PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of neurologyNeurologyAmerican Academy of Neurology
 
Neurology. Dec 11, 2012; 79(24): 2302–2306.
PMCID: PMC3578380
Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder
Thien Thanh Dang-Vu, MD, PhD,corresponding author
Scientific Advisory Boards:
  • NONE
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • NONE
Editorial Boards:
  • NONE
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • NONE
Research Support, Commercial Entities:
  • NONE
Research Support, Government Entities:
  • Funded by the Canadian Institutes of Health Research, the Belgian Fonds National de la Recherche Scientifique, and Wallonie-Bruxelles International.
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • Funded by the Fonds Léon Frédéricq, the Belgian College of Neuropsychopharmacology and Biological Psychiatry, the European Sleep Research Society, the Belgian American Educational Foundation, the Belgian Neurological Society, and the Horlait-Dapsens Medical Foundation.
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
Jean-François Gagnon, PhD,
Scientific Advisory Boards:
  • NONE
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • Movement Disorders Society, Travel/Speaker honoria for annual congress, Toronto, Canada, 2011; RBD Study Group, Travel/Speaker honoria for annual symposium, Otsu, Japan, 2011.
Editorial Boards:
  • NONE
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • NONE
Research Support, Commercial Entities:
  • NONE
Research Support, Government Entities:
  • Dr. Gagnon receives research support from the Canadian Institutes of Health Research [MOP-84482 (PI, 2007-2012), MOP-62955 (Co-PI, 2008-2013), MOP-191058 (Co-Inv, 2009-2014) and MOP-93802 (Co-PI, 2010-2015)] and Fonds de Recherche du Québec - Santé [11834 (PI, 2007-2010)].
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • NONE
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
Mélanie Vendette, MSc,
Scientific Advisory Boards:
  • NONE
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • NONE
Editorial Boards:
  • NONE
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • NONE
Research Support, Commercial Entities:
  • NONE
Research Support, Government Entities:
  • NONE
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • NONE
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
Jean-Paul Soucy, MD, MSc,
Scientific Advisory Boards:
  • NONE
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • NONE
Editorial Boards:
  • Member, Editorial Board, Advances in Alzheimer's Disease,2012 -
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • I practice Nuclear Medicine at both the Montreal, University Medical Centre and Montreal Neurological, Hospital, and I report both SPECT rCBF studies and PET FDG, brain studies as a practitioner.
Research Support, Commercial Entities:
  • NONE
Research Support, Government Entities:
  • 24. Beta-cell imaging with 18F-labeled, glibenclamide-glucose conjugates by positron emission, tomography. CIHR 97970; SCHIRRMACHER, R, SOUCY, JP;, $79,462/année x 3 ans (2010), 25. Sleep and mild cognitive impairment. CIHR MOP-102631. MONTPLAISIR J, GAGNON JF, GOSSELIN N, MONCHY O, SOUCY JP. $169,465/année X 5 ans (2010)26. Anatomobehavioral validation of the [18F]fluoroethoxybenzovesamicol, as a PET radiotracer for the diagnosis of Alzheimer's disease. CIHR. Co-PI: BÉDARD, MA, SOUCY JP, ROSA P. Collaborators : DESCARRIES L, MESHAWAR N. $50 000.00 X 1 an (2010), 27. Development of an automated blood counter for quantitative molecular imaging applications. Després, Philippe (IP). CO-APPLICANT(S): Soucy, Jean-Paul; Rosa, Neto, Pedro; Hamel, Louis-André. Projets de recherche, concertée sur la santé (PRCS), programme conjoint CRSNG et, IRSC. Projet # 1004158. 2010: $73000, 2011: $110300, 2012: $61800, 28. In vivo quantification of glutamatergic abnormalities, in patients with Alzheimer's disease. Rosa-Neto, Pedro, (IP); Co-applicants: Gauthier, Serge; Soucy, Jean-Paul. IRSC, demande # 245908, comité BCA. $196,180/année X 4, ans (2011-2014), 29. The neuro-circuitry of terror: High resolution SPECT, imaging of REM sleep in PTSD and Nightmare Disorder. IPs: Nielsen, Torre; Soucy, Jean-Paul. Co-applicant: Montplaisir, Jacques. CIHR MOP-115125. $135 550/année X 5, ans (2011-2015) 30. Anomia in Alzheimer's disease : Untangling semantic, components and delivering therapy with rTMS. Chertkow, Howard, Soucy Jean-Paul, Thiel Alexander. CIHR 259005. $153 303.00/year, 2012-2015, 31. Obstructive sleep apnea and mild cognitive impairment. N Gosselin , J. Y. Montplaisir, L. De Beaumont, J. Gagnon, S. Gauthier, J. P. Soucy. CIHR 272199. $157,816/année, 2012-2016
