Research Paper Advance Articles

Age-related cognitive decline in baboons: modeling the prodromal phase of Alzheimer's disease and related dementias

Stephanny Lizarraga1, , Etienne W. Daadi1, , Gourav Roy-Choudhury1, , Marcel M. Daadi1, ,

  • 1 Southwest National Primate Research Center, Texas Biomedical Research Institute, University of Texas Health at San Antonio, San Antonio, TX 78227, USA
  • 2 Research Imaging Institute, Radiology, Cell Systems and Anatomy, University of Texas Health at San Antonio, San Antonio, TX 78227, USA

Received: February 17, 2020       Accepted: May 1, 2020       Published: May 19, 2020      

https://doi.org/10.18632/aging.103272
How to Cite

Copyright © 2020 Lizarraga et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The aging of brain cells and synaptic loss are the major underlying pathophysiological processes contributing to the progressive decline in cognitive functions and Alzheimer’s disease. The difference in cognitive performances observed between adult and aged subjects across species highlights the decline of brain systems with age. The inflection point in age-related cognitive decline is important for our understanding of the pathophysiology of neurodegenerative diseases and for timing therapeutic interventions. Humans and nonhuman primates share many similarities including age-dependent changes in gene expression and decline in neural and immune functions. Given these evolutionary conserved organ systems, complex human-like behavioral and age-dependent changes may be modeled and monitored longitudinally in nonhuman primates. We integrated three clinically relevant outcome measures to investigate the effect of age on cognition, motor function and diurnal activity in aged baboons. We provide evidence of a naturally-occurring age-dependent precipitous decline in movement planning, in learning novel tasks, in simple discrimination and in motivation. These results suggest that baboons aged ~20 years (equivalent to ~60 year old humans) may offer a relevant model for the prodromal phase of Alzheimer’s disease and related dementias to investigate mechanisms involved in the precipitous decline in cognitive functions and to develop early therapeutic interventions

Abbreviations

NHP: Nonhuman primates; CANTAB: Cambridge Automated Neuropsychological Test Battery; ORTBD: the object retrieval task with barrier detour; PFC: prefrontal cortex; CANTAB TT1: Touch training test I; TT2: CANTAB Touch training test II; SD: CANTAB Simple Discrimination; PR: CANTAB Progressive Ratio; NPCRA: Nonparametric circadian rhythm analysis; MoL: method of loci.