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

Abstract

The present study investigated the characteristics of amnestic mild cognitive impairment (aMCI) in subjects with low brain amyloid-beta (Aβ) burden. Furthermore, the relationships between amyloid-independent cognitive decline and serum lipid profiles, particularly apolipoprotein A1 (APOA1), were evaluated. Cross-sectional and longitudinal follow-up study. University hospital dementia clinic. 28 aMCI and 35 cognitive normal (CN) elderly. The study measures included baseline assessments of the subjects' clinical characteristics, lipid profiles, and magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B (PiB) positron emission tomography scans. Based on PiB retention at baseline, the aMCI subjects were divided into low Aβ (aMCI-) and high Aβ (aMCI+) subgroups. All aMCI subjects were followed up over a 1-year period. 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 Aβ deposition and vascular burden. 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.