O1‐07‐05: Mild cognitive impairment patients with suspected non‐alzheimer's disease pathology
Year: 2015
Type: article
Abstract: The pathophysiological sequence of Alzheimer disease (AD) is posited to start with amyloid deposition, followed by neurodegeneration and then cognitive symptoms. However, a considerable portion of Mild Cognitive Impairment (MCI) patients presents with AD-like neurodegeneration in the absence of amyloid deposition. This group has been referred to as suspected non-AD pathophysiology (SNAP). We aim to better characterize these patients based on their cognition, biofluid and neuroimaging biomarker profile and longitudinal outcome. MCI patients (n=361) with available cerebrospinal fluid (CSF), FDG-PET and MRI data from ADNI2/Go were designated ‘amyloid positive’ (AMY+) if Aβ42 levels were <192 pg/mL and ‘neurodegeneration positive’ (NEU+) if they had abnormal hippocampal volume or displayed hypometabolism using FDG-PET in a meta-ROI associated with AD. Cut-off points for both measures were derived to optimize sensitivity and specificity in discriminating AMY- controls (n=87) from AMY+ AD patients (n=113). Sixty patients (16.6%) were AMY-NEU+, or SNAP (see table); 85% were positive by hippocampal volume and 28% by FDG-PET. SNAP patients were older than AMY-NEU-patients. The prevalence of APOE-ɛ4 was lower than in the AMY+ groups. After 24 months 2% converted to AD, similar to the NEU- groups but less than the AMY+NEU+ group. SNAP patients displayed no difference in CSF Aβ42, florbetapir SUVR, and CSF tau levels compared to AMY-NEU- patients and age-matched AMY- controls. White matter hyperintensity (WMH) volume was higher in SNAP than in AMY-NEU- patients. Moreover, SNAP patients displayed poorer memory, but also poorer performance in other domains, than AMY-NEU- patients, who were minimally impaired. Alternatively, AMY+NEU+ patients were cognitively more impaired than SNAP patients, even when matching on hippocampal volume. SNAP patients present as a distinct MCI group. Their high CSF Aβ42 and florbetapir SUVR levels indicate that subthreshold Aβ42 is unlikely to explain neurodegeneration in this group. The relatively old age, low APOE-ɛ4 prevalence, low conversion rate and predominant hippocampal involvement suggest that primary age-related tauopathy or hippocampal sclerosis may play a role, though the low tau levels do not support the former hypothesis. Moreover, WMH volumes indicate that cerebrovascular disease may contribute to neurodegeneration and cognitive impairment in this group.
Source: Alzheimer s & Dementia
Institution: University of Pennsylvania
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2296780429