Cognitive deficits precede motor deficits in a slowly progressing model of parkinsonism in the monkey

Abstract

Five adult Macaca fascicularis monkeys were trained to perform tests of cognitive and motor functioning that included a complex visual pattern discrimination task, an object retrieval task, a test of task persistence, and a timed motor task. Once stable baseline performance was achieved, monkeys were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at doses of 0.05 to 0.075 mg/kg, 2 to 3 times per week for a total of 24 weeks. Animals were assessed weekly for performance on the previously learned tasks. All monkeys developed performance deficits in a predictable pattern with behavioural and cognitive deficits (i.e. deficits in task persistence and the cognitive component of object retrieval) appearing in advance of measurable motor deficits. Deficits in visual pattern discrimination never appeared. These results show that specific cognitive dysfunction pre-dates motor dysfunction in a chronic, slowly progressing parkinson model in monkeys and support the contention that cognitive deficits in Parkinson's disease may precede the motor signs of the disorder and may not be caused by them.