Samancı, Bedia

Abstract Background Identification of individuals at increased risk for synucleinopathies is becoming more feasible with advances in biomarkers. However, the ethical and practical aspects of communicating disease risk remain unresolved, particularly across diagnostic groups and cultural contexts. Objectives We aimed to evaluate attitudes toward disclosure of future synucleinopathy risk among individuals with isolated/idiopathic REM sleep behavior disorder (iRBD), as well as in individuals who developed Parkinson's disease (PD), or multiple system atrophy (MSA), in a large non‐Western registry. Methods This nationwide survey study included participants from 28 movement disorders and sleep centers across Türkiye. Questionnaires assessing attitudes toward risk disclosure, additional testing, and clinical trial participation were administered face‐to‐face. Responses were analyzed using contingency tables and regression models. Results are reported following the Consensus‐Based Checklist for Reporting of Survey Studies (CROSS) guideline. Results Among 1385 participants (1039 PD, 107 MSA, 239 iRBD), individuals with iRBD showed the highest support for risk disclosure (88.3%), exceeding PD (64.4%) and MSA (51.9%). Approval declined modestly (3–8%) when framed within the absence of disease‐modifying treatment. iRBD participants were more willing for additional testing but less willing to join clinical trials (31.8%) than PD (45.3%) or MSA (48%). MSA patients expressed the greatest concern about psychological impact. Male sex had more favorable views on disclosure and trial participation, while younger and better‐educated participants favored additional testing. Conclusions Attitudes toward risk disclosure differ markedly across the synucleinopathy spectrum and demographic characteristics. Culturally informed and diagnosis‐specific disclosure strategies will be essential for trial recruitment and patient‐centered care.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

Abstract INTRODUCTION Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word‐finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face‐recognition deficits (60%). Real‐life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real‐life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.