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

Am J Geriatr Psychiatry. 2016 Feb;24(2):144-53. doi: 10.1016/j.jagp.2015.06.004. Epub 2015 Jun 26.

Abstract

Objectives: 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.

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 (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.

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 Aβ 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.

Keywords: Alzheimer disease; Amyloid PET; MRI; apolipoprotein; mild cognitive impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Amnesia / blood*
  • Amyloid / metabolism*
  • Aniline Compounds / administration & dosage
  • Apolipoprotein A-I / blood*
  • Atrophy
  • Brain / pathology*
  • Brain Mapping
  • Cognitive Dysfunction / blood*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Linear Models
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Radiopharmaceuticals / administration & dosage
  • Thiazoles / administration & dosage

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • APOA1 protein, human
  • Amyloid
  • Aniline Compounds
  • Apolipoprotein A-I
  • Radiopharmaceuticals
  • Thiazoles