Amyloid-Independent Amnestic Mild Cognitive Impairment and Serum Apolipoprotein A1 Levels

Abstract

Objectives: The present study investigated the characteristics of amnestic mild cognitive impairment (aMCI) in subjects with low brain amyloid-beta (Ab) burden. Furthermore, the relationships between amyloid-independent cognitive decline and serum lipid profiles, particularly apolipoprotein A1 (APOA1), were evaluated. Design: Cross-sectional and longitudinal follow-up study. Setting: University hospital dementia clinic. Participants: 28 aMCI and 35 cognitive normal (CN) elderly. Measurements: The study measures included baseline assessments of the subjects' clinical characteristics, lipid profiles, and magnetic resonance imaging and C-11-labelled Pittsburgh Compound B (PiB) positron emission tomography scans. Based on PiB retention at baseline, the aMCI subjects were divided into low A beta (aMCI-) and high A beta (aMCI+) subgroups. All aMCI subjects were followed up over a 1-year period. Results: The aMCI- group had a longer duration of illness than did the aMCI \ group. None of the aMCI subjects were diagnosed with Alzheimer disease (AD) dementia during the 1-year follow-up period, whereas 26.7% of aMCI+ subjects developed AD dementia. The aMCI- group also exhibited lower serum APOA1 levels compared with both the aMCI+ and CN groups. Additionally, lower serum APOA1 levels were associated with cognitive decline and brain atrophy independent of A beta deposition and vascular burden. Conclusions: Patients with aMCI- likely exhibit different clinical and pathophysiological characteristics than patients with aMCI+. Additionally, APOA1 may be an important contributor underlying amyloid-independent neurodegeneration.