. However, deep lipid profiles of major chronic inflammatory diseases have not been compared. Methods and Results: We compared the plasma lipidomes of patients suffering from two etiologically distinct chronic inflammatory diseases, atherosclerosis-related cardiovascular disease (CVD) including ischemic stroke (IS), and systemic lupus erythematosus (SLE), to each other and to age-matched controls. The controls had never suffered from any of these diseases. Plasma lipidomes were screened by a top-down shotgun MS-based analysis without liquid chromatographic separation. Lipid profiling of 596 lipids based on MS was performed on a cohort of 427 individuals. Machine learning classifiers based on the plasma lipidomes of patients suffering from CVD and SLE allowed clear distinction of these two chronic inflammatory diseases from each other. We demonstrate convincing evidence for the capability of lipidomics to separate the studied chronic and inflammatory diseases from controls based on independent validation test set classification performance (CVD vs control - Sensitivity: 0.90, Specificity: 0.98; IS vs control - Sensitivity: 1.0, Specificity: 1.0; SLE vs control – Sensitivity: 1, Specificity: 0.88) and from each other (SLE vs CVD ‒ Sensitivity: 0.91, Specificity: 1). Preliminary linear discriminant analysis plots using all data clearly separated the clinical groups from each other and from the controls. In addition, CVD severities, as classified into five clinical groups, were partially separable by linear discriminant analysis. Conclusions: Dysregulation of the plasma lipidome is characteristic of chronic inflammatory diseases. Lipid profiling accurately identifies the diseases and in the case of CVD also identifies sub-classes. Dysregulated lipids are partially but not fully counterbalanced by statin treatment. Clinical Trial Registration Details: This study was registered with the Clinical Trials number NCT04786431 Funding Information: This work was supported by PTDC/MED-PAT/29395/2017 financially supported by Fundacao paraKS is CEO and shareholder of of Lipotype GmbH. CL and MG are KS is CEO and shareholder of of Lipotype GmbH. CL and MG are employees of Lipotype GmbH. All other authors declare that they do not have any competing interestsemployees of Lipotype GmbH. All other authors declare that they do not have any competing interests424 a Ciencia e a Tecnologia (FCT), through national funds and co-funded by FEDER under the PT2020 Partnership. ND was a holder of PhD fellowship from the FCT (Ref. N°:SFRH/BD/51877/2012), attributed 10 by Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC). LA was a holder of a FCT PhD fellowship (PD/BD/114254/2016), attributed by the ProRegem Doctoral Programme in 2016. Declaration of Interests: KS is CEO and shareholder of of Lipotype GmbH. CL and MG are employees of Lipotype GmbH. All other authors declare that they do not have any competing interests. Ethics Approval Statement: The entire process was approved by the Ethical Review Board of the Faculty of Medicine of the New University of Lisbon and the Ethics Committee for Health of the Centro Hospitalar de Lisboa Ocidental, that includes the Hospital Santa Cruz, the Hospital Egas Moniz and Hospital Sao Francisco Xavier, and the Ethics Committee for Health of the Hospital Fernando Fonseca. All experiments were performed in accordance with the guidelines and regulations including, the Universal Declaration on Bioethics and Human Rights of UNESCO, 2005; The Charter of Fundamental rights of the EU, 2012; Ethical principles for medical research involving human subjects - Declaration of Helsinki, 2013; EU Regulation 2016/679 and Good Clinical Practice guidelines (Directive 2001/20/EC) and EU Clinical Trials Directive (2005/28/EC). Moreover, they complied with national legislations for the scientific use of human biological samples (Law No 12/2005 and No 131/2014).

