Cerebral Small Vessel Disease (cSVD) of ischemic type, either sporadic or genetic, as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), can impact the quality of daily life on various cognitive, motor, emotional or behavioral aspects. No instrument has been developed to measure these outcomes from the patient's perspective. We thus aimed to develop and validate a patient-reported questionnaire. Methods In a development study, 79 items were generated by consensus between patients, family representatives and cSVD experts. A first sample of patients allowed assessing the feasibility (missing data, floor and ceiling effect, acceptability), internal consistency, and dimensionality of a first set of items. Thereafter, in a validation study, we tested a reduced version of the item set in a larger sample to assess the feasibility, internal consistency, dimensionality, test-retest reliability, concurrent validity, and sensitivity to change.

The scale was developed in 44 cSVD patients and validated in a second sample of 89 individuals (including 43 patients with CADASIL and 46 with another cSVD). The final CADASIL Patient-Reported Outcome (CADA-PRO) scale comprised 18 items covering four categories of consequences (depression/anxiety, attention/executive functions, motor, daily activities) of the disease. The proportion of missing data was low, no item displayed major floor or ceiling effect. Both the internal consistency and test-retest reliability were good (Cronbach alpha=0.95, intraclass correlation coefficient=0.88). In patients with CADASIL, CADA-PRO scores correlated with the modified Rankin scale, Starkstein Apathy Scale (SAS), Hospital Anxiety and Depression scale (HAD), Working Memory Index, and Trail Making Test times. In patients with other cSVDs, CADA-PRO correlated only with HAD and SAS.

The CADA-PRO may be an innovative instrument for measuring patient-reported outcomes in future cSVD trials. Full validation was obtained for its use in CADASIL patients, but further improvement is needed for its application in other cSVDs.