Apolipoprotein E ε4 Is Associated With the Development of Incident Dementia in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients With p.Arg544Cys Mutation

Jung Seok Lee; Keun Hyuk Ko; Jung-Hwan Oh; Joong-Goo Kim; Chul-Hoo Kang; Sook-Keun Song; Sa-Yoon Kang; Ji-Hoon Kang; Joon Hyuk Park; Myeong Ju Koh; Ho Kyu Lee; Jay Chol Choi

doi:10.3389/fnagi.2020.591879

Apolipoprotein E ε4 Is Associated With the Development of Incident Dementia in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients With p.Arg544Cys Mutation

Front Aging Neurosci. 2020 Nov 20:12:591879. doi: 10.3389/fnagi.2020.591879. eCollection 2020.

Authors

Jung Seok Lee¹, Keun Hyuk Ko², Jung-Hwan Oh¹, Joong-Goo Kim¹, Chul-Hoo Kang³, Sook-Keun Song¹, Sa-Yoon Kang¹, Ji-Hoon Kang¹, Joon Hyuk Park⁴, Myeong Ju Koh⁵, Ho Kyu Lee⁵, Jay Chol Choi^{1

6}

Affiliations

¹ Department of Neurology, Jeju National University, Jeju, South Korea.
² Department of Neurology, Hankook Hospital, Jeju, South Korea.
³ Department of Neurology, Jeju National University Hospital, Jeju, South Korea.
⁴ Department of Psychiatry, Jeju National University, Jeju, South Korea.
⁵ Department of Radiology, Jeju National University, Jeju, South Korea.
⁶ Institute of Medical Science, Jeju National University, Jeju, South Korea.

Abstract

Background and purpose: To identify clinical, laboratory, and magnetic resonance imaging (MRI) features in predicting incident stroke and dementia in Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Materials and methods: We enrolled 87 Korean CADASIL patients who had undergone baseline clinical, laboratory, and MRI examinations between March 2012 and February 2015. The primary outcome of this study is the occurrence of stroke and dementia during the study period. The occurrence of incident stroke was confirmed by neuroimaging study, and dementia was defined by the diagnostic and statistical manual of mental disorders, fourth edition, criteria.

Results: Of the 87 patients, 57.5% were men, and the mean age was 63 ± 13 years (range 34-90 years), and 82 patients (94.3%) had p.Arg544Cys mutation. During an average follow-up of 67 months (interquartile range: 53-69 months), incident stroke occurred in 14 of 87 patients (16.1%) and incident dementia in 7 of 70 non-demented patients (10.0%). In adjusted analysis, increased systolic blood pressure was associated with increased risk of incident stroke [for every 10-mmHg increase; hazard ratio, 1.44 (1.02-2.03)]. Apolipoprotein E ε4 genotype was associated with an increased risk of incident dementia [hazard ratio, 10.70 (1.27-89.88)].

Conclusion: In this study, apolipoprotein E ε4 genotype was associated with the development of incident dementia, and higher blood pressure was associated with increased risk of incident stroke in CADASIL patients with predominant p.Arg544Cys mutation.

Keywords: APOE genotyping; CADASIL; MRI; dementia; stroke.