© 2021 Taylor & Francis Group, LLC, This study aims to investigate if education (as a cognitive reserve proxy) modifies the profile of cognitive performance. We hypothesize that participants with higher education can remain functional (due to a better executive performance), despite a more severe memory impairment, compared with lower education individuals. One hundred and sixty-six mild cognitive impairment (MCI) individuals with at least one comprehensive neuropsychological evaluation were included in a retrospective, cross-sectional study and divided into two groups (Low Education-LE [1-4 years] and Medium-to-High Education-MHE [> 4 years]). A total of 22 neuropsychological measures were analyzed. Age-adjusted results were subject to simple regression analyses to determine the variance explained by education. Average scores and proportions of low performances were subject to group comparison. The results showed similar cognitive decline patterns between individuals with LE and MHE, with no significant difference in each cognitive domain. However, MHE revealed a steeper decline in certain cognitive domains, such as sustained attention and episodic memory, compared with the LE. Moreover, MHE showed a trend to higher proportion of tests affected when compared to LE. These suggest that individuals with higher education may remain in a MCI stage despite a more widespread cognitive impairment, reflecting a higher cognitive reserve.

Cross-sectional studies suggest a correlation between alterations in dream content reports and executive dysfunction tests in Parkinson's disease (PD), but this has not been assessed in longitudinal studies. Our objective was to assess the predictive value of dream content for progression of cognitive dysfunction in PD. We prospectively addressed all consecutive, non-demented patients with PD attending an outpatient clinic during a 1-year period. Dream reports were collected at baseline by means of a dream diary and analysed according to the Hall and Van de Castle system. Patients were assessed at baseline for rapid eye movement sleep behaviour disorder, motor stage, mood disorder and psychosis. The Montreal Cognitive Assessment (MoCA) was applied at baseline and 4 years later. Linear regression analysis was used to the test the relation between each dream index (predictors), demographic and other motor and non-motor variables (covariates), and change in MoCA scores (dependent variable). In all, 58 patients were assessed at both time points and 23 reported at least one dream (range 1-27, total 148). Aggression, physical activities, and negatively toned content predominated in dream reports. The MoCA scores decreased significantly from baseline to follow-up. In the multivariate model, negative emotion index was the strongest predictor of cognitive decline. We found a significant positive association between negative emotions in dreams at baseline and subsequent reduction in MoCA scores. These findings suggest that some dream content in patients with PD could be considered a predictor of cognitive decline, independent of other factors known to influence either dream content or cognitive deterioration.

Objective To assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients. Methods PD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores. Results We included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase. Conclusions The present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.

Our objectives were to assess the prevalence of REM sleep behaviour disorder in patients with Essential Tremor, using video-polysomnography and to compare REM sleep behaviour disorder features in essential tremor with those of patients with alpha-synucleinopathies. Forty-nine patients with essential tremor were screened with the REM Sleep Behaviour Disorder Screening Questionnaire. Patients scoring positive and those with spontaneous complaints of REM sleep behaviour disorder (n = 6) underwent video-polysomnography. The clinical features of essential tremor were compared between patients with and without REM sleep behaviour disorder. Video-polysomnography data were compared between patients who had essential tremor and Parkinson's disease with REM sleep behaviour disorder and those with idiopathic REM sleep behaviour disorder. Fourteen patients (23.5%) screened positive for REM sleep behaviour disorder, confirmed by video-polysomnography in five (11.6%). All patients with essential tremor and REM sleep behaviour disorder had rest tremor, compared with 13 (34.2%) in the group with essential tremor but without REM sleep behaviour disorder (p = .009). In video-polysomnography, patients with essential tremor and REM sleep behaviour disorder were similar to patients with Parkinson's disease with REM sleep behaviour disorder and presented worse sleep dysfunction and lower severity of REM sleep behaviour disorder compared to those with idiopathic REM sleep behaviour disorder. We found a high prevalence of REM sleep behaviour disorder in patients with essential tremor, associated with a predominance of rest tremor. Polysomnography data from patients with essential tremor and REM sleep behaviour disorder were similar to those in patients with Parkinson's disease. This suggests a relation between this subgroup of patients with essential tremor and the alpha-synucleinopathies.

