Publications by authors named "Raphael Wurm"

Purpose: A significant proportion of the population reports a positive family history of dementia, which correlates with higher disease risk. As therapeutic advances raise awareness of genetic factors, memory clinics need clear guidelines for identifying patients who would benefit from genetic testing. We aimed to assess the proportion of patients with positive family history in our cohort and a method to improve identification of high-risk genes.

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Background: Sacubitril/valsartan is a key therapy for heart failure with reduced ejection fraction (HFrEF). However, concerns remain regarding its potential impact on cognitive function, because neprilysin inhibition may influence amyloid-β (Aβ) metabolism. This study evaluates the effect of sacubitril/valsartan on plasma biomarkers of neurodegeneration.

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Importance: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, rapidly progressive and fatal neurodegenerative disease. Definite sCJD diagnosis can only be made post mortem, and little is known about the prodromal phase of the disease.

Objective: To compare drug prescription patterns before the clinical onset of sCJD between patients and matched controls for exploration of potential risk factors and to assess correlations between drug exposure and sCJD survival.

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Introduction: With the advent of disease-modifying therapies, accurate assessment of biomarkers indicating the presence of disease-associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography (Aβ PET) biomarkers in a real-world memory-clinic setting to develop an efficient algorithm for clinical use.

Methods: Patients were evaluated for AD-related Aβ pathology from two independent cohorts (Ludwig Maximilian University [LMU],  = 402, and Medical University of Vienna [MUV],  = 144).

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Background And Purpose: The European Academy of Neurology (EAN) has adhered to the global plan for reducing the burden of neurological disorders and promoting brain health launched by the World Health Organisation (WHO), the WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders. This study reports the results of an EAN survey among national neurological societies (NNSs) on their awareness of brain health policies.

Methods: The EAN survey on the current state of national brain health policies was conducted among the 47 presidents of the NNSs affiliated with the EAN, with the aim of developing the best strategy for close collaboration among stakeholders.

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Objective: In light of clinical trials and disease-modifying therapies, an early identification of patients at-risk of developing Alzheimer's disease (AD) is crucial. Blood-based biomarkers have shown promising results regarding the in vivo detection of the earliest neuropathological changes in AD. Herein, we investigated the ability of plasma p-tau181 to act as a prescreening marker for amyloid positivity in a heterogeneous memory clinic-based cohort.

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Background: Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration.

Objectives: This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid beta 40 (Aβ40), and amyloid beta 42 (Aβ42) in a large, well-characterized cohort.

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Article Synopsis
  • Early-onset dementia (EOD) has a genetic basis, with whole-exome sequencing (WES) being utilized for screening and gene discovery among affected individuals.
  • In a study of 60 Austrian EOD patients, 20% were found to have likely disease-causing genetic variants, including notable genes like PSEN1 and APP, suggesting a need for further genetic understanding and patient counseling.
  • The research highlights the importance of sharing genetic data and findings to enable collaboration and potentially identify new genetic risk factors in EOD across different patient groups.
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Background And Purpose: Dementia prevalence is increasing, with numbers projected to double by 2050. Risk factors for its development include age and cardiovascular comorbidities, which are found more often in patients with dementia and should be treated properly to improve outcomes. In this case-control study, we analysed a large population-based prescription database to explore the patterns of co-medication in patients with dementia.

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Article Synopsis
  • C9orf72 repeat expansions are linked to neurodegenerative disorders, with unclear thresholds distinguishing normal from pathogenic variants.
  • In a study of 1804 patients and 643 healthy individuals in Austria, the presence of C9orf72 repeat expansions was found in 3.4% of frontotemporal dementia and 0.8% of Alzheimer's disease cases, with carriers experiencing earlier disease onset.
  • Intermediate C9orf72 alleles were associated with specific symptoms, like cerebellar issues and sensory deficits, suggesting they may influence the clinical presentation of dementia.
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Blood-based biomarkers may add a great benefit in detecting the earliest neuropathological changes in patients with Alzheimer's disease (AD). We examined the utility of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) regarding clinical diagnosis and differentiation between amyloid positive and negative patients. To evaluate the practical application of these biomarkers in a routine clinical setting, we conducted this study in a heterogeneous memory-clinic population.