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • NONE
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
Ronald B. Postuma, MD,
Scientific Advisory Boards:
  • (1) Teva Neurosciences, Panel Member, 2008
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • (1) Allergan, 2011; (2) Teva Neurosciences, 2011, Novartis 2012
Editorial Boards:
  • (1) Editorial Board, Movement Disorders Journal; (2) Editorial Board, Journal of Caffeine Research
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • NONE
Research Support, Commercial Entities:
  • NONE
Research Support, Government Entities:
  • (1) Operating Grant - Canadian Institute of Health Research/Parkinson Society of Canada, grant number 201317, Principal Investigator (10/2009 - 10/2011); (2) Operating Grant - Canadian Institute of Health Research, grant number 192205, co-Principal Investigator (07/2009 - 06/2010); 3. Operating Grant - Canadian Institute of Health Research, grant number 166206 Co-investigator (07/2007 to 06/2012); (4) An Emerging Team in Mobility in Aging, Operating Grant - Canadian Institute of Health Research, Co-investigator (01/2009 - 12/1013); (4) Fonds de Recherche de la Sante Quebec, grant number 9965, Principal Investigator (2006-2009)
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • (1) Operating Grant - Weston Foundation, Prinicipal Investigator (01/2009 - 01/2011); (2) Operating grant - Drummond Foundation, Principal Investigator (01/2008 - 04/2009)
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
and Jacques Montplaisir, MD, PhDcorresponding author
Scientific Advisory Boards:
  • Servier, advisor, 2009; Merck, advisor, 2009-2010 Sanofi-Aventis, 2009-2011; Valeant Pharmaceutical,2011-2012; GSK Pharma 2011-2012
Gifts:
  • NONE
Funding for Travel or Speaker Honoraria:
  • Valeant Pharmaceutical, Speaker 2010 and 2011; Otsuka Pharmaceutical, Speaker, Japan 2011
Editorial Boards:
  • (1) Associate editor: Sleep Medicine; (2) Associate editor: Sleep Medicine Reviews
Patents:
  • NONE
Publishing Royalties:
  • NONE
Employment, Commercial Entity:
  • NONE
Consultancies:
  • NONE
Speakers' Bureaus:
  • NONE
Other Activities:
  • NONE
Clinical Procedures or Imaging Studies:
  • NONE
Research Support, Commercial Entities:
  • Merck 2010 - Unrelated to the study, GlaxoSmithKline 2011 - Unrelated to the study
Research Support, Government Entities:
  • PI: CIHR - MOP-62955 - 2008-2013; PI: CIHR - MOP-106692 - 2011-2015, PI: CIHR- MOP- 102631 - 2010-2015, Co-I: CIHR - MOP- 97825 - 2011-2016; Co-I: CIHR - MOP-115125 - 2012-2017; Co-PI: CIHR - MOP 173519 - 2007-2012, Co-I: CIHR - MOP 64221 - 2008-2012
Research Support, Academic Entities:
  • NONE
Research Support, Foundations and Societies:
  • NONE
Stock/Stock Options/Board of Directors Compensation:
  • NONE
License Fee Payments, Technology or Inventions:
  • NONE
Royalty Payments, Technology or Inventions:
  • NONE
Stock/Stock Options, Research Sponsor:
  • NONE
Stock/Stock Options, Medical Equipment & Materials:
  • NONE
Legal Proceedings:
  • NONE
From the Center for Advanced Research in Sleep Medicine (T.T.D.-V., J.-F.G., M.V., R.B.P., J.M.), Hôpital du Sacré-Cœur de Montréal; Department of Exercise Science and Center for Studies in Behavioral Neurobiology (T.T.D.-V.), Concordia University, Montréal, Canada; Cyclotron Research Centre (T.T.D.-V.), University of Liege; Department of Neurology (T.T.D.-V.), Centre Hospitalier Universitaire de Liège, Belgium; Department of Psychology (J.-F.G.), Université du Québec à Montréal; Montreal Neurological Institute (P.S.), McGill University, Montréal; Department of Nuclear Medicine (J.P.-S.), Centre Hospitalier de l’Université de Montréal; Department of Neurology (R.B.P.), Montreal General Hospital; and Department of Psychiatry (J.M.), University of Montreal, Canada.
corresponding authorCorresponding author.
