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A Role for Extranigral Factors?

John C. Morris, MD; Mark Drazner; Keith Fulling, MD; Elizabeth A. Grant, PhD; James Goldring, PhD, MD

Arch Neurol. 1989;46(6):651-657.

Abstract
• 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.

Author Affiliations
From the Departments of Neurology and Neurosurgery (Neurology) (Drs Morris and Goldring and Mr Drazner), Pathology (Neuropathology) (Dr Fulling), and Biostatistics (Dr Grant) and the Alzheimer's Disease Research Center (Drs Morris, Fulling, and Grant), Washington University School of Medicine, St Louis, Mo. Dr Fulling is now with St John's Mercy Medical Center, St Louis, Mo.

Footnotes
Accepted for publication November 17, 1988.

A preliminary version of this paper was presented at the Fourth Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated With Aging, Zurich, Switzerland, January 17, 1987.

Reprint requests to Department of Neurology, Box 8111, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110 (Dr Morris).

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