Acta Neuropathol (Berl) (1984) 64: 43- 52 Acta Neuropathologica 9Springer-Verlag1984 Dementia in Idiopathic Parkinson's Disease* A Neuropathological Study of 32 Cases P. Gaspar and F. Gray Laboratoire de Neuropathologie Charles Foix, H6pital de la Salp~tri+re, 47, Bd. de l'H6pital, F-75651 Paris C6dex 13, France Summary. Neuronal loss was estimated semiquan- titatively in the substantia nigra (SN) and locus coe- ruleus (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 dement- ed). The number of senile plaques (SP) and neurofibril- lary 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 neu- rones 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. Key words: Parkinson's disease - Nucleus basalis of Meynert - Dementia Offprint requests to: P. Gaspar * This work is dedicated to the memory ofPr. R. Escourolle. As the head of the laboratoire Charles Foix, he had followed this work with great interest Introduction At the present time, most authors tend to agree that mental disturbance, and particularly organic dementia, is more frequent in patients with Parkinson's disease than in age-matched control populations (Martilla and Rinne 1976; Lieberman et al. 1979; Mayeux et al. 1981 ; Mindham et al. 1982), although estimates of the frequency of mental impairment range from 14% to 40% (for review see Mindham et al. 1982). These differences may be attributed to various factors: whether the study is prospective or retrospective, the choice of the control population, the type of mental symptom analysed (depression, impairment of cog- nitive or motor skills, memory impairment or distur- bance of instrumental functions). How the mental symptoms observed in parkin- sonism relate to pathological and biochemical alter- ations is an open question. A number of recent studies have dealt with this issue and have suggested that abnormalities in several neuronal systems might be implied. Thus, Hakim and Mathieson (1979) and Boller et al. (1980) have shown that cortical changes consistent with Alzheimer's disease were frequently found in parkinsonian patients and that a relationship with dementia was present (Boller et al. 1980; Jellinger and Riederer 1984). In addition to these neuropathological studies, biochemical analyses have shown reduced levels of several neurotransmitters in the cortex: dopamine, noradrenalin, serotonin (Scatton et al. 1983), as well as choline acetyltransferase (CAT) activity (Ruberg et al. 1982, 1983; Dubois et al. 1983), used as a marker for cholinergic neurones. However, loss of these amines does not reflect damage to neurones within the cortex but indicates lesions of afferent fibres and terminals which arise from subcortical nuclei, the substantia nigra and ventral tegmental area (dopamine), and locus coeruleus (noradrenalin); the dorsal raphe nucleus