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Background: With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP.

Methods: Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated.

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Objectives: Neurodegeneration in suspected Alzheimer's disease can be determined using visual rating or quantitative volumetric assessments. We examined the feasibility of volumetric measurements of gray matter (GMV) and hippocampal volume (HCV) and compared their diagnostic performance with visual rating scales in academic and non-academic memory clinics.

Materials And Methods: We included 231 patients attending local memory clinics (LMC) in the Netherlands and 501 of the academic Amsterdam Dementia Cohort (ADC).

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The COVID-19 pandemic led to unprecedented restrictions on social contacts and mobility. Memory clinic patients were disproportionately affected when care was disrupted and routines were abruptly changed. This trial was designed as a pragmatic, prospective, observational study to evaluate the effects of lockdown on memory clinic patients.

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The generation of harmful reactive oxygen species (ROS), including hydrogen peroxide, in out-of-hospital cardiac arrest (OHCA) survivors causes systemic ischemia/reperfusion injury that may lead to multiple organ dysfunction and mortality. We hypothesized that the antioxidant enzyme catalase may attenuate these pathophysiological processes after cardiac arrest. Therefore, we aimed to analyze the predictive value of catalase levels for mortality in OHCA survivors.

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Background: Continuous advances in resuscitation care have increased survival, but the rate of favorable neurological outcome remains low. We have shown the usefulness of proteomics in identifying novel biomarkers to predict neurological outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker.

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Background: The myocardium exhibits an adaptive tissue-specific renin-angiotensin system (RAS), and local dysbalance may circumvent the desired effects of pharmacologic RAS inhibition, a mainstay of heart failure with reduced ejection fraction (HFrEF) therapy.

Objectives: This study sought to investigate human myocardial tissue RAS regulation of the failing heart in the light of current therapy.

Methods: Fifty-two end-stage HFrEF patients undergoing heart transplantation (no RAS inhibitor: n = 9; angiotensin-converting enzyme [ACE] inhibitor: n = 28; angiotensin receptor blocker [ARB]: n = 8; angiotensin receptor neprilysin-inhibitor [ARNi]: n = 7) were enrolled.

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Background: Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular disease (CVD) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of the ESC/EASD risk model in comparison to the Systematic COronary Risk Evaluation (SCORE) risk model and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected cohort of type 2 diabetes mellitus (T2DM).

Methods And Results: A total of 1690 T2DM patients with a 10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations were analyzed.

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Serum neurofilament light chain (sNfL) and its ability to expose axonal damage in neurologic disorders have solicited a considerable amount of attention in blood biomarker research. Hence, with the proliferation of high-throughput assay technology, there is an imminent need to study the pre-analytical stability of this biomarker. We recruited 20 patients with common neurological diagnoses and 10 controls (i.

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Hypoxic-ischemic brain injury can affect and disturb the autonomous nervous system (ANS), which regulates various visceral systems including the gastro-intestinal and emetic system. The present study aimed to analyze the predictive value of gastric regurgitation (GReg) for neurological outcome in out-of-hospital cardiac arrest (OHCA) survivors. In this prospective, single-center study, 79 OHCA survivors treated at a university-affiliated tertiary care centre were included and GReg was measured at the first day after successful cardiopulmonary resuscitation.

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Background: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin () gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory.

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Introduction: Dementia is a leading and growing cause of morbidity and mortality. The aim of this study was to investigate real-world prescription patterns of antidementive medication in one of the largest cohorts published thus far to optimize use in this growing population.

Methods: Prescription claims from 2005 to 2016 were provided by Austrian sickness funds, covering 98% of the population of Austria.

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Background: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients.

Methods: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart.

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