Cerebral Hemodynamic Impairment and Cognitive Dysfunction in APOE4 Carriers With Asymptomatic Carotid Artery Stenosis/Occlusion

• Published in: Journal of the American Heart Association Vol. 14; no. 6; p. e039210
• Main Authors: Kakino, Yoshinori, Hattori, Yorito, Ogata, Soshiro, Nakaoku, Yuriko, Nishimura, Kunihiro, Iida, Hidehiro, Ihara, Masafumi
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 18.03.2025; Wiley
• Subjects: Aged; APOE4; Apolipoprotein E4 - genetics; Asymptomatic Diseases; carotid artery occlusion; carotid artery stenosis; Carotid Stenosis - complications; Carotid Stenosis - diagnosis; Carotid Stenosis - diagnostic imaging; Carotid Stenosis - genetics; Carotid Stenosis - physiopathology; Carotid Stenosis - psychology; cerebral blood flow; Cerebrovascular Circulation - physiology; Cognition; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Cognitive Dysfunction - genetics; Cognitive Dysfunction - physiopathology; Cross-Sectional Studies; Female; Hemodynamics; Heterozygote; Humans; Male; memory; Middle Aged; Original Research; Positron-Emission Tomography; Risk Factors; cerebral blood flow; carotid artery stenosis; memory; APOE4; carotid artery occlusion
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.124.039210

Our previous preclinical study demonstrated that -targeted replacement mice exhibit more severe cerebral hypoperfusion and cognitive impairment than -targeted replacement mice with carotid artery stenosis due to neurovascular dysfunction. Therefore, we clinically investigate whether contributes to cerebral hemodynamic and cognitive impairment in subjects with asymptomatic carotid artery stenosis or occlusion. A cross-sectional observational study was conducted between January 2017 and March 2022. In a primary analysis, 91 subjects (114 affected cerebral hemispheres) with asymptomatic carotid artery stenosis or occlusion who underwent neuropsychological examinations and O-gas positron emission tomography were included to examine associations of with cognitive impairment and cerebral hemodynamic impairment. A sensitivity analysis was performed with 161 subjects (201 affected cerebral hemispheres) who underwent O-gas positron emission tomography scan. In the primary analysis, 20 (22.0%) subjects were carriers. was an independent risk factor of lower cerebral blood flow in the anterior circulation territory (β=-0.058 [95% CI, -0.098 to -0.018], =0.005) and short-term memory impairment in Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (β=1.16 [95% CI, 0.009-2.30], =0.048) in a multivariable linear regression analysis. In the sensitivity analysis, 31 (19.3%) subjects carried , which was an independent risk factor of lower cerebral blood flow (β=-0.048 [95% CI, -0.079 to -0.012], =0.003) in the anterior circulation territory. may confer an increased risk of decreased cerebral blood flow accompanied by memory impairment in asymptomatic carotid artery stenosis or occlusion consistent with our experimental study. genotyping in such subjects may be useful for early detection of disease severity.