Similarities and Differences in Cognitive Deficits and Responsiveness to L-Dopa between Aged and MPTP-Treated Cynomolgus Monkeys Tested on the Same Tasks

Abstract

Cognitive and motor declines are two major geriatric problems often coexisting in older adults. Also, mild cognitive impairment (MCI) is frequently observed in patients with Parkinson’s disease (PD) in addition to motor dysfunction. Amelioration of cognitive deficits, either in patients with PD or in senescence, has proven problematic in the clinic; due, in part, to a poor understanding of the mechanism underlying PD-MCI and age-associated cognitive declines. Thus, a better characterization of similarities and differences between age-associated and disease-related cognitive impairments should help better design therapeutic strategies tailored to restore cognitive functions in either the elderly or PD patients. In the present study, eighteen cynomolgus monkeys were trained and tested on a delayed matching-toposition (DMTP) and delayed matching-to-sample (DMTS) task, including 6 middle-aged, 6 aged, and 6 MPTP-treated animals. After a 3-month break, cognitive testing was resumed in all animals both before and after a 4-day treatment regimen with oral L-dopa. Here, we are reporting that 1) delay-dependent declines in percentage accuracy were seen on both tasks in normal (MPTP naive) animals while only seen on the DMTP task in MPTP-treated animals, 2) animals with MPTP-induced dopamine deficiency had a greater difficulty learning and performing on the DMTS task compared to normal animals, 3) L-dopa treatment did not improve cognitive performance on either task in any animals, but rather led to a worsening in performance on the DMTP task in normal middle-aged and MPTP-treated animals, and 4) cognitive declines correlated with age only on the DMTS but not on the DMPT task. Our results suggest that cognitive impairments seen in animals with MPTP-induced dopamine deficiency differ from those seen in aged animals.