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Original Investigation
August 2018

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

Author Affiliations
  • 1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Neuroscience Center, Samsung Medical Center, Seoul, Korea
  • 3Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 4Department of Neurology, Kyung Hee University Hospital, Seoul, Korea
  • 5Department of Neurology, Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do, Korea
  • 6Department of Neurology, Chonbuk National University Medical School and Hospital, Jeonju, Korea
  • 7Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 8Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea
  • 9Departments of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 10Center for Imaging of Neurodegenerative Diseases, University of California, San Francisco
  • 11Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley
  • 12Memory and Aging Center, Department of Neurology, University of California, San Francisco
  • 13Department of Neurology and Center for Neuroscience, University of California, Davis
  • 14Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea
  • 15Department of Clinical Research Design and Evaluation, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea
JAMA Neurol. 2018;75(8):999-1007. doi:10.1001/jamaneurol.2018.0975
Key Points

Question  What is the extent and the role of tau, measured by 18F-AV1451 positron emission tomography, in patients with subcortical vascular cognitive impairment?

Findings  In this cross-sectional study of patients with subcortical vascular cognitive impairment, amyloid-β positivity and cerebral small vessel disease score were each independently associated with increased AV1451 uptake in the medial temporal and inferior temporal regions, respectively. Level of AV1451 uptake mediated the associations of amyloid-ß or cerebral small vessel disease with cognitive impairment.

Meaning  The findings suggest that in subcortical vascular cognitive impairment, both amyloid-β and cerebral small vessel disease are independently associated with increased tau accumulation; furthermore, tau burden played a pivotal role because it was the final common pathway for cognitive impairment in patients with subcortical vascular cognitive impairment.

Abstract

Importance  Amyloid-β (Aβ), 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 Aβ 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 18F-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 during AV1451 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 Aβ was assessed using fluorine 18–labeled (18F) florbetaben positron emission tomography. Tau was measured using 18F-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 Aβ, 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 Aβ-negative SVCI, showed higher AV1451 uptake in the inferior temporal areas compared with normal control individuals. In patients with SVCI, Aβ 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, Aβ 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 Aβ 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.

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