Design of a Non-Interventional Study to Assess Neurologists' Perspectives and Pharmacological Treatment Decisions in Early Alzheimer's Disease.

INTRODUCTION: The current therapeutic landscape of Alzheimer's disease (AD) is evolving rapidly. Our treatment options include new anti-amyloid-ß protein disease-modifying therapies (DMTs) that decrease cognitive decline in patients with early AD (prodromal and mild AD dementia). Despite these advances, we have limited information on how neurologists would apply the results of recent DMT trials to make treatment decisions. Our goal is to identify factors associated with the use of new AD DMTs among neurologists applying concepts from behavioral economics. METHODS: This non-interventional, cross-sectional, web-based study will assess 400 neurologists with expertise in AD from across Spain. Participants will start by completing demographic information, practice settings, and a behavioral battery to address their tolerance to uncertainty and risk preferences. Participants will then be presented with 10 simulated case scenarios or vignettes of common encounters in patients with early AD to evaluate treatment initiation with anti-amyloid-ß DMTs (e.g., aducanumab, lecanemab, etc.). The primary outcomes will be therapeutic inertia and suboptimal decisions. Discrete choice experiments will be used to determine the weight of factors influencing treatment choices. RESULTS: The results of this study will provide new insights into a better understanding of the most relevant factors associated with therapeutic decisions on the use of DMTs, assessing how neurologists handle uncertainty when making treatment choices, and identifying the prevalence of therapeutic inertia in the management of early AD.

Comparison of the Results of a Parkinson's Holter Monitor With Patient Diaries, in Real Conditions of Use: A Sub-analysis of the MoMoPa-EC Clinical Trial.

Background: For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools-Sense4Care's STAT-ON-can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed. Methods: Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data. Results: The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.73) for the OFF time (%), 0.48 (95% CI: 0.17-0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44-0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was -0.63 (p < 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS. Conclusion: This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary. Trial Registration: https://clinicaltrials.gov/show/NCT04176302 (NCT04176302).

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol.

INTRODUCTION: In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. METHODS AND ANALYSIS: This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson's Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months.The primary outcome is the efficiency of the Parkinson's Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor-patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective.Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022. TRIAL REGISTRATION: NCT04176302; https://clinicaltrials.gov/show/NCT04176302.

Cognitive Impairment Is a Common Comorbidity in Deceased COVID-19 Patients: A Hospital-Based Retrospective Cohort Study.

We analyzed the frequency of cognitive impairment (CI) in deceased COVID-19 patients at a tertiary hospital in Spain. Among the 477 adult cases who died after admission from March 1 to March 31, 2020, 281 had confirmed COVID-19. CI (21.1% dementia and 8.9% mild cognitive impairment) was a common comorbidity. Subjects with CI were older, tended to live in nursing homes, had shorter time from symptom onset to death, and were rarely admitted to the ICU, receiving palliative care more often. CI is a frequent comorbidity in deceased COVID-19 subjects and is associated with differences in care.

Principales complicaciones neurológicas de los cánceres nefrourológicos / Major neurological complications of genitourinary cancers

Introducción. Los cánceres nefrourológicos constituyen un conjunto heterogéneo y cada vez más frecuente de tumores malignos que poseen el potencial de derivar directamente, e indirectamente por el tratamiento aplicado, en una serie de complicaciones neurológicas que impactan negativamente sobre la calidad de vida de los pacientes. Objetivo. Exponer los datos más relevantes sobre las principales complicaciones neurológicas de los cánceres nefrourológicos. Desarrollo. Búsqueda de artículos en PubMed, últimos libros y principales guías de práctica clínica y sociedades científicas publicados referentes al diagnóstico y tratamiento de dichas complicaciones. Conclusiones. Las complicaciones neurológicas de los cánceres nefrourológicos generan una carga importante de morbimortalidad en los pacientes oncológicos. Paradójicamente, gracias al aumento de su supervivencia, también se incrementa la probabilidad de producirse metástasis en el sistema nervioso o efectos adversos por el tratamiento, en especial la quimioterapia. Actualmente, el diagnóstico y el tratamiento de las complicaciones neurológicas asociadas a los cánceres nefrourológicos suponen un área muy importante de interés creciente para el desarrollo de trabajos de investigación que permitan mejorar el pronóstico y la calidad de vida de estos pacientes y de sus familiares o cuidadores. Para ello, es preciso conocer mejor la etiopatogenia y la fisiopatología que llevan a la aparición de este tipo de complicaciones, particularmente los síndromes paraneoplásicos, y, por otro lado, la realización de ensayos clínicos controlados, aleatorizados, bien diseñados, que amplíen el arsenal terapéutico con nuevos fármacos quimioterápicos con mayor efectividad antineoplásica y mejor seguridad relativa a los efectos secundarios neurotóxicos

