Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study

Alzheimers Dement. 2016 Jul;12(7):805-14. doi: 10.1016/j.jalz.2015.12.009. Epub 2016 Jan 21.


Introduction: The present study investigated the relationship between beta-amyloid (Aβ) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD).

Methods: One eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Aβ burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed.

Results: Higher Aβ was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Aβ was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) ε4 status moderated the relationship between Aβ and cognitive trajectories (P values <.01).

Discussion: In individuals at risk for AD, greater Aβ in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline.

Keywords: APOE; Alzheimer's disease; Amyloid imaging; Cognition; Mild cognitive impairment; Preclinical Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Brain / metabolism
  • Cognitive Dysfunction / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Neuropsychological Tests / statistics & numerical data
  • Positron-Emission Tomography / methods
  • Prodromal Symptoms
  • Registries
  • Wisconsin


  • Amyloid beta-Peptides