Aged rhesus monkeys: Cognitive performance categorizations and preclinical drug testing

Area of Science:

• Neuroscience
• Primatology
• Pharmacology

Background:

• Rodent models have limitations in predicting human responses for neuropsychiatric drug development.
• Translational challenges in Alzheimer's disease (AD) research necessitate exploring natural aging and non-human primate models.
• Identifying therapeutic targets requires distinguishing healthy from pathological aging processes.

Purpose of the Study:

• To assess cognitive performance in rhesus monkeys across a spectrum of ages.
• To categorize aged monkeys based on cognitive function (cognitively-unimpaired vs. cognitively-impaired).
• To evaluate the efficacy of a nicotinic acetylcholine receptor (nAChR) agonist in aged, cognitively-impaired non-human primates.

Main Methods:

• Utilized delayed response tasks, including computerized delayed match to sample (DMTS) and manual delayed match to position (DMTP).
• Compared cognitive performance of aged rhesus monkeys to younger subjects.
• Administered encenicline, a nAChR partial agonist, to aged cognitively-impaired monkeys in the DMTP task.

Main Results:

• Older monkeys exhibited a range of cognitive abilities, with some performing comparably to younger subjects and others showing significant impairment.
• Aged monkeys were successfully categorized into "cognitively-unimpaired" and "cognitively-impaired" groups.
• Encenicline demonstrated pro-cognitive effects in aged cognitively-impaired monkeys, validating the model's utility.

Conclusions:

• Rhesus monkeys provide a valuable model for studying age-related cognitive decline and testing potential therapeutics.
• The categorization of aged monkeys allows for targeted investigation of cognitive aging.
• Nicotinic acetylcholine receptor ligands show promise for treating age-related cognitive disorders.