Introduction. Genitourinary cancers constitute a heterogeneous and increasingly frequent group of malignant tumors that have the potential to derive directly, or indirectly from the treatment applied, in a series of neurological complications that negatively impact on the quality of life of the patients who suff er them. Aims. To report the most relevant data on the main neurological complications of genitourinary cancers. Development. We conducted a PubMed search for articles, latest books, leading clinical practice guidelines, and scientific societies, regarding the appearance of such complications. Conclusions. Neurological complications of genitourinary cancers generate a signifi cant burden of morbidity and ortality in cancer patients. In a paradoxical manner, owing to the raised survival of these patients, the likelihood of metastatization at the nervous system level and/or adverse eff ects related to the treatment received, especially due to chemotherapy, is also increased. Currently, diagnosis and management of neurological complications associated with genitourinary cancers represent a very important area of growing interest for the development of research projects that allow to improve the prognosis and quality of life genitourinary cancers subjects and their relatives and/or caregivers. For this purpose, it is necessary to know more about the etiopathogenesis and pathophysiology that lead to the occurrence of these type of complications in genitourinary cancers individuals, in particular paraneoplastic syndromes. Moreover, on the other hand, to carry out further well-designed randomized controlled clinical trials that expand the therapeutic arsenal with new chemotherapeutic drugs that possess a better antineoplastic eff ectiveness and improve the safety related to the neurotoxic side effects

A Kinematic Sensor and Algorithm to Detect Motor Fluctuations in Parkinson Disease: Validation Study Under Real Conditions of Use.

BACKGROUND: A new algorithm has been developed, which combines information on gait bradykinesia and dyskinesia provided by a single kinematic sensor located on the waist of Parkinson disease (PD) patients to detect motor fluctuations (On- and Off-periods). OBJECTIVE: The goal of this study was to analyze the accuracy of this algorithm under real conditions of use. METHODS: This validation study of a motor-fluctuation detection algorithm was conducted on a sample of 23 patients with advanced PD. Patients were asked to wear the kinematic sensor for 1 to 3 days at home, while simultaneously keeping a diary of their On- and Off-periods. During this testing, researchers were not present, and patients continued to carry on their usual daily activities in their natural environment. The algorithm's outputs were compared with the patients' records, which were used as the gold standard. RESULTS: The algorithm produced 37% more results than the patients' records (671 vs 489). The positive predictive value of the algorithm to detect Off-periods, as compared with the patients' records, was 92% (95% CI 87.33%-97.3%) and the negative predictive value was 94% (95% CI 90.71%-97.1%); the overall classification accuracy was 92.20%. CONCLUSIONS: The kinematic sensor and the algorithm for detection of motor-fluctuations validated in this study are an accurate and useful tool for monitoring PD patients with difficult-to-control motor fluctuations in the outpatient setting.

Amyloid pet in primary progressive aphasia: case series and systematic review of the literature.

