Association of age-related spontaneous internal jugular vein reflux with cognitive impairment and incident dementia

Abstract

AbstractBackground and purposeThe vascular aspect of cognitive impairment focuses on cerebral small-vessel disease and arterial circulation. However, it remains unclear whether changes in the venous circulation contribute to cognitive decline. This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia.MethodsThe Tokyo Women’s Medical University Cerebrovascular Disease registry is a prospective observational registry in which patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2022.ResultsAmong 906 patients with an MMSE score ≥ 24 enrolled in the registry, 302 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for age, sex, years of education, risk factors, and MRI findings, including small-vessel disease and medial temporal atrophy, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia (Alzheimer disease: 10, vascular dementia: 1) were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, P= 0.031).ConclusionsSpontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.Clinical Trial Registration:URL:https://www.umin.ac.jp. Unique identifier: UMIN000026671.