Suspected non-AD pathology in mild cognitive impairment

• Published in: Neurobiology of aging Vol. 36; no. 12; pp. 3152 - 3162
• Main Authors: Wisse, Laura E.M, Butala, Nirali, Das, Sandhitsu R, Davatzikos, Christos, Dickerson, Bradford C, Vaishnavi, Sanjeev N, Yushkevich, Paul A, Wolk, David A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2015
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Amyloidosis; Cerebrovascular disease; Cognition; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; Cognitive Dysfunction - psychology; Female; Hippocampus - metabolism; Hippocampus - pathology; Humans; Internal Medicine; Male; Memory; Middle Aged; Mild cognitive impairment; Nerve Degeneration; Neuroimaging; Neurology; Peptide Fragments - metabolism; Primary age-related tauopathy; Suspected non-AD pathology; Cognition; Amyloidosis; Suspected non-AD pathology; Primary age-related tauopathy; Mild cognitive impairment; Cerebrovascular disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2015.08.029

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.