TY - JOUR
T1 - Hippocampal and Clinical Trajectories of Mild Cognitive Impairment with Suspected Non-Alzheimer's Disease Pathology
AU - Chung, Jun Ku
AU - Plitman, Eric
AU - Nakajima, Shinichiro
AU - Caravaggio, Fernando
AU - Iwata, Yusuke
AU - Gerretsen, Philip
AU - Kim, Julia
AU - Takeuchi, Hiroyoshi
AU - Shinagawa, Shunichiro
AU - Patel, Raihaan
AU - Chakravarty, M. Mallar
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01AG024904) andDODADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNIdata are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Publisher Copyright:
© 2017 - IOS Press and the authors. All rights reserved.
PY - 2017
Y1 - 2017
N2 - Suspected non-Alzheimer's disease pathology (SNAP) characterizes individuals showing neurodegeneration (e.g., hypometabolism) without amyloid-β (Aβ). Findings from previous studies regarding clinical and structural trajectories of SNAP are inconsistent. Using data from the Alzheimer's Disease Neuroimaging Initiative, patients with amnestic mild cognitive impairment (MCI) were categorized into four groups: amyloid positive with hypometabolism (AβND), amyloid only (AβND-), neither amyloid nor hypometabolism (Aβ-ND-), and SNAP (Aβ-ND). AβND(n=33), AβND-(n=32), and Aβ-ND-(n=36) were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and scores on the Montreal Cognitive Assessment. Elderly controls (n=40) were also matched to SNAP for age, gender, and apoE4 genotype. Longitudinal changes were compared across groups in terms of hippocampal volume, clinical symptoms, daily functioning, and cognitive functioning over a 2-year period. At baseline, no difference in cognition and functioning was observed between SNAP and Aβgroups. SNAP showed worse clinical symptoms and impaired functioning at baseline compared to Aβ-ND-and controls. Two years of follow-up showed no differences in hippocampal volume changes between SNAP and any of the comparison groups. SNAP showed worse functional deterioration in comparison to Aβ-ND-and controls. However, AβND showed more severe changes in clinical symptoms in comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe functional deterioration compared to Aβ-ND-and controls, 2) no differences with AβND-, and 3) less cognitive deterioration than AβND. Future studies should investigate what causes SNAP, which is different from typical AD pathology and biomarker cascades.
AB - Suspected non-Alzheimer's disease pathology (SNAP) characterizes individuals showing neurodegeneration (e.g., hypometabolism) without amyloid-β (Aβ). Findings from previous studies regarding clinical and structural trajectories of SNAP are inconsistent. Using data from the Alzheimer's Disease Neuroimaging Initiative, patients with amnestic mild cognitive impairment (MCI) were categorized into four groups: amyloid positive with hypometabolism (AβND), amyloid only (AβND-), neither amyloid nor hypometabolism (Aβ-ND-), and SNAP (Aβ-ND). AβND(n=33), AβND-(n=32), and Aβ-ND-(n=36) were matched to SNAP for age, gender, apolipoprotein E4 (apoE4) genotype, and scores on the Montreal Cognitive Assessment. Elderly controls (n=40) were also matched to SNAP for age, gender, and apoE4 genotype. Longitudinal changes were compared across groups in terms of hippocampal volume, clinical symptoms, daily functioning, and cognitive functioning over a 2-year period. At baseline, no difference in cognition and functioning was observed between SNAP and Aβgroups. SNAP showed worse clinical symptoms and impaired functioning at baseline compared to Aβ-ND-and controls. Two years of follow-up showed no differences in hippocampal volume changes between SNAP and any of the comparison groups. SNAP showed worse functional deterioration in comparison to Aβ-ND-and controls. However, AβND showed more severe changes in clinical symptoms in comparison to SNAP. Thus, patients with MCI and SNAP showed 1) more severe functional deterioration compared to Aβ-ND-and controls, 2) no differences with AβND-, and 3) less cognitive deterioration than AβND. Future studies should investigate what causes SNAP, which is different from typical AD pathology and biomarker cascades.
KW - Functional decline
KW - hippocampus
KW - mild cognitive impairment
KW - suspected non-Alzheimer's pathology
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UR - http://www.scopus.com/inward/citedby.url?scp=85020378070&partnerID=8YFLogxK
U2 - 10.3233/JAD-170201
DO - 10.3233/JAD-170201
M3 - Article
C2 - 28505977
AN - SCOPUS:85020378070
VL - 58
SP - 747
EP - 762
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -