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As single-arm trials (SATs) are increasingly used in pharmaceutical research, the validity of such study designs needs to be critically assessed. We characterize the feasibility of supplementing SATs with real-world data (RWD)-derived external control arms by determining the proportion of SATs on breast cancer and amyotrophic lateral sclerosis (ALS) for which an external control arm based on RWD can be constructed. [...]

AimDrugs with anticholinergic effects are often considered as potentially inappropriate medications, especially for older patients, and deprescribing such drugs may improve cognitive function. The aim was to investigate the effectiveness of counselling on drug risks as part of a multimodal intervention to prevent cognitive decline.MethodsThe AgeWell.de study, a multi-centre, cluster-randomized controlled study, was conducted in 123 German general practices between June 2018 and January 2022. [...]

INTRODUCTIONEffective dementia prevention requires understanding the distribution of modifiable risk factors and identifying high-risk subgroups. We estimated the prevention potential in Germany and identified risk profiles to inform precision public health.METHODSWe analyzed nationally representative data from the 2023 German Aging Survey (n = 4992). [...]

ObjectiveAssess the performance of serum phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL) in predicting risk of cognitive impairment or phenoconversion to dementia in individuals with iRBD.MethodsWe measured serum p-tau217 and NfL levels by electrochemiluminescence across 4 polysomnographically confirmed iRBD cohorts (n = 300), including individuals who phenoconverted to Parkinson's disease (PD) (n = 51), dementia with Lewy bodies (DLB) (n = 22), and multiple system atrophy (MSA) (n = 5).ResultsSerum p-tau217 levels were increased in individuals with iRBD and cognitive impairment (CI) on testing defined as Montreal Cognitive Assessment <26 or subthreshold parkinsonism. p-Tau217 differentiated individuals with iRBD who developed PD with CI (PD-CI) or DLB from PD phenoconverters with normal cognition (area under curve [AUC] = 0.82; 95% confidence interval, 0.70–0.93) and from iRBD non-phenoconverters with normal cognition (AUC = 0.83; 95% confidence interval, 0.77–0.89) [...]

BackgroundDigital-motor outcomes promise better responsiveness than clinician-reported outcomes in ataxia trials. However, their patient meaningfulness and sensitivity to change remain to be demonstrated, particularly in the upper limb domain.ObjectivesValidation of quantitative motor (Q-Motor) assessment for upper limb ataxia against patient-reported outcomes and regarding sensitivity to both longitudinal and treatment-induced change, the latter in n-of-1 treatment settings.MethodsSingle-center longitudinal assessment of finger tapping, diadochokinesia, grip-lift, spiral drawing, and target reaching in (1) 36 cross-genotype ataxia patients and 20 controls, validating digital measures for correlations with patient-reported outcome measure (PROM)-ataxia, 2-weeks test–retest reliability, and sensitivity to change within a trial-relevant 1-year follow-up, anchored in Patient Global Impression of Change (PGI-C); and (2) two patients with spinocerebellar ataxia type 27B (SCA27B) on versus off treatment with 4-aminopyridine.ResultsTwenty-four digital measures correlated with the PROM-ataxia upper-limb composite (|ρ| = 0.4–0.7) and had excellent test–retest reliability (ICC = 0.91–0.99). [...]

BackgroundSkin biopsies and seed amplification assays (SAA) provide a sensitive and potentially quantitative method to detect alpha-synuclein (a-syn) aggregation in peripheral nerve fibers in Parkinson's disease (PD). Relating to the previously published hypothesis that PD may either originate in the peripheral (body-first) or central (brain-first) nervous system, we investigated whether patients with clinical features that have been reported to be associated with a suspected body-first subtype of PD exhibit higher levels of a-syn aggregation in dermal nerve fibers compared to those without these features. [...]

Alpha-synuclein (aSyn) is an intrinsically disordered protein involved in phase separation and several age-associated neurodegenerative disorders, including Parkinson's disease. However, its function and pathological role remain elusive. [...]

Neural circuits undergo experience-dependent plasticity to form long-lasting memories, but how inhibitory interneurons contribute to this process remains poorly understood. Using miniature microscope calcium imaging, we monitored the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction. [...]

Somatostatin-receptor (SSTR)-targeting PET/CT is widely used for diagnosis and disease monitoring of pheochromocytoma / paraganglioma (PPGL). The aim of this study was to assess the potential of the novel SSTR-targeting tracer [18F]SiTATE in diagnosing PPGL by comparing imaging parameters to tumor marker levels and secretory activity in a small cohort of patients diagnosed with this rare tumor type.This retrospective study included 34 patients with histologically confirmed PPGL who underwent [18F]SiTATE-PET/CT at LMU University Hospital Munich between 10/2020 and 02/2024 as well as hormonal laboratory analysis within up to 100 days. [...]