Dementia with Lewy bodies: Implications for clinical trials

The neurobehavioral and pathologic features of Parkinson disease dementia (PDD) are virtually identical to those of dementia with Lewy bodies (DLB), suggesting that they represent different phenotypes of the same underlying disease. Both are characterized clinically by a "frontal-subcortical" dementia, fluctuating confusion, and, often, psychotic symptoms. Pathologically they are characterized by disseminated Lewy bodies and multiple transmitter deficits. These dementias with Lewy bodies constitute the second leading cause of dementia after Alzheimer disease (AD), and are thus an important treatment target. No drug has yet been approved for these indications, but treatment options are emerging. This paper addresses the conduct of clinical trials for this indication, including definition of target populations, screening metrics, outcome measures, and clinical trial designs. As the pathophysiology of these cognitive and behavioral changes becomes better understood, symptomatic as well as disease-modifying therapy may become possible, requiring an inclusive and consistent approach to clinical trials in this area.