{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:44:43Z","timestamp":1756385083647,"version":"3.41.2"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,11,21]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small\u2010vessel disease. Phenotype variability in CADASIL suggests the possible role of genetic modifiers. We aimed to investigate the contributions of the\n              <jats:italic>APOE<\/jats:italic>\n              genotype and Neurogenic locus notch homolog protein 3 (\n              <jats:italic>NOTCH3<\/jats:italic>\n              ) variant position to cognitive impairment associated with CADASIL.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Patients with the cysteine\u2010altering\n              <jats:italic>NOTCH3<\/jats:italic>\n              variant were enrolled in a cross\u2010sectional study, including the Mini\u2010Mental State Examination (MMSE), brain magnetic resonance imaging, and\n              <jats:italic>APOE<\/jats:italic>\n              genotyping. Cognitive impairment was defined as an MMSE score &lt;24. The associations between the MMSE score and genetic factors were assessed using linear regression models. Bayesian adjustment for confounding was used to identify clinical confounders. A total of 246 individuals were enrolled, among whom 210 (85%) harbored the p.R544C variant, 96 (39%) had cognitive impairment, and 150 (61%) had a history of stroke. The\n              <jats:italic>APOE<\/jats:italic>\n              \u025b2 allele was associated with a lower MMSE score (adjusted\n              <jats:italic>B<\/jats:italic>\n              , \u22124.090 [95% CI, \u22126.708 to \u22121.473];\n              <jats:italic>P<\/jats:italic>\n              =0.023), whereas the\n              <jats:italic>NOTCH3<\/jats:italic>\n              p.R544C variant was associated with a higher MMSE score (adjusted\n              <jats:italic>B<\/jats:italic>\n              , 2.854 [95% CI, 0.603\u20135.105];\n              <jats:italic>P<\/jats:italic>\n              =0.0132) after adjustment for age, education, and history of ischemic stroke. Mediation analysis suggests that the associations between the\n              <jats:italic>APOE<\/jats:italic>\n              \u025b2 allele and MMSE score and between the\n              <jats:italic>NOTCH3<\/jats:italic>\n              p.R544C variant and MMSE score are mediated by mesial temporal atrophy and white matter hyperintensity, respectively.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:italic>APOE<\/jats:italic>\n              genotype may modify cognitive impairment in CADASIL, whereby individuals carrying the\n              <jats:italic>APOE<\/jats:italic>\n              \u025b2 allele may present a more severe cognitive impairment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.032689","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:20:37Z","timestamp":1700475637000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Contribution of the\n            <i>APOE<\/i>\n            Genotype to Cognitive Impairment in Individuals With\n            <i>NOTCH3<\/i>\n            Cysteine\u2010Altering Variants"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-6333","authenticated-orcid":false,"given":"Yu\u2010Wen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-2086","authenticated-orcid":false,"given":"Yi\u2010Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital Taipei Taiwan"},{"name":"Faculty of Medicine, School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-8775","authenticated-orcid":false,"given":"Chih\u2010Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-9070","authenticated-orcid":false,"given":"Chih\u2010Ping","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-2276","authenticated-orcid":false,"given":"Cathy S. 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