HEREDITARY FORM OF PARKINSONISM-DEMENTIA

In four generations of a family, 13 members were afflicted with an aut osomal dominant disorder characterized by young age at onset, early we ight loss, and rapidly progressive dopa-responsive parkinsonism, follo wed later by dementia and, in some, by hypotension. Intellectual dysfu nction began with subjective memory loss and objective visuospatial dy sfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cas es showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Oth er findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tang les, or amyloid deposits. Positron emission tomography in 3 patients s howed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltr ansferase activity in the frontal and temporal cortices and hippocampu s and a severe depletion of striatal dopamine with a pattern not typic al of classic Parkinson's disease.