Primary progressive aphasia (PPA) is considered a heterogeneous syndrome, with different clinical subtypes and neuropathological causes. Novel PET biomarkers may help to predict the underlying neuropathology, but many aspects remain unclear. We studied the relationship between amyloid PET and PPA variant in a clinical series of PPA patients. A systematic review of the literature was performed. Patients with PPA were assessed over a 2-year period and classified based on language testing and the International Consensus Criteria as non-fluent/agrammatic (nfvPPA), semantic (svPPA), logopenic variant (lvPPA) or as unclassifiable (ucPPA). All patients underwent a Florbetapir (18-F) PET scan and images were analysed by two nuclear medicine physicians, using a previously validated reading method. Relevant studies published between January 2004 and January 2016 were identified by searching Medline and Web of Science databases. Twenty-four PPA patients were included (13 women, mean age 68.8, SD 8.3 years; range 54-83). Overall, 13/24 were amyloid positive: 0/2 (0%) nfvPPA, 0/4 (0%) svPPA, 10/14 (71.4%) lvPPA and 3/4 (75%) ucPPA (p = 0.028). The systematic review identified seven relevant studies, six including all PPA variants and one only lvPPA. Pooling all studies together, amyloid PET positivity was 122/224 (54.5%) for PPA, 14/52 (26.9%) for nfvPPA, 6/47 (12.8%) for svPPA, 101/119 for lvPPA (84.9%) and 12/22 (54.5%) for ucPPA. Amyloid PET may help to identify the underlying neuropathology in PPA. It could be especially useful in ucPPA, because in these cases it is more difficult to predict pathology. ucPPA is frequently associated with amyloid pathology.

Validation of a portable device for mapping motor and gait disturbances in Parkinson's disease.

BACKGROUND: Patients with severe idiopathic Parkinson's disease experience motor fluctuations, which are often difficult to control. Accurate mapping of such motor fluctuations could help improve patients' treatment. OBJECTIVE: The objective of the study was to focus on developing and validating an automatic detector of motor fluctuations. The device is small, wearable, and detects the motor phase while the patients walk in their daily activities. METHODS: Algorithms for detection of motor fluctuations were developed on the basis of experimental data from 20 patients who were asked to wear the detector while performing different daily life activities, both in controlled (laboratory) and noncontrolled environments. Patients with motor fluctuations completed the experimental protocol twice: (1) once in the ON, and (2) once in the OFF phase. The validity of the algorithms was tested on 15 different patients who were asked to wear the detector for several hours while performing daily activities in their habitual environments. In order to assess the validity of detector measurements, the results of the algorithms were compared with data collected by trained observers who were accompanying the patients all the time. RESULTS: The motor fluctuation detector showed a mean sensitivity of 0.96 (median 1; interquartile range, IQR, 0.93-1) and specificity of 0.94 (median 0.96; IQR, 0.90-1). CONCLUSIONS: ON/OFF motor fluctuations in Parkinson's patients can be detected with a single sensor, which can be worn in everyday life.

A blood-based, 7-metabolite signature for the early diagnosis of Alzheimer's disease.

Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of seven metabolites: three amino acids (glutamic acid, alanine, and aspartic acid), one non-esterified fatty acid (22:6n-3, DHA), one bile acid (deoxycholic acid), one phosphatidylethanolamine [PE(36:4)], and one sphingomyelin [SM(39:1)]. Detailed analysis ruled out the influence of potential confounding variables, including comorbidities and treatments, on each of the seven biomarkers. The final model accurately distinguished AD from NC patients (AUC, 0.918). Importantly, the model also distinguished aMCI from NC patients (AUC, 0.826), indicating its potential diagnostic utility in early disease stages. These findings describe a sensitive biomarker panel that may facilitate the specific detection of early-stage AD through the analysis of plasma samples.

