When does cerebral β‐amyloid deposition begin in Lewy body dementia?

Lewy body dementia (LBD) consists of two dementia syndromes associated with Lewy body pathology: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The common pathological basis in the nervous systems supports considerable clinical overlap between them. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD), and psychiatric symptoms are frequently seen in the course of both disorders during the prodromal stage. Although the defining feature of PDD is that dementia develops in the setting of well‐established Parkinson's disease, the presence of parkinsonism is not essential for the clinical diagnosis of DLB. It is accepted that nigrostriatal dopaminergic degeneration is a key pathophysiology in the development of parkinsonism, but the time course of nigral degeneration in LBD remains unclear. In both disorders, cortical Lewy bodies (LBs) and Lewy neurites are often widespread and correlate with the severity of the dementia. The progression pattern of Lewy body pathology in LBD remains unestablished, but the cortical involvement of incidental LBs in individuals without parkinsonism suggests the presymptomatic neuropathological precursor for DLB rather than PDD. Many studies have revealed that cerebral β‐amyloid accumulation is related to the timing of the onset of dementia relative to that of parkinsonism in LBD. Therefore, we focused on the time courses of nigral degeneration and cerebral β‐amyloid accumulation during the disease progression in LBD. Recent neuroimaging and cerebral spinal fluid findings have provided opportunities for understanding the antemortem neuropathological changes, and LBD‐associated findings were also reviewed in this article.