Unveiling the role of subjective cognitive complaints in predicting cognitive impairment in Parkinson´s Disease- A longitudinal study with 4 year of follow up.

BACKGROUND: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). OBJECTIVE: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. METHODS: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. RESULTS: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. CONCLUSION: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints.

REM sleep behaviour disorder in essential tremor: A polysomnographic study.

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.

Do dreams tell the future? Dream content as a predictor of cognitive deterioration in Parkinson's disease.

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.

Motor and non-motor function predictors of mortality in Parkinson's disease.

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.

Bismuth encephalopathy- a rare complication of long-standing use of bismuth subsalicylate.

BACKGROUND: Drugs containing bismuth, although usually safe, may rarely cause neurotoxicity. CASE PRESENTATION: We describe the case of a 44-year-old woman treated with bismuth subsalicylate for about 20 years, who developed abnormal behaviour and postural instability in two weeks. On examination, she had greyish discoloration of teeth, was confused and presented generalized myoclonic jerks. In the next days, her clinical condition deteriorated, with a reduction in alertness and more exuberant myoclonus. Brain MRI was unremarkable. CSF revealed mild elevation of protein content (47 mg/dL; reference range: 15-45 mg/dL) and elevation of white blood cell count (10/µL). Bismuth levels in urine (375 µg/L), serum (260 µg/L) and CSF (21.4 µg/L) samples were highly above the threshold for toxicity. Following supportive treatment and bismuth discontinuation, she made a full recovery within weeks. CONCLUSIONS: Although rare, bismuth encephalopathy should be considered in patients presenting with subacute encephalopathy and myoclonus. This encephalopathy can be subacute even after a chronic exposure. Cessation of bismuth can lead to a complete resolution in weeks.

The Stroke Chronometer-A New Strategy to Reduce Door-to-Needle Time.

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.

Effect of education on cognitive performance in patients with mild cognitive impairment.

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.

Obstructive Sleep Apnea and Other Vascular Risk factors' Impact on Non-Motor Symptoms in Parkinson's Disease.

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.

Objective sleep data as predictors of cognitive decline in dementia with Lewy Bodies and Parkinson's disease.

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.

Progression in Parkinson's Disease: Variation in Motor and Non-motor Symptoms Severity and Predictors of Decline in Cognition, Motor Function, Disability, and Health-Related Quality of Life as Assessed by Two Different Methods.

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.

Polysomnographic predictors of sleep, motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study.

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.

Shotgun mass spectrometry-based lipid profiling identifies and distinguishes between chronic inflammatory diseases.

BACKGROUND: Localized stress and cell death in chronic inflammatory diseases may release tissue-specific lipids into the circulation causing the blood plasma lipidome to reflect the type of inflammation. However, deep lipid profiles of major chronic inflammatory diseases have not been compared. METHODS: Plasma lipidomes of patients suffering from two etiologically distinct chronic inflammatory diseases, atherosclerosis-related vascular disease, including cardiovascular (CVD) and ischemic stroke (IS), and systemic lupus erythematosus (SLE), were screened by a top-down shotgun mass spectrometry-based analysis without liquid chromatographic separation and compared to each other and to age-matched controls. Lipid profiling of 596 lipids was performed on a cohort of 427 individuals. Machine learning classifiers based on the plasma lipidomes were used to distinguish the two chronic inflammatory diseases from each other and from the controls. FINDINGS: Analysis of the lipidomes enabled separation of the studied chronic inflammatory diseases from controls based on independent validation test set classification performance (CVD vs control - Sensitivity: 0.94, Specificity: 0.88; IS vs control - Sensitivity: 1.0, Specificity: 1.0; SLE vs control - Sensitivity: 1, Specificity: 0.93) and from each other (SLE vs CVD ‒ Sensitivity: 0.91, Specificity: 1; IS vs SLE - Sensitivity: 1, Specificity: 0.82). Preliminary linear discriminant analysis plots using all data clearly separated the clinical groups from each other and from the controls, and partially separated CVD severities, as classified into five clinical groups. Dysregulated lipids are partially but not fully counterbalanced by statin treatment. INTERPRETATION: 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. FUNDING: Full list of funding sources at the end of the manuscript.

Polysomnographic data in Dementia with Lewy Bodies: correlation with clinical symptoms and comparison with other α-synucleinopathies.

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.

Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients.

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.

Impact of stroke education on middle school students and their parents: A cluster randomized trial.

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 < 0.001), and 95.58% versus 75.7% (p < 0.001) in the intervention and control groups, respectively. Correct test scores for parents at the same time points were 68.78% versus 64.47% (p = 0.107), 96.89% versus 71.42% (p < 0.001), and 94.58% versus 76.54% (p < 0.001) in the intervention and control groups, respectively. Conclusions School-based interventions may improve stroke knowledge in middle school students and their parents.

A Young Woman with Ischemic Stroke: Should We Pay More Attention to Varicella Zoster Infection?

Ischemic and hemorrhagic stroke are recognized complications of Varicella zoster virus (VZV) infections, although uncommon and poorly documented. The authors report the case of a 31-year-old woman admitted with acute ischemic stroke of the right posterior cerebral artery and a history of a thoracic rash 1 month before. Aspirin and simvastatin were prescribed, but the patient suffered a stepwise deterioration the following days, with new areas of infarction on brain imaging. Despite no evidence of cardiac or large vessel embolic sources, anticoagulation was started empirically 6 days after stroke onset. One week later, symptomatic hemorrhagic transformation occurred. The diagnosis of VZV vasculopathy was then considered, and treatment with acyclovir and prednisolone was started with no further vascular events. Cerebrospinal fluid analysis and digital subtraction angiography findings corroborated the diagnosis. The patient was discharged to the rehabilitation center with a modified Rankin scale (mRS) score of 4. On the 6-month follow-up, she presented only a slight disability (mRS score 2). In conclusion, VZV vasculopathy needs to be considered in young adults with stroke. A high index of suspicion and early treatment seem to be important to minimize morbidity and mortality. Anticoagulation should probably be avoided in stroke associated with VZV vasculopathy.