REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia
Abstract
Objective: To assess the relationship between the presence of REM sleep behavior disorder (RBD) and the cognitive profile of nondemented patients with Parkinson disease (PD).
Background: Cognitive impairment is an important nonmotor symptom in PD. Waking EEG slowing in nondemented PD has been related to the presence of RBD, a parasomnia affecting brainstem structures and frequently reported in PD. For this reason, RBD may be associated with cognitive impairment in PD.
Methods: Thirty-four patients with PD (18 patients with polysomnographic-confirmed RBD and 16 patients without RBD) and 25 healthy control subjects matched for age and educational level underwent sleep laboratory recordings and a comprehensive neuropsychological assessment.
Results: Patients with PD and concomitant RBD showed significantly poorer performance on standardized tests measuring episodic verbal memory, executive functions, as well as visuospatial and visuoperceptual processing compared to both patients with PD without RBD and control subjects. Patients with PD without RBD had no detectable cognitive impairment compared to controls.
Conclusions: This study shows that cognitive impairment in nondemented patients with Parkinson disease (PD) is closely related to the presence of REM sleep behavior disorder, a sleep disturbance that was not controlled for in previous studies assessing cognitive deficits in PD.
GLOSSARY: BDI-II = Beck-II Depression Inventory; DLB = dementia with Lewy bodies; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; EOG = electro-oculograms; ICSD = International Classification of Sleep Disorders; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PD-NRBD = patients with PD without RBD; PD-RBD = patients with concomitant RBD; RAVLT = Rey Auditory Verbal Learning Test; RBD = REM sleep behavior disorder; UPDRS = Unified Parkinson's Disease Rating Scale.
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Published online: November 5, 2007
Published in print: November 6, 2007
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We read the article by Vendette et al with great interest. [1] We have been prospectively investigating non-demented Parkinson disease (PD) patients with polysomnography (PSG)-confirmed or excluded REM sleep behavior disorder (RBD) and cannot uniformly confirm an association of cognitive impairment with the presence of RBD in PD (e-Table).
In a comprehensive neuropsychological assessment, PD patients with RBD had lower scores in figural fluency, verbal and figural memory tests except for recognition, and had more difficulty with visuo-spatial tasks. PD patients also made more interference errors as in Vendette et al's study, but PD patients with RBD performed better in verbal fluency with fewer perseverations in the Goldenberg test which evaluates concept learning and shifting.
Apraxia, visuo-perceptual, and other cortical deficits were not found in either group but no quantitative measures had been performed. Compared to matched healthy controls (unpublished data), our PD patients with and without RBD showed mild impairment of executive function and memory which can be seen in the early stages of PD. [2] In contrast, PD patients without RBD and healthy controls had similar test results in the study by Vendette et al.
Although statistical significance is lacking, which in some tests might be explained by the smaller number of subjects, and there are differences including other neuropsychological tests and a longer disease duration with more advanced motor impairment in our patients, these results underline the need for a larger prospective study to verify whether RBD is associated with cognitive impairment and predicts later development of dementia as the authors also have suggested. To confirm this second hypothesis, the study should control for cognitive impairment as the latter by itself predicts dementia.
Neuropathological studies could clarify whether degeneration of brainstem nuclei which causes RBD can also manifest with cognitive impairment. [3] Conversely, the association of RBD and cognitive impairment may simply reflect a more widespread neurodegenerative process affecting brainstem and cortex which ultimately leads to dementia.
Table
References
1. Vendette M, Gagnon J-F, Decary A, et al. REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia. Neurology 2007; 69:1843-1849.
2. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 2005; 65:1239-1245.
3. Boeve BF, Silber MH, Saper CB, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007; 130:2770-2788.
Disclosure: The authors report no conflicts of interest.
We thank Dr. Benninger and his colleagues for their comments. Interestingly, in their study, the two between-group comparisons approaching a statistically significant level (Rey auditory verbal learning test and copy of the Rey-Osterrieth complex figure) showed that Parkinson disease (PD) patients with concomitant REM sleep behavior disorder (RBD) performed worse than PD patients without RBD.
These results confirm those obtained in our study using the same cognitive tests assessing verbal memory and visual-spatial constructional abilities. That Benninger et al. did not find differences in other tests may be due to insufficient statistical power. Moreover, the results that Benninger and colleagues claimed was showing a better performance for PD patients with RBD than PD patients without RBD (verbal fluency and Goldenberg test) yielded in fact p values of 0.5. This suggests that any difference is probably due to chance.
In our study, PD patients without RBD performed similarly to the healthy control subjects which is not surprising since approximately one third of patients with PD are cognitively intact. [4] The addition of a control group in Benninger's study would have shed some light on their results.
Although a consensus emerges about a predominant dysexecutive syndrome in PD, some patients present with an amnestic profile or mixed profile. This contributes to the heterogeneity of the results reported in neuropsychological studies of PD, as we have also found in patients with idiopathic RBD. [5] Moreover, comparisons between neuropsychological studies are often difficult. This is due to the heterogeneity of the testing procedures or patient populations; differences in results between neuropsychological studies even on apparently similar patients are not unusual. In PD, the presence of RBD has also been associated with waking EEG slowing, hallucinations, and the non-tremor-predominant form of the disease. [6-8] All of these features are associated with higher risk of developing cognitive impairment in PD, suggesting a common underlying pathophysiological mechanism for these manifestations.
We agree with the need for a larger prospective study to confirm the association between RBD and cognitive impairment in PD. However, we disagree with their suggestion that the groups must be adjusted for baseline impairment, since development of dementia inevitably involves a transition through mild cognitive impairment.
References
4. Janvin C, Aarsland D, Larsen JP, Hugdahl K. Neuropsychological profile of patients with Parkinson's disease without dementia. Dement Geriatr Cogn Disord 2003;15:126-131.
5. Postuma RB, Gagnon JF, Montplaisir J. Cognition in REM sleep behavior disorder – A window into preclinical dementia? Sleep Med; Epub 2007 Sep 13.
6. Gagnon JF, Fantini ML, Bédard MA, et al. Association between waking EEG slowing and REM sleep behavior disorder in PD without dementia. Neurology 2004;62:401-406.
7. Sinforiani E, Zangaglia R, Manni R, et al. REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease. Mov Disord 2006;21:462-466.
8. Kumru H, Santamaria J, Tolosa E, Iranzo A. Relation between subtype of Parkinson's disease and REM sleep behavior disorder. Sleep Med 2007;8:779-783.
Disclosure: J.-F.Gagnon, M. Vendette and R.B. Postuma report no conflicts of interest. J. Montplaisir received personal compensation as consultant (Boehringer Ingelheim, Servier, Shire BioChem), speaker (Boehringer Ingelheim, Shire), and he received financial support for research activities from Sanofi Aventis, GlaxoSmithKline.