Dickson, Dennis W.

AbstractBackgroundFamilies of Dutch‐German‐Russian Mennonite descent with multi‐incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization.MethodsFamily members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy.ResultsOf the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40‐85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology.ConclusionPD associated with a DNAJC13 p.N855S mutation presents as late‐onset, often slowly progressive, usually dopamine‐responsive typical PD. © 2014 International Parkinson and Movement Disorder Society

The pathologic substrate of the clinical syndrome of dementia with Lewy bodies (DLB) remains to be determined. Only a few prospective clinicopathologic studies have been reported. In those reports, most cases of DLB had neocortical or limbic Lewy bodies and Alzheimer-type pathology below threshold for diagnosis of Alzheimer's disease. These results are in accord with recent retrospective clinicopathologic studies of dementia occurring in Parkinson's disease, in which cortical Lewy bodies, rather than concurrent Alzheimer's disease, are increasingly recognized as the pathologic substrate of dementia. Additional clinicopathologic studies are warranted to address the role of other Lewy-related pathology, most notably Lewy neurites, in the cognitive impairment of DLB. (J Geriatr Psychiatry Neurol 2002; 15:000–000).