Amyloid involvement in subcortical regions predicts cognitive decline

For the Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
DOIs
Publication statusAccepted/In press - 2018 Jul 6

Fingerprint

Amyloid
Caudate Nucleus
Putamen
Amygdala
Alzheimer Disease
Cognitive Dysfunction
Neocortex
Neuroimaging
Brain

Keywords

  • Alzheimer’s dementia
  • Amyloid PET
  • Amyloid staging
  • Thal staging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Amyloid involvement in subcortical regions predicts cognitive decline. / For the Alzheimer’s Disease Neuroimaging Initiative.

In: European Journal of Nuclear Medicine and Molecular Imaging, 06.07.2018, p. 1-9.

Research output: Contribution to journalArticle

@article{e90809d169cb4302b5bd6051b5b936ca,
title = "Amyloid involvement in subcortical regions predicts cognitive decline",
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.",
keywords = "Alzheimer’s dementia, Amyloid PET, Amyloid staging, Thal staging",
author = "{For the Alzheimer’s Disease Neuroimaging Initiative} and Cho, {Soo Hyun} and Shin, {Jeong Hyeon} and Hyemin Jang and Seongbeom Park and Kim, {Hee Jin} and Kim, {Si Eun} and Kim, {Seung Joo} and Yeshin Kim and Lee, {Jin San} and Na, {Duk L.} and Lockhart, {Samuel N.} and Rabinovici, {Gil D.} and Seong, {Jun Kyung} and Seo, {Sang Won}",
year = "2018",
month = "7",
day = "6",
doi = "10.1007/s00259-018-4081-5",
language = "English",
pages = "1--9",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",

}

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, Jun Kyung

AU - Seo, Sang Won

PY - 2018/7/6

Y1 - 2018/7/6

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

UR - http://www.scopus.com/inward/citedby.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

SP - 1

EP - 9

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

ER -