Análisis de las derivaciones por trastorno cognitivo a consultas externas de neurología: investigando la probabilidad pretest de deterioro cognitivo y demencia / Analysis of referrals by cognitive disorder in outpatient neurology clinic: investigating pretest probability of cognitive impairment and dementia

La probabilidad de presentar un trastorno depende más de la exactitud con que se haya determinado la probabilidad pretest que de las características de las pruebas diagnósticas empleadas. Se analizó a todos los pacientes derivados a consultas externas de neurología por sospecha de trastorno cognitivo durante 3 años. Se registraron 519 primeras consultas derivadas para evaluación cognitiva (8,5 % del total). En el 41,4 % se diagnosticó algún trastorno cognitivo (15,4% DCL y 26,0 % demencia). La probabilidad pretest se relacionó con la edad, la presencia de depresión y de trastorno conductual. En el subgrupo de 18-50 años la probabilidad pretest para presentar deterioro cognitivo fue del 3,4 % comparada con un 73,8 % en el subgrupo de >80 años. La presencia de trastornos de conducta aumentó la probabilidad pretest en todos los grupos (globalmente, del 41,4 % al 81,0 %) y, en cambio, la depresión redujo la probabilidad pretest (globalmente, del 41,4 % al 26,0 %). La edad, la presencia (o ausencia) de depresión y la existencia de un trastorno conductual influyen significati vamente en la probabilidad pretest. Es fundamental conocer la probabilidad pretest a la hora de tomar una decisión sobre las pruebas diagnósticas en la neurología de la conducta(AU)

The probability of a disorder depends more on the accuracy of pretest probability than characteristics of the diagnostic tests employed. We analyzed all patients referred to neurology outpatients with suspected cognitive disorder for 3 years. There were 519 first consultations referred for cognitive assessment (8.5 % of total). In 41.4 % subjects were diagnosed with a cognitive disorder (15.4 % MCI and 26.0 % dementia). The pretest probability was associated with age, presence (or absence) of depression and presence of neuropsychiatric symptoms. In the subgroup of 18-50 years pretest probability to present cognitive impairment was 3.4 % compared with 73.8 % in the subgroup of >80 years. The presence of neuropsychiatric symptoms increased the pretest probability in all groups (overall 41.4 % to 81.0 %) and depression reduced the pretest probability (overall 41.4 % to 26.0 %). Age, the presence (or absence) of depression and the existence of neuropsychiatric symptoms influence significantly over pretest probability. Neurologist needs to know the pretest probability when they are making a clinical decision about diagnostic testing in behavioral neurology(AU)

Consenso para la elaboración del informe de alta hospitalaria en especialidades médicas / Consensus for hospital discharge reports in medical specialities

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Treatment of Parkinson's disease could be regulated by movement sensors: subcutaneous infusion of varying apomorphine doses according to the intensity of motor activity.

Most recent therapeutic solutions to treat Parkinson's disease seek continuous administration of dopaminergic agonists, as for example rigotine patches or apomorphine infusion pumps. Such drug-delivery devices are aimed at preventing fluctuations in drug plasma levels, which could cause certain symptoms such as wearing-off periods or dyskinesia. However, we postulate that drug plasma levels should not keep constant, but rather adjust to the varying intensity of the different user's activities. The rationale behind this is that the drug amount appropriate to treat a patient at rest is lower than that required to treat the same patient when engaged in physical activity. We propose dynamic real-time dose adjustment, so that the doses increase as the patient starts performing physical activity, thus preventing off periods such as "freeze" phenomenon, and the doses reduce during the resting periods, thus preventing adverse effects. Small portable movement sensors are currently available, which detect the amount and type of activity in a continuous way. Combining such technology with infusion pumps to produce modified pumps capable of adjusting the infusion rate to the user's activity, seems to be feasible in the short-term.

Magnetic resonance image-reversible findings in a patient with general paresis.

MATERIAL AND METHODS: We describe clinical, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) findings in a patient with general paresis. MRI demonstrated cortical-subcortical atrophy and broad-coalescent high-intensity T2 lesions in right frontotemporal lobes. RESULTS: After intravenous penicillin therapy, the size of these lesions diminished dramatically. That regression correlated with improvement in neuropsychologic test and CSF analysis. CONCLUSION: To our knowledge, this is the first case reported in the literature of MRI-reversible lesions in a patient with general paresis. We suggest that MRI is of prognostic value in patients with general paresis. Severe atrophy, especially in the temporal lobe, could be a marker of bad clinical outcome.