title: Suspected non-AD pathology in mild cognitive impairment.
abstract: 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.
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: Laura.Wisse@uphs.upenn.edu.
authors.forename: Laura E M
authors.initials: LEM
authors.lastname: Wisse
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nirali
authors.initials: N
authors.lastname: Butala
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sandhitsu R
authors.initials: SR
authors.lastname: Das
authors.affiliation: Section of Biomedical Image Analysis, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Psychiatric Neuroimaging Division, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sanjeev N
authors.initials: SN
authors.lastname: Vaishnavi
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yushkevich
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D003071:Cognition; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D009410:Nerve Degeneration; D059906:Neuroimaging; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Amyloidosis; Cerebrovascular disease; Cognition; Mild cognitive impairment; Primary age-related tauopathy; Suspected non-AD pathology