Doubts persist regarding the influence of Parkinson's disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr-HY), incapacity (Schwab and England-S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale-NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index-CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS-mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

We thank the nursing staff at the Hospital Santa Cruz, in particular Edite Tomas Mateus and Manuel Belo Costa for their enthusiastic involvement in this project and help in blood collection. This work was supported by iNOVA4Health - UID/Multi/04462/2013, a program financially supported by FCT (Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education) through national funds and co-funded by FEDER under the PT2020 Partnership, and Programas de Atividades Conjuntas (PAC) (Ref. No 03/SAICT/2015). ND is a holder of PhD fellowship from the FCT (Ref. No: SFRH/BD/51877/2012). Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS, n = 74), or an ischemic stroke (IS, n = 21), or who suffer from stable angina pectoris (SAP, n = 78), and an age-matched control cohort (n = 52), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ratios of concentrations of CE to free cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort, indicating a deficient conversion of Chol to CE in the blood plasma in the CVD subjects. A non-equilibrium reaction quotient, Q′, describing the global homeostasis of cholesterol as manifested in the blood plasma was shown to have a value in the CVD cohorts (Q′ACS = 0.217 ± 0.084; Q′IS = 0.201 ± 0.084; Q′SAP = 0.220 ± 0.071) that was about one third less than in the control cohort (Q′Control = 0.320 ± 0.095, p < 1 × 10−4), suggesting its potential use as a rapid predictive/diagnostic measure of CVD-related irregularities in cholesterol homeostasis. publishersversion published

Background School students are an attractive target for stroke education due to the potential impact on stroke prevention and recognition. Additionally, these students can drive behavioral changes in their families. Aim To evaluate the impact of stroke education on school students, in terms of students’ and parents’ acquired stroke knowledge. Methods A structured questionnaire on knowledge of stroke was filled out by eighth-grade students and one of their parents in seven public schools. In four of these schools, students attended a stroke lecture; educational flyers and magnetic posters were distributed and parent education was encouraged. Students and parents of the other three schools were included in a control group. Students and parents, of both intervention and control groups, were resubmitted to the initial structured questionnaire within one week of the stroke lecture and three months later. Results We included 764 students and 344 parents, 383 (50.1%) and 210 (61.0%) in the intervention group. Correct test scores for students before, within one week, and three months after the intervention were 54.49% versus 55.03% (p = 0.418), 98.69% versus 60.89% (p Conclusions School-based interventions may improve stroke knowledge in middle school students and their parents.

Background and objective In acute stroke patients' treatment, time is of utmost importance. Significant efforts must be made to reduce door-to-needle time (DNT), taking into account its effect on treatment efficacy and patients' prognosis. The objective of this study is to assess the effect of implementing a countdown timer in the acute stroke emergency room, on door-to-computed tomography time (DCTT) and DNT. Methods Implementation of protocol that postulates the activation of a countdown timer every time an acute stroke patient is admitted. DCTT and DNT in patients submitted to thrombolysis were compared before and after the implementation of the chronometer. Multivariate analysis of DNT and DCTT was conducted adjusted to age, sex, National Institutes of Health Stroke Scale at admission, time from stroke onset to admission, and anterior circulation. Results Of the 76 patients treated with thrombolysis in 2015 in our hospital, 71 had stroke code activation by the emergency medical services or at hospital admission. Protocol was initiated on July 1, with 41 patients (58%) included in the second semester. The Stroke Chronometer implementation resulted in a reduction of the mean DCTT from 27.1 to 18.4 minutes ( P = .004; 95% CI 2.56-12.45) and of the mean DNT from 52.7 to 39.2 minutes ( P = .016; 95% CI 2.49-23.18), respectively, first and second semesters. Conclusion The Stroke Chronometer strategy has revealed to be an effective method to reduce DCTT and DNT.

A 45-year-old man presented with rapid progressive cognitive decline and behavioral symptoms. Neurologic examination revealed global cognitive impairment and episodic, nonrhythmic, brief contractions of the left orofacial muscles (video at [Neurology.org][1]). Serologic tests for syphilis were positive without HIV coinfection. CSF analysis revealed cell count 15/μL (mononuclear), hyperproteinorrachia (100 mg/dL), normal glycorrachia, intrathecal immunoglobulin G synthesis (index-3.09), oligoclonal bands (type 2), and venereal disease research laboratory titer of 1/4. MRI revealed bilateral nonspecific white matter changes. Although rare and seldom documented, this dyskinesia, coined candy sign, is considered pathognomonic of neurosyphilis.1 Improvement with penicillin was observed, but response to treatment seems to be variable.2 [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000003544