Correspondence & reprint requests to Dr. Dang-Vu, tt.dangvu/at/concordia.ca or Dr. Montplaisir, jy.montplaisir/at/umontreal.ca
Study funding: Supported by the Canadian Institutes of Health Research and by the Fonds de recherche du Québec–Santé.
Go to Neurology.org for full disclosures. Disclosures deemed relevant by the authors, if any, are provided at the end of this article.
Received April 25, 2012; Accepted July 27, 2012.
Objectives:
Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with 99mTc–ethylene cysteinate dimer (ECD).
Methods:
Twenty patients with IRBD were scanned at baseline during wakefulness using 99mTc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process.
Results:
Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients.
Conclusions:
99mTc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.
Idiopathic REM sleep behavior disorder (IRBD)—a condition characterized by dream-enactment behaviors—is frequently associated with the subsequent development of other presumed synucleinopathies: Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).1 The physiopathology underlying this association remains unclear.
Some studies have attempted to identify biomarkers predictive of an evolution toward PD, DLB, or MSA. For instance, patients with IRBD who would evolve had worse baseline scores for olfaction and color vision than those who would remain stable.2 In addition, transcranial ultrasound of substantia nigra and dopaminergic imaging show promise as predictors of evolution.3
In this study, we aimed to characterize the brain perfusion patterns at baseline that predicted future evolution from isolated IRBD to other neurodegenerative diseases, using SPECT with 99mTc–ethylene cysteinate dimer (ECD). Because previous 99mTc-ECD SPECT studies in patients with IRBD highlighted perfusion changes in the pons, striatum, and hippocampus, as well as neocortical areas (frontal, temporoparietal),4 we hypothesized that patterns predictive of the conversion would be part of these structures.
Subjects.
Patients had an interview with a sleep specialist and a polysomnographic recording at the Sacre-Coeur Hospital to confirm the diagnosis of REM sleep behavior disorder (RBD). All patients discontinued psychotropic medications for the study. Their neurologic evaluation included a motor assessment with the Unified Parkinson Disease Rating Scale (UPDRS)-III, color vision discrimination by the Farnsworth-Munsell (FM)-100 test, and olfactory identification by the University of Pennsylvania Smell Identification Test 12 items (UPSIT-12). Exclusion criteria were psychiatric condition or dementia according to DSM-IV-TR and neuropsychological assessment, Mini-Mental State Examination score <26, and other sleep and neurologic disorders. Twenty patients with IRBD met the criteria for inclusion; 12 of them were also part of a previous study.4 Neurologic, neuropsychological, and SPECT assessments were performed during the same week. Although all IRBD patients were free of PD, DLB, and MSA at the time of scanning (baseline), 13 of them had mild cognitive impairment (MCI). Patients were then followed up annually during an average period of 3 years for detection of signs suggestive of a conversion to PD, DLB, or MSA. Ten healthy subjects, matched for age and gender, were submitted to a similar experimental procedure.
Standard protocol approvals, registrations, and patient consents.
The protocol was approved by the Ethics Committee of the Sacre-Coeur Hospital–University of Montreal, and all participants signed a written consent form to participate.
SPECT data acquisition and analysis.
SPECT scans with 99mcTc-ECD were performed in a 3-headed SPECT scanner (PRISM system, Picker Co.) in the morning during resting wakefulness (40 projections by scanner head, matrix of 128 × 128).
After reconstruction (filtered back projection, Butterworth filter, order: 8, cut-off: 0.39 FWHM [full width at half maximum], subtraction of 40% of the Compton window from the peak window) and attenuation correction (noniterative Chang algorithm, 0.15 cm−1), SPECT data were processed in Statistical Parametric Mapping 8. All studies were registered and normalized to a SPECT template and smoothed with a 14-mm FWHM filter. Global normalization was performed using proportional scaling. Gray matter threshold was set at 1.0.5
Differences of regional cerebral blood flow (rCBF) between groups were assessed using a 2-sample t test. Correlations between rCBF and clinical scores (UPDRS-III, FM-100, and UPSIT-12; at baseline) were assessed across all included patients (except one, because of incomplete clinical scores). In contrast to a previous study,4 clinical scores were entered in the same design matrix to ensure correlations were independent of other variables. Age and disease duration were included in the regression model. Statistical thresholds were set at p < 0.05 after correction for multiple comparisons on small volumes (sphere, 10 mm). Significant results were overlaid on an MRI template for localization of rCBF changes.
