REM Sleep Behavior Disorder and Other Sleep Disturbances in Non-Alzheimer Dementias

Abstract

The study aimed to review recent updates of our understanding of REM sleep behavior disorder (RBD) and other sleep disorders in non-Alzheimer’s disease (AD) dementias. Numerous recent discoveries have provided insight into the role of RBD and sleep in patients with non-AD dementias. Imaging modalities such as DaTscan and cerebral blood flow may be useful for monitoring phenoconversion in idiopathic RBD patients to Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Patients with isolated REM sleep without atonia have non-motor signs of neurodegenerative disease. Colon mucosal biopsies in iRBD patients have shown presence of α-synuclein aggregates. Recent genetic models of RBD and neuroimaging have furthered evidence for the locus subcoeruleus/sublateral dorsal nucleus as the center for the generation and maintenance of REM muscle atonia. Circadian rhythm disturbances likely play a large role in nighttime insomnia, daytime sleepiness, autonomic symptoms, motor variations, and hallucinations in PD and DLB. Early onset stridor in patients with multiple system atrophy (MSA) portends a worse prognosis than late onset stridor, and treatment of stridor is associated with survival. Our ability to predict phenoconversion in idiopathic RBD is improving and will be highly important as “high risk” phenoconverters are identified for enrollment in neuroprotective clinical trials. Treatments of RBD improve but do not fully eliminate DEB; therefore, the risk for sleep-related injury remains a concern even among seemingly well-treated patients. Excessive daytime sleepiness (EDS) secondary to neuropathology, sedating medications, sleep disordered breathing (SDB), restless legs syndrome (RLS), and circadian rhythm alterations are common in the non-AD dementias, leading to significant caregiver burden and worsening of cognition. Addressing primary sleep disorders is the mainstay of treatment for EDS. RLS is a frequent co-morbidity in non-AD dementias. Initial management of RLS includes ensuring serum a ferritin level of >75 μg/L and therapy with gabapentin encarbil (which is less likely to cause augmentation than dopamine agonists). All MSA patients should be evaluated for the presence of nocturnal stridor, which should be treated if present. Therapies targeting the circadian system are often an underutilized therapeutic avenue in the management of sleep, motor, autonomic, and psychiatric symptoms in PD and DLB patients.