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Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients

  • Hyemin Jang
  • Hee Jin Kim
  • Seongbeom Park
  • Yu Hyun Park
  • Yeongsim Choe
  • Hanna Cho
  • Chul Hyoung Lyoo
  • Uicheul Yoon
  • Jin San Lee
  • Yeshin Kim
  • Seung Joo Kim
  • Jun Pyo Kim
  • Young Hee Jung
  • Young Hoon Ryu
  • Jae Yong Choi
  • Seung Hwan Moon
  • Joon-Kyung Seong
  • Charles DeCarli
  • Michael W. Weiner
  • Samuel N. Lockhart
  • Soo Hyun Cho
  • Duk L. Na
  • Sang Won SeoEmail author
Original Article
Part of the following topical collections:
  1. Neurology

Abstract

Objective

To apply an AT (Aβ/tau) classification system to subcortical vascular cognitive impairment (SVCI) patients following recently developed biomarker-based criteria of Alzheimer’s disease (AD), and to investigate its clinical significance.

Methods

We recruited 60 SVCI patients who underwent the neuropsychological tests, brain MRI, and 18F-florbetaben and 18F-AV1451 PET at baseline. As a control group, we further recruited 27 patients with AD cognitive impairment (ADCI; eight Aβ PET-positive AD dementia and 19 amnestic mild cognitive impairment). ADCI and SVCI patients were classified as having normal or abnormal Aβ (A−/A+) and tau (T−/T+) based on PET results. Across the three SVCI groups (A−, A+T−, and A+T+SVCI), we compared longitudinal changes in cognition, hippocampal volume (HV), and cortical thickness using linear mixed models.

Results

Among SVCI patients, 33 (55%), 20 (33.3%), and seven (11.7%) patients were A−, A+T−, and A+T+, respectively. The frequency of T+ was lower in A+SVCI (7/27, 25.9%) than in A+ADCI (14/20, 70.0%, p = 0.003) which suggested that cerebral small vessel disease affected cognitive impairments independently of A+. A+T−SVCI had steeper cognitive decline than A−SVCI. A+T+SVCI also showed steeper cognitive decline than A+T−SVCI. Also, A+T−SVCI had steeper decrease in HV than A−SVCI, while cortical thinning did not differ between the two groups. A+T+SVCI had greater global cortical thinning compared with A+T−SVCI, while declines in HV did not differ between the two groups.

Conclusion

This study showed that the AT system successfully characterized SVCI patients, suggesting that the AT system may be usefully applied in a research framework for clinically diagnosed SVCI.

Keywords

Amyloid-β Tau Classification Subcortical vascular cognitive impairment Longitudinal changes 

Abbreviations

Amyloid-β

SVCI

Subcortical vascular cognitive impairment

HV

Hippocampal volume

AD

Alzheimer’s disease

NIA-AA

National Institute on Aging and Alzheimer’s Association

PET

Positron emission tomography

CSF

Cerebrospinal fluid

CSVD

Cerebral small vessel disease

MCI

Mild cognitive impairment

ADCI

Alzheimer’s disease–related cognitive impairment

WMH

White matter hyperintensities

MRI

Magnetic resonance imaging

NC

Normal control

ADD

Alzheimer’s disease dementia

SUVR

Standardized uptake value ratios

ROI

Region of interest

PVE

Partial volume effect

FLAIR

Fluid-attenuated inversion recovery

GRE

Gradient echo

CMBs

Cerebral microbleeds

BAPL

Brain Aβ plaque load

SNSB

Seoul Neuropsychological Screening Battery

SVLT

Seoul Verbal Learning Test

RCFT

Rey–Osterrieth Complex Figure Test

KBNT

Korean version of the Boston Naming Test

MMSE

Mini-Mental State Examination

CDR-SB

Clinical Dementia Rating sum of boxes

ICV

Intracranial volume

ANOVA

Analysis of variance

ANCOVA

Analysis of covariance

Notes

Funding information

This research was supported by funds (2018-ER6202-01) from Research of Korea Centers for Disease Control and Prevention; the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1913844); NRF grant funded by the Korea government (2017R1A2B2005081)

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Role of the funder

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2019_4498_MOESM1_ESM.docx (34 kb)
ESM 1 (DOCX 34 kb).
259_2019_4498_MOESM2_ESM.docx (35 kb)
ESM 2 (DOCX 35 kb).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hyemin Jang
    • 1
    • 2
  • Hee Jin Kim
    • 1
    • 2
  • Seongbeom Park
    • 1
    • 2
  • Yu Hyun Park
    • 1
    • 2
  • Yeongsim Choe
    • 1
    • 2
  • Hanna Cho
    • 4
  • Chul Hyoung Lyoo
    • 4
  • Uicheul Yoon
    • 5
  • Jin San Lee
    • 6
  • Yeshin Kim
    • 7
  • Seung Joo Kim
    • 1
    • 2
  • Jun Pyo Kim
    • 1
    • 2
  • Young Hee Jung
    • 1
    • 2
  • Young Hoon Ryu
    • 8
  • Jae Yong Choi
    • 9
  • Seung Hwan Moon
    • 10
  • Joon-Kyung Seong
    • 11
  • Charles DeCarli
    • 12
  • Michael W. Weiner
    • 3
  • Samuel N. Lockhart
    • 13
  • Soo Hyun Cho
    • 14
  • Duk L. Na
    • 1
    • 2
    • 15
    • 16
  • Sang Won Seo
    • 1
    • 2
    • 16
    • 17
    • 18
    Email author
  1. 1.Department of Neurology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Neuroscience CenterSamsung Medical CenterSeoulSouth Korea
  3. 3.Center for Imaging of Neurodegenerative DiseasesUniversity of California, San FranciscoSan FranciscoUSA
  4. 4.Department of Neurology, Gangnam Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  5. 5.Department of Biomedical Engineering, College of Health and Medical ScienceCatholic University of DaeguGyeongsanSouth Korea
  6. 6.Department of NeurologyKyung Hee University HospitalSeoulSouth Korea
  7. 7.Department of Neurology, Kangwon National University HospitalKangwon National University College of MedicineChuncheonSouth Korea
  8. 8.Department of Nuclear Medicine, Gangnam Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  9. 9.Division of RI-Convergence ResearchKorea Institute Radiological and Medical SciencesSeoulSouth Korea
  10. 10.Departments of Nuclear Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  11. 11.School of Biomedical EngineeringKorea UniversitySeoulSouth Korea
  12. 12.Department of Neurology and Center for NeuroscienceUniversity of California, DavisDavisUSA
  13. 13.Department of Internal MedicineWake Forest School of MedicineWinston-SalemUSA
  14. 14.Department of NeurologyChonnam National University HospitalGwangjuSouth Korea
  15. 15.Department of Health Sciences and Technology, SAIHSTSungkyunkwan UniversitySeoulSouth Korea
  16. 16.Samsung Alzheimer Research CenterSamsung Medical CenterSeoulSouth Korea
  17. 17.Department of Clinical Research Design and Evaluation, SAIHSTSungkyunkwan UniversitySeoulSouth Korea
  18. 18.Center for Clinical EpidemiologySamsung Medical CenterSeoulSouth Korea

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