Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

Neurobiol Aging. 2017 Oct;58:68-76. doi: 10.1016/j.neurobiolaging.2017.05.019. Epub 2017 Jun 2.

Abstract

Adults with Down syndrome (DS) have a high incidence of Alzheimer's disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the positron emission tomography tracer [11C] Pittsburgh compound B (PiB) across 2 data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex, and anterior ventral striatum. Across the 2 cycles, 14 (27.5%) participants were consistently PiB+, 31 (60.8%) were consistently PiB-, and 6 (11.7%) converted from PiB- at cycle 1 to PiB+ at cycle 2. Increased global amyloid-β was related to decline in verbal episodic memory, visual episodic memory, executive functioning, and fine motor processing speed. Participants who were consistently PiB+ demonstrated worsening of episodic memory, whereas participants who were consistently PiB- evidenced stable or improved performance. Amyloid-β accumulation may be a contributor to or biomarker of declining cognitive functioning in preclinical AD in DS.

Keywords: Alzheimer's disease; Amyloid-β; Dementia; Down syndrome; Mild cognitive impairment; PiB.

MeSH terms

  • Adult
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Cognition / physiology*
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / metabolism*
  • Down Syndrome / metabolism*
  • Down Syndrome / psychology*
  • Executive Function / physiology
  • Female
  • Humans
  • Male
  • Memory, Episodic
  • Middle Aged
  • Phenanthrolines
  • Positron-Emission Tomography
  • Thiazoles
  • Time Factors

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Phenanthrolines
  • Thiazoles