Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Akira Taniguchi; Akihiro Shindo; Ken-Ichi Tabei; Osamu Onodera; Yukio Ando; Takao Urabe; Kazumi Kimura; Kazuo Kitagawa; Yoshihiro Miyamoto; Misa Takegami; Masafumi Ihara; Ikuko Mizuta; Toshiki Mizuno; Hidekazu Tomimoto

doi:10.3389/fnagi.2022.876437

Imaging Characteristics for Predicting Cognitive Impairment in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Front Aging Neurosci. 2022 Jun 10:14:876437. doi: 10.3389/fnagi.2022.876437. eCollection 2022.

Authors

Akira Taniguchi¹, Akihiro Shindo¹, Ken-Ichi Tabei^{1

2}, Osamu Onodera³, Yukio Ando^{4

5}, Takao Urabe⁶, Kazumi Kimura⁷, Kazuo Kitagawa⁸, Yoshihiro Miyamoto⁹, Misa Takegami¹⁰, Masafumi Ihara¹¹, Ikuko Mizuta¹², Toshiki Mizuno¹², Hidekazu Tomimoto¹

Affiliations

¹ Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan.
² School of Industrial Technology, Advanced Institute of Industrial Technology, Tokyo Metropolitan Public University Corporation, Tokyo, Japan.
³ Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University, Niigata, Japan.
⁴ Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
⁵ Department of Amyloidosis Research, Nagasaki International University, Nagasaki, Japan.
⁶ Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
⁷ Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
⁸ Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
⁹ Open Innovation Center, National Cerebral and Cardiovascular Center, Osaka, Japan.
¹⁰ Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
¹¹ Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
¹² Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract

Objectives: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL.

Methods: Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated.

Results: Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia (p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723-0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719-0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551-0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity.

Conclusion: The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML.

Keywords: CADASIL; cognitive impairment; dementia; lacunar; microbleeds; small vessel disease; white matter.