Choline acetytransferase activity and striatal dopamine receptors in Parkinson's disease in relation to cognitive...

Brain tissue from 44 patients with Parkinson's disease (PD) and 36 age-matched controls was examined for choline acetyltransferase (ChAT) activity, and for densities of D1 and D2 dopamine receptors. Brain samples were examined for Alzheimer' disease (AD) type changes and for Lewy bodies (LBs), and for apolipoprotein E genotype. Patients were evaluated for the stage of cognitive impairment using Reisberg's global deterioration scale. ChAT activity in PD was reduced in all brain areas examined, being 51% of the control mean in the hippocampus (P<0.001), 57% in the prefrontal cortex (P< 0.001) and 64% in the temporal cortex (P<0.001). The number of LBs had a significant negative correlation with ChAT activity in both prefrontal (r=-0.33, P<0.05) and temporal cortex (r=-0.32, P<0.05). The reduction in ChAT activity in the prefrontal cortex had a significant negative correlation (r=-0.38, P=0.012) with the extent of cognitive impairment. When the CERAD class 'C' was excluded, cognitive impairment correlated significantly with both prefrontal ChAT activity (r=-0.52, P=0.0051) and the density of D1 dopamine receptors in the caudate nucleus (r=-0.40, P=0.037). The number of D1 and D2 dopamine receptors was reduced in both caudate nucleus and putamen in PD patients without neuroleptics as compared to controls. An increased D2 receptor number was found in the caudate nucleus and putamen in PD patients treated with neuroleptics. The present study showed that cognitive decline in PD is associated with reduced ChAT activity in the prefrontal cortex and the D1 dopamine receptor number in the caudate nucleus, even in the absence of AD-type pathology.