Acute and Long-Term Administration of Anticholinergics in Parkinson's Disease: Specific Effects on the Subcortico-Frontal Syndrome

Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood. Most studies have focused on the well-known nigro-striatal dopaminergic degenerations of PD, but a more satisfying understanding of the SCFS has come from the study of the cholinergic systems. We present here two new experiments carried out with long-term and acute anticholinergic treatments in PD. In the first experiment, the effects of a 2-week treatment with trihexyphenidyl were compared to those observed under placebo on a neuropsychological battery. Results showed that anticholinergic-induced deficits in PD were exclusively concerned with executive functions. In the second experiment, the effects of an acute subclinical dose of scopolamine were compared between normal controls and PD patients who were devoid of cognitive deficit on a subset of executive tasks. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions—such as Alzheimer's disease—cholinergic blockade in PD exacerbates specifically the SCFS. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.