Cognitive Impairment
After the first years, researchers have turned their interest toward other motor and nonmotor symptoms. Among those, the cognitive disturbances reported in PD patients have retained their interest. To specifically address those cognitive impairments, Schneider and colleagues developed an intoxication paradigm in the macaque monkey leading to cognitive impairment before the motor symptom take place (Schneider 1990; Schneider and Kovelowski 1990; Roeltgen and Schneider 1991, 1994; Schneider et al. 1992; Schneider and Roeltgen 1993). MPTP is administered at low doses, several times per week for several months. MPTP administration continues until cognitive deficits appear in the absence of parkinsonian motor impairment. Animals are considered “cognitively impaired” if they show at least a 15% decrease in cognitive task performance (Schneider and Kovelowski 1990; Schneider and Roeltgen 1993; Decamp and Schneider 2004, 2006; Decamp et al. 2004). Measurement of cognitive performance is by a computer-controlled touch-screen battery of tests that have been validated in this model. The so-called “chronic low-dose” MPTP-treated macaque monkeys develop impairments in the performance of spatial delayed responses, delayed matching-to-sample, delayed alternation, object retrieval and discrimination reversal tasks, as well as a variety of specific impairments of attentional and executive functions (Schneider and Kovelowski 1990; Schneider and Roeltgen 1993; Decamp and Schneider 2004, 2006; Decamp et al. 2004). This model has particular relevance to the evaluation and development of cognition-enhancing drugs to treat the neuropsychological aspects of PD, in which fronto-striatal dysfunction has been implicated.
ความบกพร่องทางสติปัญญาAfter the first years, researchers have turned their interest toward other motor and nonmotor symptoms. Among those, the cognitive disturbances reported in PD patients have retained their interest. To specifically address those cognitive impairments, Schneider and colleagues developed an intoxication paradigm in the macaque monkey leading to cognitive impairment before the motor symptom take place (Schneider 1990; Schneider and Kovelowski 1990; Roeltgen and Schneider 1991, 1994; Schneider et al. 1992; Schneider and Roeltgen 1993). MPTP is administered at low doses, several times per week for several months. MPTP administration continues until cognitive deficits appear in the absence of parkinsonian motor impairment. Animals are considered “cognitively impaired” if they show at least a 15% decrease in cognitive task performance (Schneider and Kovelowski 1990; Schneider and Roeltgen 1993; Decamp and Schneider 2004, 2006; Decamp et al. 2004). Measurement of cognitive performance is by a computer-controlled touch-screen battery of tests that have been validated in this model. The so-called “chronic low-dose” MPTP-treated macaque monkeys develop impairments in the performance of spatial delayed responses, delayed matching-to-sample, delayed alternation, object retrieval and discrimination reversal tasks, as well as a variety of specific impairments of attentional and executive functions (Schneider and Kovelowski 1990; Schneider and Roeltgen 1993; Decamp and Schneider 2004, 2006; Decamp et al. 2004). This model has particular relevance to the evaluation and development of cognition-enhancing drugs to treat the neuropsychological aspects of PD, in which fronto-striatal dysfunction has been implicated.
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