Demographic and clinical variables of IRBD patients are presented in table e-1 on the Neurology® Web site at www.neurology.org. Of 20 patients, 10 showed clinical evolution within the follow-up period (RBDEv): 5 were diagnosed with PD, and the other 5 with DLB. The 10 other patients remained in a state of isolated RBD (RBDSt). Seven RBDEv (including all those evolving to DLB) and 6 RBDSt patients had MCI at baseline.
Group comparisons of SPECT data at baseline revealed increased rCBF in the hippocampus of RBDEv bilaterally as compared with RBDSt (figure 1 and table e-2). Within RBDEv, no significant difference was observed between those evolving to PD and those converting to DLB.
Figure 1
Figure 1
Hippocampal hyperperfusion in RBDEv compared with RBDSt
Correlations at baseline between rCBF and clinical markers associated with the neurodegenerative process were looked for across all patients. UPDRS-III positively correlated with rCBF in the right hippocampus (figure 2 and table e-2). UPSIT-12 positively correlated with rCBF in the medial frontal gyrus (table e-2). FM-100 positively correlated with rCBF in the pons and left hippocampus (figure 3 and table e-2). No significant negative correlation was observed.
Figure 2
Figure 2
Correlation between motor scores (UPDRS-III) and rCBF in patients with IRBD
Figure 3
Figure 3
Correlation between color vision scores (FM-100) and rCBF in patients with IRBD
Compared with healthy controls, RBDEv showed increased perfusion in the hippocampus bilaterally as well as in the pons (table e-4 and figure e-1). No region displayed significant hypoperfusion in RBDEv compared with controls. Within RBDEv, those evolving to PD displayed increased perfusion in the hippocampus and pons, with additional hyperperfusion of the anterior cingulate cortex, whereas those evolving to DLB had only increased perfusion in the hippocampus. No significant difference of brain perfusion was found in either direction in a comparison of RBDSt with controls.
Our findings demonstrate brain perfusion patterns predicting the appearance of PD or DLB in patients with IRBD. The most consistent brain area associated with this process was the hippocampus. This structure showed increased perfusion in patients with impending conversion, not only when compared with nonevolving IRBD patients but also when compared with control subjects.
Involvement of the hippocampus in the pathophysiology of RBD is supported by both functional4 and structural brain imaging studies,6 which suggests a deep reorganization of the hippocampus in RBD. In this study, we demonstrated that hippocampal hyperperfusion was restricted to IRBD patients with future evolution to PD or DLB. Additionally, hyperperfusion of the hippocampus was correlated with worse scores on motor and color-discrimination assessments, 2 parameters associated with the transition to PD.2,7 Increased hippocampal perfusion is thus a harbinger of the neurodegenerative process leading isolated RBD to clinical PD or DLB. In line with this concept is the observation of hippocampal hyperperfusion in the initial stages of PD.8 Whether modifications of the hippocampus constitute a primary mechanism or merely reflect a corollary feature remains to be determined.
Besides the hippocampus, the pons also displayed increased perfusion in RBDEv compared with controls, in agreement with a possible dysfunction of pontine nuclei underlying the loss of REM sleep atonia.9 Correlation between decreased perfusion in the medial prefrontal cortex and impaired olfaction is in agreement with the association of olfactory disturbances with cognitive impairment observed in PD.10 It should be noted that most of our patients with RBD already had MCI at baseline, particularly those evolving to DLB, which concurs with a protracted course of cognitive impairment.
Our results thus provide the first whole-brain exploration of the functional changes associated with conversion of IRBD patients, using neuroimaging and a prospective design. The present findings converge to hippocampal hyperperfusion as a predictive imaging biomarker of the neurodegenerative evolution in RBD. 99mcTc-ECD SPECT should therefore be considered in the prognostic assessment of patients with IRBD, which might become of crucial importance in the light of future disease-modifying therapies. Although no clear difference emerged in our sample between RBD patients evolving to PD and those converting to DLB, comparison with controls suggested a more extended pattern of hyperperfusion for future PD patients. Further studies should extend these findings on larger cohorts of patients and during various states of vigilance.
Supplementary Material
Data Supplement
Accompanying Editorial
ACKNOWLEDGMENT
The authors thank Dr. Boualem Mensour for his advice on data analysis and Josie-Anne Bertrand for her help in data collection.
