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Physician burnout has a negative impact on both physicians and patients. Limited information is available on professional burnout of neurologists. The aim of this study was to assess the presence of burnout among neurologists caring for patients with cognitive disorders and to identify associated factors. An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists involved in the care of patients with cognitive disorders answered a survey composed of demographic characteristics, professional background, clinical practice setting, and behavioral factors. Burnout was assessed using a single-item measure from the Physician Work Life Study. A multivariate logistic regression analysis was conducted to determine the association between neurologists' characteristics and burnout. A total of 188 neurologists answered the survey. The mean age (standard deviation-SD) was 40.6 (11.3) years and 52.7% were male. The majority of participants were general neurologists (60.6%) who attending a median of 20 patients with cognitive disorders (interquartile range 10.0-30.0) weekly. Thirty-nine participants (20.7%) reported burnout. Participants with burnout had greater experiences of regret associated with past clinical decisions than their counterparts (mean Regret Intensity Scale scores of 2.3 and 1.9, respectively; p = 0.003). Burnout was associated with non-academic practice (OR = 3.02 [95% CI 1.18, 7.73], p = 0.021) and care-related regret (OR = 2.53 [95% CI 1.13, 5.64], p = 0.023) in the multivariate analysis after adjustment for confounders. Professional burnout was a common phenomenon among neurologists managing cognitive disorders. Identifying physician burnout and its associated factors may be critical for implementing preventive intervention strategies.

Huntington’s disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex ® , a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex ® and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor ( p  = 0.286), cognitive ( p  = 0.824), behavioral ( p  = 1.0) and functional ( p  = 0.581) scores were detected during treatment with Sativex ® as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex ® is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations. Clincaltrals.gov identifier: NCT01502046

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. Methods An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Summary of opinion Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer’s disease (AD), including those with MCI due to AD (prodromal AD). Conclusion Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a multimodal management approach including lifestyle risk factor modification and consideration of the multinutrient Souvenaid.

Background There are few updated studies on the prevalence and management of Alzheimer’s disease (AD), which could be underdiagnosed or undertreated. The COVID-19 pandemic may have worsened the deficiencies in the diagnosis and treatment of these patients. Electronic medical records (EMR) offer an opportunity to assess the impact and management of medical processes and contingencies in the population. Objective To estimate AD prevalence in Spain over a 6-year period, based on treated patients, according to usual clinical practice. Additionally, to describe the management of AD-treated patients and the evolution of that treatment during the 2020 COVID-19 pandemic. Methods Retrospective study using the Spanish IQVIA EMR database. Patients treated with donepezil, galantamine, rivastigmine, and/or memantine were included in the study. Annual AD prevalence (2015–2020) was estimated and extrapolated to the national population level. Most frequent treatments and involved specialties were described. To assess the effect of COVID-19, the incidence of new AD cases in 2020 was calculated and compared with newly diagnosed cases in 2019. Results Crude AD prevalence (2015–2020) was estimated at 760.5 per 100,000 inhabitants, and age-standardized prevalence (2020) was 664.6 (male 595.7, female 711.0). Monotherapy was the most frequent way to treat AD (86.2%), in comparison with dual therapy (13.8%); rivastigmine was the most prescribed treatment (37.3%), followed by memantine (36.4%) and donepezil (33.0%). Rivastigmine was also the most utilized medication in newly treated patients (46.7%), followed by donepezil (29.8%), although donepezil persistence was longer (22.5 vs. 20.6 months). Overall, donepezil 10 mg, rivastigmine 9.5 mg, and memantine 20 mg were the most prescribed presentations. The incidence rate of AD decreased from 148.1/100,000 (95% confidence interval [CI] 147.0–149.2) in 2019 to 118.4/100,000 (95% CI 117.5–119.4) in 2020. Conclusions The obtained prevalence of AD-treated patients was consistent with previous face-to-face studies. In contrast with previous studies, rivastigmine, rather than donepezil, was the most frequent treatment. A decrease in the incidence of AD-treated patients was observed during 2020 in comparison with 2019, presumably due to the significant impact of the COVID-19 pandemic on both diagnosis and treatment. EMR databases emerge as valuable tools to monitor in real time the incidence and management of medical conditions in the population, as well as to assess the health impact of global contingencies and interventions.

