Defining patient-reported outcomes and priorities for clinical trials in CADASIL through an international survey

IF 2.8 Q3 CLINICAL NEUROLOGY

Cerebral circulation - cognition and behavior Pub Date : 2026-01-01 Epub Date: 2026-02-20 DOI:10.1016/j.cccb.2026.100534

Nikolaos Karvelas , Sheila Connor , Andria Burroso , Ki Coale , Mariana Lemos Duarte , Yuguang Xiong , Liqhwa Ncube , Claudia Kunney , Debarag Banerjee , Michael Kennedy , Sarah McDaniels , Pedro de Lencastre , Jane Gunther , Bert Kasiske , Fanny M. Elahi

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Abstract

Background

A major challenge faced by clinical trials for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the heterogeneity of symptoms and variable progression pace, while treatments should attenuate symptoms that bother patients most. To this end, we set to describe the symptomatic landscape for CADASIL with the ultimate goal of developing Patient Reported Outcomes (PRO) for clinical trials.

Methods

A survey was compiled through iterative consensus meetings between patients, family members, CADASIL clinicians, and patient advocacy group members (cureCADASIL). The final questionnaire included demographic information, subjective symptom severity ratings, medication use and lifestyle factors. Data were collected over a period of 16 months from 11/2023 to 3/2025 and analyzed through descriptive and quantitative methods.

Results

We collected 226 responses from 25 countries. The average age of responders was 52 (SD 12) years, and 158 (69.9 %) identified as women. Out of all symptoms, fatigue was reported as the most frequent (86.3 %), and most bothersome (14.2 %). Symptom severity differed across age groups only for headaches, with younger participants reporting higher scores (Kruskal–Wallis χ² = 8.64, p = 0.03). All symptoms were intercorrelated, with strongest clustering among congruent categories such as slowed thinking, cognitive fog, and memory complaints (Spearman’s ρ ≥ 0.70, adjusted p < 0.001). Medication use was widespread: 156 participants (69 %) reported prescription medications, 116 (51.3 %) over-the-counter drugs, and 128 (56.6 %) supplements.

Conclusions

By identifying symptom domains most salient to patients, our study provides a foundation for the development of PRO tools in CADASIL.

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通过一项国际调查确定患者报告的CADASIL临床试验的结果和优先级。

背景：脑常染色体显性动脉病变伴皮质下梗死和脑白质病（CADASIL）临床试验面临的主要挑战是症状的异质性和进展速度的变化，而治疗应减轻最困扰患者的症状。为此，我们开始描述CADASIL的症状景观，最终目标是为临床试验开发患者报告的结果（PRO）。方法：通过患者、家属、CADASIL临床医生和患者倡导小组成员（cureCADASIL）之间的反复共识会议进行调查。最终的问卷调查包括人口统计信息、主观症状严重程度评分、药物使用和生活方式因素。数据收集时间为2023年11月至2025年3月16个月，通过描述性和定量方法进行分析。结果：我们收集了来自25个国家的226份回复。应答者的平均年龄为52岁（SD 12），其中158人（69.9%）为女性。在所有症状中，疲劳是最常见的（86.3%），也是最麻烦的（14.2%）。只有头痛的症状严重程度在不同年龄组之间存在差异，越年轻的参与者报告的分数越高（Kruskal-Wallis χ²= 8.64,p = 0.03）。所有症状都是相互关联的，在思维迟钝、认知模糊和记忆不适等一致的类别中聚类最强（Spearman ρ≥0.70，调整后p < 0.001）。药物使用很普遍：156名参与者（69%）报告服用处方药，116名（51.3%）报告服用非处方药，128名（56.6%）报告服用补充剂。结论：通过识别患者最突出的症状域，我们的研究为CADASIL PRO工具的开发提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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