Suspected non-AD pathology in mild cognitive impairment

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.