TY - JOUR
T1 - Suspected non-AD pathology in mild cognitive impairment
AU - Alzheimer's Disease Neuroimaging Initiative
AU - Wisse, Laura E.M.
AU - Butala, Nirali
AU - Das, Sandhitsu R.
AU - Davatzikos, Christos
AU - Dickerson, Bradford C.
AU - Vaishnavi, Sanjeev N.
AU - Yushkevich, Paul A.
AU - Wolk, David A.
N1 - Funding Information:
The study was funded by National Institute on Aging grants: R01 AG037376 , P30 AG010124 , and R01 AG040271 . Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (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: Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; BioClinica, Inc ; Biogen Idec Inc ; Bristol-Myers Squibb Company ; 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 ; Medpace, Inc ; Merck & Co, Inc ; Meso Scale Diagnostics, LLC ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc ; Piramal Imaging ; Servier ; Synarc Inc ; and Takeda Pharmaceutical Company . 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 ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Publisher Copyright:
© 2015 Elsevier Inc..
PY - 2015/12
Y1 - 2015/12
N2 - We aim to better characterize mild cognitive impairment (MCI) patients with suspected non-Alzheimer's disease (AD) pathology (SNAP) based on their longitudinal outcome, cognition, biofluid, and neuroimaging profile. MCI participants (n = 361) from ADNI-GO/2 were designated "amyloid positive" with abnormal amyloid-beta 42 levels (AMY+) and "neurodegeneration positive" (NEU+) with abnormal hippocampal volume or hypometabolism using fluorodeoxyglucose-positron emission tomography. SNAP was compared with the other MCI groups and with AMY- controls. AMY-NEU+/SNAP, 16.6%, were older than the NEU- groups but not AMY- controls. They had a lower conversion rate to AD after 24 months than AMY+NEU+ MCI participants. SNAP-MCI participants had similar amyloid-beta 42 levels, florbetapir and tau levels, but larger white matter hyperintensity volumes than AMY- controls and AMY-NEU- MCI participants. SNAP participants performed worse on all memory domains and on other cognitive domains, than AMY-NEU- participants but less so than AMY+NEU+ participants. Subthreshold levels of cerebral amyloidosis are unlikely to play a role in SNAP-MCI, but pathologies involving the hippocampus and cerebrovascular disease may underlie the neurodegeneration and cognitive impairment in this group.
AB - We aim to better characterize mild cognitive impairment (MCI) patients with suspected non-Alzheimer's disease (AD) pathology (SNAP) based on their longitudinal outcome, cognition, biofluid, and neuroimaging profile. MCI participants (n = 361) from ADNI-GO/2 were designated "amyloid positive" with abnormal amyloid-beta 42 levels (AMY+) and "neurodegeneration positive" (NEU+) with abnormal hippocampal volume or hypometabolism using fluorodeoxyglucose-positron emission tomography. SNAP was compared with the other MCI groups and with AMY- controls. AMY-NEU+/SNAP, 16.6%, were older than the NEU- groups but not AMY- controls. They had a lower conversion rate to AD after 24 months than AMY+NEU+ MCI participants. SNAP-MCI participants had similar amyloid-beta 42 levels, florbetapir and tau levels, but larger white matter hyperintensity volumes than AMY- controls and AMY-NEU- MCI participants. SNAP participants performed worse on all memory domains and on other cognitive domains, than AMY-NEU- participants but less so than AMY+NEU+ participants. Subthreshold levels of cerebral amyloidosis are unlikely to play a role in SNAP-MCI, but pathologies involving the hippocampus and cerebrovascular disease may underlie the neurodegeneration and cognitive impairment in this group.
KW - Amyloidosis
KW - Cerebrovascular disease
KW - Cognition
KW - Mild cognitive impairment
KW - Primary age-related tauopathy
KW - Suspected non-AD pathology
UR - http://www.scopus.com/inward/record.url?scp=84946562079&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946562079&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2015.08.029
DO - 10.1016/j.neurobiolaging.2015.08.029
M3 - Article
C2 - 26422359
AN - SCOPUS:84946562079
SN - 0197-4580
VL - 36
SP - 3152
EP - 3162
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 12
ER -