Dementia in idiopathic Parkinson's disease. A neuropathological study of 32 cases

Abstract

Neuronal loss was estimated semiquantitatively in the substantia nigra (SN) and locus coeruleus (LC), and by cell counts in the nucleus basalis of Meynert (NBM), in 32 patients with idiopathic Parkinson's disease (14 non-demented and 18 demented). The number of senile plaques (SP) and neurofibrillary tangles (NFT) was rated in four cortical areas. Neuronal loss in the SN seemed in dependent of mental impairment, while severe lesions of the LC were more frequent in demented patients. In the NBM, neuronal loss and Lewy bodies were observed in most cases (95%) and were associated with significant reductions of choline acetyltransferase (CAT) activity both in the NBM and the cortex (measurements available for 13 cases). This confirms that the cholinergic innominato-cortical pathway is damaged in Parkinson's disease and that the lesion is severer in subjects with dementia. SP and NFT were present in the cortex in 75% of the cases and significantly more numerous in demented patients. However, in 37% of the cases (six cases with dementia), the score for cortical changes was low and could be related to age. Cortical SP and NFT were not correlated to the degree of cell loss in LC and NBM, or to CAT activity in the cortex or NBM. Damage to coeruleo-cortical, innominato-cortical and intra-cortical neurones could each play a role in the appearance of dementia in Parkinsonism. The lesions in the different neuronal systems do not seem to evolve in parallel, but may be additive or potentiate one another in terms of functional expression. Also, the variety in extent and degree of lesions encountered in Parkinson's disease may offer a pathological substrate for the wide variety of mental symptoms described in this illness.