Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals
Issued Date
2024-01-01
Resource Type
ISSN
00223050
eISSN
1468330X
Scopus ID
2-s2.0-85214383059
Pubmed ID
39547790
Journal Title
Journal of Neurology, Neurosurgery and Psychiatry
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SCOPUS
Bibliographic Citation
Journal of Neurology, Neurosurgery and Psychiatry (2024)
Suggested Citation
Sukhonpanich N., Koohi F., Jolly A.A., Markus H.S. Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals. Journal of Neurology, Neurosurgery and Psychiatry (2024). doi:10.1136/jnnp-2024-334823 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102704
Title
Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals
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Abstract
Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype is becoming milder with better risk factor treatments and other care improvements is unknown. In a large longitudinal CADASIL cohort, we determined whether the prognosis has changed over 23 years. Methods Patients were identified from the Cambridge CADASIL register and the UK Familial stroke study. Change in age at stroke over the time of recruitment was determined using linear mixed-effects model, and the impact of genetic and vascular risk factors on stroke and dementia risk was further evaluated using Cox proportional hazard regression. Results A total of 555 patients with CADASIL were recruited between 2001 and 2023. The age of stroke onset significantly increased over time (p<0.001), with the mean age of stroke onset for patients recruited before 2016 (n=265) at 46.7±9.2 years and 51.6±9.5 years for those recruited since 2016 (n=290). Patients recruited since 2016 had lower risks of both stroke (HR 0.36, 95% CI 0.26 to 0.50, p<0.001) and dementia (HR 0.43, 95% CI 0.19 to 0.99, p=0.046) after adjusting for sex, hypertension history, smoking status, epidermal growth factor-like repeat position and calendar effect. Conclusions The clinical phenotype of CADASIL is improving. While this may be partly explained by reduced vascular risk factors such as smoking and the identification of milder cases, differences persisted after controlling for risk factors and mutation sites. These updated risk estimates should be used when counselling patients with CADASIL on prognosis.