Depression Associated With Increased Risk of Neurodegenerative Diseases in Isolated REM Sleep Behavior Disorder

A new study presented at the 2024 SLEEP Annual Meeting, held June 1 to 5, in Houston, Texas, showed that depression was associated with the conversion to neurodegenerative diseases in patients with isolated REM sleep behavior disorder (iRBD). These findings suggest that depressive symptoms in patients with iRBD should be monitored as aggravating cognitive dysfunction and a risk factor for conversion.¹

Among 90 participants included in the study, patients with depression (n = 27) demonstrated a poorer performance in executive function (P = .029, Stroop color test) compared with those in the nondepressed group (n = 63). Additionally, investigators observed lower z-scores in those who had depression in comparison with the nondepressed group in global cognition, attention, memory, and frontal/executive domains.

In the study, lead author In-Young Yoon, MD, PhD, professor in the department of neuropsychiatry at Seoul National University Bundang Hospital, and colleagues analyzed cognitive function and quantified electroencephalography (QEEG) in patients with iRBD based on the presence of depression, and assessed the effect of depression on the conversion to neurodegenerative diseases. Participants were followed up for 9 years, of which 21 had converted to Parkinson disease or dementia. Authors defined phenoconversion when a definitive diagnosis of parkinsonism by neurologists or any form of dementia by geriatric psychiatrists was established according to evident clinical symptoms. The diagnosis of depression was made based on the initial interview or taking antidepressant medication.

Top Clinical Takeaways

Patients with iRBD and depression showed poorer executive function and lower scores in global cognition, attention, memory, and frontal/executive domains.
The study found a significant increase in gamma power in certain brain regions in depressed patients with iRBD, indicating neurological changes associated with depression.
Depression in patients with iRBD significantly increased the risk of conversion to neurodegenerative diseases, suggesting the need for close monitoring and management of depressive symptoms in these patients.

Using QEEG, researchers reported that the relative gamma power in the temporal and parietal region as well as relative high gamma power in the parietal region significantly increased (P = .049; P = 0.032; P = .008) in the patients with depression compared with those without depression. Overall, the conversion to neurodegenerative disorder significantly increased in patients with iRBD who had depression than those with iRBD without depression (P = .013). Notably, investigators observed that depression in patients with iRBD had a 3.319 hazard ratio (P = .011) for the risk of conversion to neurodegenerative diseases.

According to a study published in Sleep Medicine, patients with iRBD and mild cognitive impairment (MCI) have a more impaired cognitive status than those with normal cognition. In the analysis, patients with MCI reported a reduction of cerebral glucose consumption in brain areas critical for cognition, and a more severe deafferentation of the nigrostriatal regions, underscoring the importance of identifying patients with both iRBD and MCI for neuroprotective trials.²

The previously published study included 61 patients with iRBD, 30 of which had MCI (RBD-MCI) and 31 had normal cognition (RBD-NC). Both groups had neuropsychiatric and neuropsychological assessments conducted to evaluate their psychopathological symptoms and neuropsychological functions. In addition, investigators had brain [18F]FDG PET and 123I-FP-CIT-SPECT performed to assess brain glucose metabolism and nigrostriatal dopaminergic function in the convenient subgroups of patients, respectively.

Findings showed that the neuropsychological measures generally confirmed the overall cognitive decline in patients with iRBD-MCI. Authors noted that immediate long-term verbal memory and visuospatial functions, as well as attentional-executive impairment, were evident in the MCI group compared with the NC group. Furthermore, the neuroimaging findings showed a reduction of brain glucose uptake in the bilateral posterior cingulate cortex and more evident nigrostriatal deafferentation in the RBD-MCI group. Notably, investigators reported no differences observed in psychopathological symptoms between the 2 groups.