To examine the natural history and pathogenesis of parkinsonism in Alzheimer's disease, 44 subjects with clearly established senile dementia of the Alzheimer type were studied during a 66-month period. Sixteen subjects (36%) developed idiopathic parkinsonism, and 12 subjects (27%) developed drug-induced parkinsonism; the chief clinical features of both types were bradykinesia and rigidity, but not resting tremor. The presence of parkinsonism was associated with global (rather than selective) cognitive impairment, as determined by psychometric testing, and with more rapid progression to advanced stages of dementia. The pathological correlates of clinical parkinsonism were heterogeneous in 10 subjects with Alzheimer's disease who were examined post mortem. Coexistent Parkinson's disease was observed in five cases and nonspecific nigral degenerative lesions were present in another three; however, two cases had neither histological changes nor reduced neuronal densities in the substantia nigra. These two cases suggested that extranigral lesions, possibly involving mesocortical dopaminergic pathways, may contribute to the development of parkinsonism in subjects with Alzheimer's disease.

Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was the priMarchy dementing illness. Seventeen of the 26 SDAT subjects had been diagnosed when only mildly demented. Two control subjects were examined neuropathologically; AD was absent in both. We conclude that research clinical diagnostic criteria for SDAT, even in its mild stage, are valid.

An 82-year-old cognitively healthy man was assessed longitudinally until very mild senile dementia of the Alzheimer type was diagnosed by clinical research criteria and documented by psychometric testing at age 85 years. Four months after diagnosis, Alzheimer's disease was confirmed neuropathologically. The diagnostic difficulties involved in distinguishing early senile dementia of the Alzheimer type-Alzheimer's disease from normal aging are examined and clinical and pathologic features useful for their discrimination are discussed.