The Contribution of Non-Dopaminergic Pathology to Cognitive, Motor and Affective Disability in Parkinson’s Disease

Abstract

Cognitive deficits in Parkinson’s disease (PD) are now well recognised although the pathophysiological basis of the deficits remains uncertain (reviewed by Brown and Marsden, 1988; Sagar and Sullivan, 1988). The cognitive deficits occur particularly on “executive” tasks, which are known to be sensitive to frontal lobe dysfunction raising the possibility that a frontal lobe disorder is the basis of the majority of the cognitive impairment in the disease. The pathogenesis of the cognitive deficits remains uncertain but most investigators have concentrated on the role of the “complex” loop between the caudate nucleus and prefrontal cortex (De Long et al., 1984). A deficiency of caudate dopamine is regarded as the principal cause of dysfunction within this loop. Another contributing factor may be dopamine deficiency in the ventral tegmental area leading to dysfunction in the mesocortical projections to the frontal cortex (Javoy-Agid and Agid, 1980; Sagar, 1985).