Dementia with Lewy bodies: Definition, diagnosis, and pathogenic relationship to Alzheimer’s disease

Clinical dementia associated with the appearance of Lewy bodies in the cerebral cortex has been recognized for over 40 years. Until the 1990s, however, cortical Lewy body disease was thought to be a rare cause of dementia. At that time, the advent of sensitive and specific immunohistochemical techniques for highlighting these elusive structures led to the recognition of cortical Lewy body disease as a common substrate for clinical dementia. Current diagnostic criteria recognize dementia with Lewy bodies as a clinicopathological entity. Also recognized is the closely related (and perhaps biologically identical) entity of Parkinson’s disease dementia, which differs from dementia with Lewy bodies only in the temporal sequence of appearance of clinical symptoms. The generic term “Lewy body disease” encompasses both entities. There is frequent and extensive overlap, both clinically and pathologically, between dementia with Lewy bodies and Alzheimer’s disease. The two diseases share several genetic and environmental risk factors that have in common increased inflammatory states associated with increased disease risk. Moreover, pathological and experimental work has implicated the involvement of activated microglia and of microglia-derived interleukin-1 in the pathogenesis of the pathognomonic lesions of both diseases. Such neuroinflammatory processes may be the common link driving progression in both diseases and explaining the frequent overlap between the two diseases.