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Amyloid involvement in subcortical regions predicts cognitive decline

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We estimated whether amyloid involvement in subcortical regions may predict cognitive impairment, and established an amyloid staging scheme based on degree of subcortical amyloid involvement.

Methods

Data from 240 cognitively normal older individuals, 393 participants with mild cognitive impairment, and 126 participants with Alzheimer disease were acquired at Alzheimer’s Disease Neuroimaging Initiative sites. To assess subcortical involvement, we analyzed amyloid deposition in amygdala, putamen, and caudate nucleus. We staged participants into a 3-stage model based on cortical and subcortical amyloid involvement: 382 with no cortical or subcortical involvement as stage 0, 165 with cortical but no subcortical involvement as stage 1, and 203 with both cortical and subcortical involvement as stage 2.

Results

Amyloid accumulation was first observed in cortical regions and spread down to the putamen, caudate nucleus, and amygdala. In longitudinal analysis, changes in MMSE, ADAS-cog 13, FDG PET SUVR, and hippocampal volumes were steepest in stage 2 followed by stage 1 then stage 0 (p value <0.001). Stage 2 showed steeper changes in MMSE score (β [SE] = −0.02 [0.004], p < 0.001), ADAS-cog 13 (0.05 [0.01], p < 0.001), FDG PET SUVR (−0.0008 [0.0003], p = 0.004), and hippocampal volumes (−4.46 [0.65], p < 0.001) compared to stage 1.

Conclusions

We demonstrated a downward spreading pattern of amyloid, suggesting that amyloid accumulates first in neocortex followed by subcortical structures. Furthermore, our new finding suggested that an amyloid staging scheme based on subcortical involvement might reveal how differential regional accumulation of amyloid affects cognitive decline through functional and structural changes of the brain.

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Funding

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2017R1A2B2005081 and No. 2016R1A2B4014398) and National Institutes of Health (NIH) grant P30AG049638.

Author information

Author notes

  1. Soo Hyun Cho and Jeong-Hyeon Shin contributed equally to this article as co-first authors.

  2. Joon-Kyung Seong and Sang Won Seo contributed equally to this article as co-corresponding authors.

Authors and Affiliations

  1. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Soo Hyun Cho, Hyemin Jang, Seongbeom Park, Hee Jin Kim, Si Eun Kim, Seung Joo Kim, Yeshin Kim, Duk L. Na & Sang Won Seo

  2. Neuroscience Center, Samsung Medical Center, Seoul, South Korea

    Soo Hyun Cho, Hyemin Jang, Seongbeom Park, Hee Jin Kim, Si Eun Kim, Seung Joo Kim, Yeshin Kim, Duk L. Na & Sang Won Seo

  3. School of Biomedical Engineering, Korea University, Seoul, Republic of Korea

    Jeong-Hyeon Shin & Joon-Kyung Seong

  4. Department of Neurology, Kyung Hee University Hospital, Seoul, South Korea

    Jin San Lee

  5. Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea

    Duk L. Na

  6. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Duk L. Na & Sang Won Seo

  7. Internal Medicine - Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA

    Samuel N. Lockhart

  8. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

    Gil D. Rabinovici

  9. Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea

    Sang Won Seo

Authors
  1. Soo Hyun Cho
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  2. Jeong-Hyeon Shin
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  8. Yeshin Kim
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  9. Jin San Lee
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  10. Duk L. Na
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  11. Samuel N. Lockhart
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  12. Gil D. Rabinovici
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  13. Joon-Kyung Seong
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  14. Sang Won Seo
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Consortia

For the Alzheimer’s Disease Neuroimaging Initiative

Contributions

S.H.C., J.H.S., J.K.S. and S.W.S. contributed to the conceptualization of the study, analysis and interpretation of data, and drafting. J.H.S. and S.P contributed to analyses of imaging data, prepared the figures, and provided technical support. H.J.K., H.M.J., S.E.K., S.J.K., Y.K. and J.S.L. contributed to interpretation of data. S.L., G.D.R. and D.L.N. contributed to analysis and interpretation of data.

Corresponding authors

Correspondence to Joon-Kyung Seong or Sang Won Seo.

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Conflict of interest

All authors have no conflicts of interest to disclose.

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.

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Cho, S.H., Shin, JH., Jang, H. et al. Amyloid involvement in subcortical regions predicts cognitive decline. Eur J Nucl Med Mol Imaging 45, 2368–2376 (2018). https://doi.org/10.1007/s00259-018-4081-5

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  • DOI: https://doi.org/10.1007/s00259-018-4081-5

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