Background The APOE ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and is associated with increased risk of amyloid-related imaging abnormalities (ARIA) during anti-amyloid therapy. Accurate identification of ε4 carriers, particularly APOE ε4/ε4 individuals, is clinically relevant. This study outlines the development and validation of e4Quant, a novel turbidimetric assay for quantifying plasma ApoE4 as a non-genetic alternative to APOE genotyping. Methods The e4Quant test utilizes a proprietary particle-enhanced immunoturbidimetry method, employing an isoform-specific anti-ApoE4 antibody on standard chemistry analyzers. Plasma samples from 160 individuals of known APOE genotype (35 APOE ε4/ε4 homozygotes, 115 APOE ε4 heterozygotes, and 10 APOE ε4 non-carriers) were analyzed for ApoE4 and total ApoE levels. The test’s discriminatory performance was assessed by ROC analysis and two-threshold classification algorithms. Results ApoE4 levels ascertained by the e4Quant test exhibited clear genotype-dependent stratification. ROC analysis indicated 100% sensitivity and specificity in distinguishing APOE ε4 carriers from non-carriers, and 88.6% sensitivity and 90.4% specificity for discriminating homozygous from heterozygous carriers. Normalizing ApoE4 to total ApoE improved classification (sensitivity 94.3%, specificity 93.9%). A combined ratio-plus-concentration approach further enhanced discrimination (sensitivity 91.4%, specificity 100%). Three ε4 homozygous samples with low ApoE4/total ApoE ratios were misclassified. Discussion The e4Quant assay offers a rapid, cost-effective, and highly accurate biochemical alternative to APOE genotyping, suitable for clinical and research settings, particularly in assessing AD risk and optimizing anti-amyloid therapeutic strategies. One subgroup of APOE ε4/ε4 subjects had unexpectedly low ApoE4 levels, raising questions about potential biological heterogeneity and its impact on Alzheimer’s disease biology. Conclusion The e4Quant assay is a novel alternative for genotyping to determine APOE ε4 carrier status, while also providing quantitative measurements of ApoE4 levels. Its high diagnostic accuracy, ease of use in standard clinical laboratories, and potential utility for personalized medicine in AD treatment highlight its translational value. Further studies are warranted to investigate the clinical significance of APOE ε4 expression variability and its impact on disease progression and treatment response.

Widespread access to emerging information and communication technologies (ICT) allows its use for screening of diseases in the general population. At the initiative of the Spanish Confederation of Associations of Families of People with Alzheimer's disease and other dementias (CEAFA), a website (http://www.problemasmemoria.com) has been created that provides information about Alzheimer’s disease and include questionnaires to be completed by family or friends concerned about memory problems of a relative. A cross-sectional, randomized, multicenter study was performed to evaluate feasibility, validity, and user satisfaction with an electronic method of completion versus the current method of paper-based questionnaires for clinically dementia screening completed by the informants: the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and the Alzheimer’s disease-8 screening test (AD8). A total of 111 pairs were recruited by seven memory clinics. Informants completed IQCODE and AD8 questionnaires both in their paper and electronic versions. The correlation between paper and electronic versions was significantly positive for IQCODE (r= 0.98; p< 0.001) and AD8 (r= 0.96; p< 0.001). The execution time did not differ significantly, and participants considered their use equally easy. This study shows that an electronic version of the IQCODE and AD8 questionnaires are suitable for its on-line use via internet and achieve the same results as the traditional paper versions.

Raising knowledge about Alzheimer's disease (AD) may help in identifying the disorder, seeking earlier appropriate healthcare, and decreasing its stigma. The aim of this study was to determine the knowledge and perceptions towards people with AD among employees of a pharmaceutical company in Spain. A non-interventional, cross-sectional study was conducted among 447 employees. Participants answered demographic questions and completed the Alzheimer's Disease Knowledge Scale (ADKS). Caregivers also answered questions related to their personal experience with patients with AD and completed the Satisfaction with Life Scale (SWLS), the Revised Memory and Behavior Problems Checklist (RMBPC), and the Beck Depression Inventory-Fast Screen (BDI-FS). Participants were mostly between 30 and 50 years old (63%), female (65.3%), and had bachelor or master degrees (82.7%). Forty-two (9.4%) of participants were caregivers, mainly of moderate to severe dementia subjects. Overall knowledge about AD was moderate (mean ADKS score = 21.2 ± 2.8 [70.6% of correct answers]). Risk factors and caregiving were the domains with lowest scores (correct answers: 58.58% and 63%, respectively). Mean total ADKS score was significantly higher in participants caring for people with AD compared with non-caregivers (22.1 ± 2.9 and 21.0 ± 2.8; p=0.02, respectively). There was no statistically significant association between total ADKS score and age, sex, educational level, or relative's AD severity. Most caregivers were satisfied with life (mean SWLS score = 26.8 ± 5.6) showing a low impact from behavioral problems (mean RMBPC reaction score = 26.81 ± 20.2). Six of them (14.3%) were scored as depressed. There is a continuing need to improve understanding of AD to fill the gaps in knowledge of the disease, even in a population working in healthcare sector with a high educational level.

