TY - JOUR
T1 - Amyloid involvement in subcortical regions predicts cognitive decline
AU - For the Alzheimer’s Disease Neuroimaging Initiative
AU - Cho, Soo Hyun
AU - Shin, Jeong Hyeon
AU - Jang, Hyemin
AU - Park, Seongbeom
AU - Kim, Hee Jin
AU - Kim, Si Eun
AU - Kim, Seung Joo
AU - Kim, Yeshin
AU - Lee, Jin San
AU - Na, Duk L.
AU - Lockhart, Samuel N.
AU - Rabinovici, Gil D.
AU - Seong, Joon Kyung
AU - Seo, Sang Won
N1 - Funding Information:
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.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
KW - Alzheimer’s dementia
KW - Amyloid PET
KW - Amyloid staging
KW - Thal staging
UR - http://www.scopus.com/inward/record.url?scp=85049569567&partnerID=8YFLogxK
U2 - 10.1007/s00259-018-4081-5
DO - 10.1007/s00259-018-4081-5
M3 - Article
C2 - 29980831
AN - SCOPUS:85049569567
VL - 45
SP - 2368
EP - 2376
JO - European Journal of Nuclear Medicine
JF - European Journal of Nuclear Medicine
SN - 1619-7070
IS - 13
ER -