Figure 5.

Schematic of brainstem nuclei and connections pertinent to REM sleep, movement, and cognition. As per the Braak staging scheme, the temporal sequence of α-synuclein pathology begins mainly in the medulla and then ascends to the cortex (6 stages). In stage 1 (not shown), the dorsal IX/X motor nucleus, intermediate reticular zone, and olfactory bulb is affected, with presumably coexisting degenerative changes in these structures. In stage 2, there is progression in the structures involved in stage 1, plus the caudal raphe nuclei, MCRF, Peri-LC structures, and possibly SLD. RBD may evolve when sufficient degenerative changes have occurred in the SLD, peri-LC structures, and MCRF (denoted by red Xs within nuclei). In stage 3, there is progression in the structures involved in stage 2, plus the PPN, SN, and NBM (denoted by red Xs within nuclei). When sufficient degeneration occurs in the SN, then parkinsonism becomes manifest. When sufficient degeneration occurs in the NBM, then cognitive changes may become manifest. Additional α-synuclein pathology and neurodegeneration evolves in limbic and neocortical structures over stages 4-6 (not shown). This temporal sequence of pathology could explain why RBD precedes parkinsonism and dementia in many patients with Lewy body pathology.

Abbreviations: AHC=anterior horn cell, LC=locus coeruleus, LDTN=laterodorsal tegmental nucleus, LPT=lateral pontine tegmentum, MCRF=magnocellular reticular formation, NBM=nucleus basalis of Meynert, PC=pre-coeruleus, PPN=pedunculopontine nucleus, SLD=sublaterodorsal nucleus, SN=substantia nigra, vlPAG=ventrolateral part of the periaqueductal grey matter