COGNITIVE DEFICITS PRECEDE MOTOR DEFICITS IN A SLOWLY PROGRESSING MODEL OF PARKINSONISM IN THE MONKEY

Five adult Macaca fascicularis monkeys were trained to perform tests o f cognitive and motor functioning that included a complex visual patte rn discrimination task, an object retrieval task, a test of task persi stence, and a timed motor task. Once stable baseline performance was a chieved, monkeys were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine (MPTP) at doses of 0.05 to 0.075 mg/kg, 2 to 3 times per wee k for a total of 24 weeks. Animals were assessed weekly for performanc e on the previously learned tasks. All monkeys developed performance d eficits in a predictable pattern with behavioural and cognitive defici ts (i.e. deficits in task persistence and the cognitive component of o bject retrieval) appearing in advance of measurable motor deficits. De ficits in visual pattern discrimination never appeared. These results show that specific cognitive dysfunction pre-dates motor dysfunction i n a chronic, slowly progressing parkinson model in monkeys and support the contention that cognitive deficits in Parkinson's disease may pre cede the motor signs of the disorder and may not be caused by them. (C ) 1995 Academic Press Limited