Brain Anomalies in Sleep Behavior Disorder Linked to MCI

Deborah Brauser

June 12, 2018

LOS ANGELES — Abnormalities in cortical and subcortical gray matter may affect cognitive status in patients who have rapid eye movement sleep behavior disorder (RBD), new research suggests.

The study included 52 adult patients with idiopathic RBD (iRBD), including 17 who had mild cognitive impairment (MCI), and 41 healthy controls.

Results showed a significant association between the presence of MCI and subcortical shape contraction in the left putamen and left thalamus. Compared with the healthy controls group, those with both iRBD and MCI had greater abnormal shape contraction in the putamen, thalamus, and left pallidum.

There were no significant differences in outcomes between the control group and those with iRBD and normal cognition.

"We showed that the presence of MCI in these patients is associated with abnormal cortical properties, in terms of thickness, surface area, and volume," lead author Shady Rahayel, Center for Advanced Research in Sleep Medicine at the Hôpital du Sacré-Coeur in Montreal and Department of Psychology at the University of Quebec, Canada, said to attendees at the American Academy of Neurology (AAN) 2018 Annual Meeting.

Shady Rahayel

"We also showed that impairments in all cognitive domains and sensory impairments in these patients are associated with a whole pattern of cortical thinning in several regions," Rahayel told Medscape Medical News afterwards.

Further study findings were published in the May 15 issue of Neurology.

Major Risk Factor

Idiopathic RBD "is a major risk factor" for both Parkinson's disease and dementia with Lewy bodies (DLB), write the investigators. They add that 33% to 50% of these patients present with MCI.

In the current study, "we aimed to investigate the subcortical shape abnormalities underlying cognitive deficits in iRBD patients," the researchers write.

Interestingly, "there have been only a few studies that assessed MRI in these patients," said Rahayel. Most used voxel-based approaches, such as voxel-based morphometry, "and recently we've used surface-based approaches," he added.

The current study population included 52 patients with polysomnography-confirmed iRBD. Of these, 17 also had MCI (71% men; mean age, 67.9 years; mean RBD duration from symptom onset, 12.6 years) and 35 did not have MCI (86% men; mean age, 64.4 years; mean RBD duration, 11.2 years). Mean total scores on the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) were 5.5 and 3.5 for the two groups, respectively.

These groups were compared with 41 individuals who did not have iRBD (61% men; mean age, 63.2 years).

For all 93 participants, 3T MRI was used to produce T1-weighted imaging. In addition to undergoing vertex-based shape analysis of subcortical structures, the study population completed neuropsychological and neurologic assessments.

"Correlation analyses" were also performed, looking into associations between cognitive status and subcortical shape. The three cognitive domains that were focused on were learning and memory, attention and executive functions, and visuospatial abilities. All analyses were adjusted for age, sex, and years of education.

Abnormal Cortical Properties

Results showed that presence of MCI in RBD was associated with abnormal cortical properties, particularly a more contracted shape in the putamen, the pallidum, and the thalamus.

"For the putamen, the thalamus, and the left pallidum, we're talking bilaterally — at least vs the controls. But when we're comparing the RBD patients without MCI to controls, there are no differences," noted Rahayel.

Correlation analyses showed that lower scores on learning and memory, visuospatial ability, and color discrimination tests were associated with a more contracted shape in the right hippocampus only.

"The basal ganglia is known to be impaired in RBD, as demonstrated previously by other studies that have shown abnormal shape contraction or increased blood perfusion or lower dopamine reuptake," noted Rahayel.

"The presence of MCI in this study is associated with abnormalities in subcortical structures, particularly from the basal ganglia. And this is in line with the other findings we just published, where people with RBD and MCI have very extensive cortical thinning," he reported.

"Our results highlight the importance of distinguishing between subgroups of RBD patients based on their cognitive profile in order to develop a better understanding of the neurodegenerative processes in this population."

Why More Vulnerable?

During the postpresentation question-and-answer session, co-moderator Bradley V. Vaughn, MD, professor of sleep medicine and epilepsy at the University of North Carolina School of Medicine, Chapel Hill, asked about possible causes for the outcome differences among the patient groups.

"Do you think the folks with MCI are just more severely ill individuals? Or is there something that is different about their vulnerability so that they're having a contraction in the shape?" asked Vaughn.

"That's a good question. There were no clinical differences: both groups had the same RBD duration, the same UPDRS-III total score, and the same tonic and phasic activity," said Rahayel.

"However, RBD duration is not the ideal way to measure a patient's disease severity. So it could be that these patients were more advanced in terms of severity. We did everything we could to control this aspect but yes, this is a possibility," he added.

When Vaughn asked, "What do you think made them more vulnerable, especially given the right hippocampal atrophy that could impair their visuospatial memory?" Rahayel answered that "it's hard to tell."

He noted that a previous study showed that patients with DLB had a reduction in the right hippocampus that was associated with cognitive dysfunction. "So it could be the case that patients with MCI are already following the same trajectory that may be responsible for DLB," said Rahayel.

"The rationale that might apply to DLB may be the same for people with RBD and MCI. However, what it is exactly that may render them more vulnerable I could not say."

Malignant iRBD Phenotype?

In an accompanying editorial to the journal article, Dario Arnaldi, MD, PhD, and Flavio Nobili, MD, both from the Department of Neuroscience at the University of Genoa, Italy, note that the investigators highlight "the importance of phenotype stratification" in these patients.

"Indeed, iRBD is a heterogeneous condition, with most of the patients developing a neurodegenerative disease after a time ranging from a few to more than 10 years. Such heterogeneity may depend on timing of diagnosis, and iRBD patients with MCI might be at higher risk of short-term conversion, mainly to DLB," they write.

The editorialists add that the current study raises an important question. "Does the presence of MCI identify a malignant iRBD phenotype with a high risk of short-term conversion? Increasing evidence would support this hypothesis."

However, although Rahayel and colleagues suggest that the presence of MCI in these patients is a marker for a severe neurophysiologic phenotype, the researchers did not show longitudinal data. "So whether or not this phenotype has an increased risk of short-term conversion into a definite neurodegenerative disease is still unknown," write Arnaldi and Nobili.

Therefore, larger longitudinal studies are now needed in this patient population, they conclude.

The study was funded by the Canadian Institutes of Health Research, Fonds de Recherche du Québec-Sante, and the W. Garfield Weston Foundation. Rahayel has disclosed no relevant financial relationships. A list of disclosures for the other study authors is in the original article. Arnaldi has disclosed no relevant financial relationships. Nobili has served on the scientific advisory boards of Bayer Schering Pharma and Eli Lilly and has served on the editorial boards of the Journal of Alzheimer's Disease and the Quarterly Journal of Nuclear Medicine and Molecular Imaging.

American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract S17.005. Presented April 23, 2018.

Neurology. 2018;90:909-910, 914-926. Abstract, Editorial

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