Assessment of Extent and Role of Tau in Subcortical Vascular Cognitive Impairment Using F-18-AV1451 Positron Emission Tomography Imaging

IMPORTANCE Amyioid-beta (A beta), tau, and cerebral small vessel disease (CSVD), which occasionally coexist, are the most common causes of cognitive impairments in older people. However, whether tau is observed in patients with subcortical vascular cognitive impairment (SVCI), as well as its associations with A beta and CSVD, are not yet established. More importantly, the role of tau underlying cognitive impairments in SVCI is unknown. OBJECTIVE To investigate the extent and the role of tau in patients with SVCI using F-18-AV1451, which is a new ligand to detect neurofibrillary tangles in vivo. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study recruited 64 patients with SVCI from June 2015 to December 2016 at Samsung Medical Center, Seoul, Korea. The patients had significant ischemia on brain magnetic resonance imaging, defined as periventricular white matter hyperintensity at least 10 mm and deep white matter hyperintensity at least 25 mm. We excluded 3 patients with SVCI owing to segmentation error duringAV1451 positron emission tomography analysis. MAIN OUTCOMES AND MEASURES We calculated CSVD scores based on the volumes of white matter hyperintensities, numbers of lacunes, and microbleeds using magnetic resonance imaging data. The presence of A beta was assessed using fluorine 18-labeled (F-18)florbetaben positron emission tomography. Tau was measured using(18)F-AV1451 positron emission tomography. We determined the spreading order of tau by sorting the regional frequencies of cortical involvement. We evaluated the complex associations between A beta, CSVD, AV1451 uptake, and cognition in patients with SVCI. RESULTS Of the 61 patients with SVCI, 44 (72.1%) were women and the mean (SD) age was 78 7 (6.3) years. Patients with SVCI, especially patients with A beta-negative SVCI, showed higher AV1451 uptake in the inferior temporal areas compared with normal control individuals. In patients with SVCI, A beta positivity and CSVD score were each independently associated with increased AV1451 uptake in the medial temporal and inferior temporal regions, respectively. Involvement frequency of AV1451 uptake in the fusiform gyrus, inferior temporal, and precuneus regions were higher than that in the parahippocampal region. In patients with SVCI, higher AV1451 uptake in the inferior temporal and medial temporal regions correlated with worse language and general cognitive function. In patients with SVCI, A beta positivity and CSVD score each correlated with worse general cognitive function, which was completely mediated by AV1451 uptake in the entorhinal cortex and inferior temporal gyrus, respectively. CONCLUSIONS AND RELEVANCE Our findings suggest that in SVCI, both A beta and CSVD were independently associated with increased tau accumulation. Furthermore, tau burden played a pivotal role because it was the final common pathway for the cognitive impairment in patients with SVCI.