Neurodegenerative Risk in Idiopathic REM

Risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM  (IRBD),  174 patients with a median age at diagnosis of IRBD of 69 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI).Tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA.

Rates of neurological-disease-free-survival according to the time of IRBD diagnosis in the 174 patients from the cohort

Rates of neurological-disease-free-survival according to the time of IRBD diagnosis in the first 44 patients from the cohort (doted line) and the remaining 130 (continuous line)

65 (37.4%) patients were diagnosed with a defined neurodegenerative syndrome, 103 (59.2%) remained disease-free, and 6 (3.4%) were lost to follow-up with the diagnosis of IRBD at their last visit. 

In the brain, all six cases presented variable neuronal loss, gliosis and alpha-synuclein immunoreactive Lewy pathology,  in vulnerable regions such as the olfactory bulb, dorsal motor nucleus vagal nerve, central raphe nucleus, the nuclei that regulate REM sleep muscle atonia (gigantocellular reticular nucleus, pedunculopontine nucleus and coeruleus/subcoeruleus complex), substantia nigra pars compacta, limbic structures (amygdala and anterior cingulate cortex), and nucleus basalis of Meynert. Lewy pathology was also detected in the neocortex.

In the patient with the antemortem diagnosis of PD who did not develop dementia and in the patient with MCI. Lewy pathology was observed in the olfactory bulb, entire brainstem and amygdala, preserving neocortical areas 

 

Confirmation of findings in a much larger cohort would strongly support the notion that IRBD is a manifestation of prodromal PD, DLB or MSA. 

Pathophysiology of the various disorders associated with abnormal synuclein deposition, and could provide the opportunity to test disease-modifying strategies before the onset of motor and cognitive symptoms.