Figure 9.

Schematic representation of the hypothesized progression in functioning with increasing age and disease severity in evolving Lewy body disease (LBD) in the Parkinson's disease (PD)- and dementia with Lewy bodies (DLB)-predominant phenotypes, and the potential effect of therapy. The onset of REM sleep behavior disorder (RBD) typically begins many years prior to the onset of cognitive decline and a diagnosis of mild cognitive impairment (MCI), and/or many years prior to the onset of motor decline and detectable mild parkinsonian signs (MPS). Progression typically continues over subsequent years to either PD or DLB, and ultimately on to death. This evolution of progression in the current era of primarily symptomatic treatments, with no agent convincingly showing altered progression in the underlying disease process of LBD, is depicted by the red line marked “a”.

One could envision at least four potential effects of a synucleinopathy-active therapy (labeled “Tx” and instituted along the time course as shown by the orange arrow) in patients with appropriately identified “idiopathic” RBD. The agent could slow down the rate of progression (as shown by the green line marked “b”), or delay the onset of cognitive and/or motor decline (as shown by the green line marked “c”), or prevent progression to cognitive and motor decline altogether (as shown by the green line marked “d”). Or, perhaps a synucleinopathy-active therapy could delay the onset of symptoms and slow down the rate of progression (as shown by the green line marked “e”).