DOI: 10.1007/s00259-018-4081-5Pages: 2368-2376

Amyloid involvement in subcortical regions predicts cognitive decline

1. Sungkyunkwan University School of Medicine, Department of Neurology, Samsung Medical Center

2. Samsung Medical Center, Neuroscience Center

3. Korea University, School of Biomedical Engineering

4. Kyung Hee University Hospital, Department of Neurology

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

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

7. Wake Forest School of Medicine, Internal Medicine - Gerontology and Geriatric Medicine

8. University of California, Memory and Aging Center, Department of Neurology

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

Correspondence to:
Sang Won Seo
Tel: +82-2-3410-1233




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.


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.


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.


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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  • Accepted: Jun 25, 2018
  • Online: Jul 6, 2018

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