GLOSSARY
DLBdementia with Lewy bodies
DSM-IV-TRDiagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision
ECDethylene cysteinate dimer
FMFarnsworth-Munsell
FWHMfull width at half maximum
IRBDidiopathic REM sleep behavior disorder
MCImild cognitive impairment
MSAmultiple system atrophy
PDParkinson disease
RBDREM sleep behavior disorder
RBDEvREM sleep behavior disorder with clinical evolution
RBDStstate of isolated REM sleep behavior disorder
rCBFregional cerebral blood flow
UPDRSUnified Parkinson Disease Rating Scale
UPSIT-12University of Pennsylvania Smell Identification Test 12 items

Footnotes
Editorial, page 2296
Supplemental data at www.neurology.org
AUTHOR CONTRIBUTIONS
Dr. Dang-Vu contributed to the study concept/design, conducted data analysis and interpretation, and wrote the manuscript. Drs. Montplaisir and Gagnon contributed to the study concept/design, fundraising, and critically reviewed the manuscript. Dr. Postuma contributed to the study concept/design, participated in data collection/analysis, and critically reviewed the manuscript. Mrs. Vendette and Dr. Soucy contributed to the study concept/design and critically reviewed the manuscript.
DISCLOSURE
T.T. Dang-Vu receives support from the Canadian Institutes of Health Research, the Belgian Fonds National de la Recherche Scientifique, the Fonds Léon Frédéricq, and the Belgian College of Neuropsychopharmacology and Biological Psychiatry; and received support from the European Sleep Research Society, the Belgian American Educational Foundation, the Belgian Neurological Society, the Horlait-Dapsens Medical Foundation, and Wallonie-Bruxelles International. J.-F. Gagnon receives research support from the Canadian Institutes of Health Research (MOP-84482 [PI], MOP-62955 [co-PI], MOP-191058 [co-I], and MOP-93802 [co-PI]) and Fonds de recherche du Québec–Santé (11834 [PI]). M. Vendette reports no disclosures. J.-P. Soucy receives grants from the Canadian Institutes of Health Research (173519 [co-I], 191058 [co-I], 97865 [co-I], 102631 [co-I], 245908 [co-I], 115125 [co-PI], 259005 [co-I], and 97970 [co-I]) and from a conjoint Canadian Institutes of Health Research/Natural Sciences and Engineering Research Council of Canada program (1004158 [co-I]). R.B. Postuma receives research funds from the Weston Foundation, the Webster foundation, the Canadian Institutes of Health Research (201317 [PI], 192205 [co-PI], and 166206 [co-I]), the Fonds de recherche du Québec–Santé (9965 [PI]), and the Parkinson Society of Canada; and received funds for travel from Allergan and Novartis Canada, and speaker fees from Teva Neuroscience and Novartis Canada. J. Montplaisir receives grants from GlaxoSmithKline Pharma (PI), from the Canadian Institute of Health Research (115125 [co-I]; 102631 [PI]; 106692 [PI]; 97865 [co-I]; 62955 [PI]; 173519 [co-PI]; and 64221 [co-I]), and from Government of Canada Senior Research Chair in Sleep Medicine (PI); and received research grants/support from Merck and GlaxoSmithKline, served as an advisor for Sanofi-Aventis, Servier, Merck, Jazz Pharmaceutical, Valeant Pharmaceutical, and Impax Laboratories, and received honoraria for speaking engagements from Valeant Pharmaceutical and Otsuka Pharmaceutical. Go to Neurology.org for full disclosures.
1. Iranzo A, Molinuevo JL, Santamaria J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006;5:572–577. [PubMed]
2. Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 2011;69:811–818. [PubMed]
3. Iranzo A, Lomena F, Stockner H, et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2010;9:1070–1077. [PubMed]
4. Vendette M, Gagnon JF, Soucy JP, et al. Brain perfusion and markers of neurodegeneration in rapid eye movement sleep behavior disorder. Mov Disord 2011;26:1717–1724. [PubMed]
5. Cistaro A, Valentini MC, Chio A, et al. Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset. Eur J Nucl Med Mol Imaging 2012;39:251–259. [PubMed]
6. Scherfler C, Frauscher B, Schocke M, et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol 2011;69:400–407. [PubMed]
7. Postuma RB, Lang AE, Gagnon JF, Pelletier A, Montplaisir JY. How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain 2012;135:1860–1870. [PubMed]
8. Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N. SPECT image analysis using statistical parametric mapping in patients with Parkinson's disease. J Nucl Med 1999;40:1583–1589. [PubMed]
9. Boeve BF, Silber MH, Saper CB, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007;130:2770–2788. [PubMed]
10. Bohnen NI, Muller ML, Kotagal V, et al. Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease. Brain 2010;133:1747–1754. [PMC free article] [PubMed]
Articles from Neurology are provided here courtesy of
American Academy of Neurology