The allele ε4 of the apolipoprotein E gene ( APOE ε4) is the major genetic risk factor for non-dominantly inherited Alzheimer’s Disease (AD). Current techniques for APOE ε4 carriers identification show good accuracy but have several disadvantages that limit its implementation in a clinical laboratory. These include the need for sample preprocessing, poor automation, low throughput, requirement of additional equipment, and high cost. We followed ISO 13485 guidelines to validate the e 4 Risk test , a new latex-enhanced immunoturbidimetric blood assay for apolipoprotein E4 (ApoE4) determination in human plasma samples. The test showed high performance in terms of lot to lot variability, precision, interferences, reagents stability, prozone, and detectability. Furthermore, diagnostic accuracy is almost equal (99%) to the gold standard, APOE ε4 genotyping by polymerase chain reaction (PCR). Furthermore, we demonstrated that the e 4 Risk test can be adapted to any clinical chemistry analyzer, including the high throughput analyzers present in most hospitals and clinical laboratories. The e4Risk test versatility, low cost, and easiness provides an excellent solution for APOE ε4 carriers identification using the same blood sample drawn for biochemical diagnostic work-up of AD patients, which can have important advantages for patient stratification in clinical trials, preventative strategies for AD, and clinical assessment of risk for brain amyloidosis.

BackgroundPhysician burnout has a negative impact on both physicians and patients. Limited information is available on professional burnout of neurologists. The aim of this study was to assess the presence of burnout among neurologists caring for patients with cognitive disorders and to identify associated factors.MethodsAn online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists involved in the care of patients with cognitive disorders answered a survey composed of demographic characteristics, professional background, clinical practice setting, and behavioral factors. Burnout was assessed using a single-item measure from the Physician Work Life Study. A multivariate logistic regression analysis was conducted to determine the association between neurologists' characteristics and burnout.ResultsA total of 188 neurologists answered the survey. The mean age (standard deviation-SD) was 40.6 (11.3) years and 52.7% were male. The majority of participants were general neurologists (60.6%) who attending a median of 20 patients with cognitive disorders (interquartile range 10.0-30.0) weekly. Thirty-nine participants (20.7%) reported burnout. Participants with burnout had greater experiences of regret associated with past clinical decisions than their counterparts (mean Regret Intensity Scale scores of 2.3 and 1.9, respectively; p = 0.003). Burnout was associated with non-academic practice (OR = 3.02 [95% CI 1.18, 7.73], p = 0.021) and care-related regret (OR = 2.53 [95% CI 1.13, 5.64], p = 0.023) in the multivariate analysis after adjustment for confounders.ConclusionsProfessional burnout was a common phenomenon among neurologists managing cognitive disorders. Identifying physician burnout and its associated factors may be critical for implementing preventive intervention strategies.

ObjectivesSubstantia nigra hyperechogenicity (SN+) detected by transcranial ultrasound (TUS) is useful for Parkinson’s disease (PD) diagnosis. Approximately 15% false negative results of unknown significance are reported. However, most TUS studies are transversal, and diagnosis of PD may change during follow-up.MethodsAnalysis of our prospective registry of TUS in clinical practice, selecting patients with sufficient bone window, to whom TUS was performed because of suspected PD, and a minimum of 3-year follow-up. Subjects were classified regarding SN echogenicity (SN+/SN−).Results172 patients (122 SN+, 50 SN−), mean age 71 years (25–90), were included. At the end of follow-up, PD diagnosis was retained by 91% SN+ vs. 54% SN− subjects (p < 0.0001), while final diagnosis of atypical parkinsonism (3%SN+ vs. 16%SN−, p:0.0059) was more frequent in SN−. Dopaminergic therapy response was associated with SN+ (88% SN+ vs. 50% SN−, p < 0.0001), as were abnormal DaTSCANs (90%SN+ vs. 56%SN−, p 0.0027). SN echogenicity had 80% sensitivity and 68% specificity for PD diagnosis, while SPECT had 91% and 73%, respectively. SN+ was the only baseline predictor of keeping PD diagnosis at the end of follow-up, with an odds ratio of 12 (95% CI 3–42) (p < 0.001).ConclusionsIn our sample of patients with suspected PD, SN hyperechogenicity predicted PD diagnosis in the long term with a high odds ratio. Conversely, a baseline normal SN echogenicity was associated with a poorer response to PD therapy and change to a different diagnosis from PD. Normal SN appears to be a caveat for clinicians to check for atypical parkinsonism features during follow-up.