Project - Clinical, sleep and neuroimaging biomarkers of progression along the Lewy body disorder continuum
Project tag with a disease
RBD, DLB, PD
Research Project Description
Lewy body disorders which include Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) represent the second most common cause of neurodegeneration in the ageing population. These illnesses are characterized by the abnormal deposition of protein aggregates called Lewy bodies found inside the cell body. Clinically both disorders share a wide range of motor and non-motor features and predictably lead to severe disability, caregiver burden and nursing home placement yet they differ in the prominence of symptoms and rate of functional decline. Unfortunately, we currently have no objective way of diagnosing and predicting Lewy body disorders, frequently leading to delayed or incorrect diagnoses and stifling efforts to develop disease-modifying treatments.
Interestingly, in the last two decades we have learnt that in patients who develop a disorder known as REM sleep behaviour disorder (RBD) defined as the loss of the normal paralysis during sleep (causing affected patients to ‘act out their dreams’) almost always go on to develop PD or DLB (>90% over 15 years). It is also increasingly recognized that RBD is the most common predictive marker of Lewy body pathology in the brain. This discovery offers a unique window for understanding the natural progression of Lewy body disorders but also for potentially trialling neuroprotective treatments.
In this project, we have recruited patients with idiopathic RBD, PD and DLB as well as healthy controls. We are currently studying cross-sectional differences in clinical and neuropsychometric measurements, structural and functional MRI, quantitative EEG, and circadian markers both in isolation and in combination to understand the signatures of Lewy body pathology generally which may be predictors of transition in the RBD cohort. We also aim to continue to use these measures as part of a longitudinal international multicentre biobanking program to be mobilized for future disease modifying clinical trials.
Key Publications from this project
- Matar E, White SR, Taylor JP, Thomas A, McKeith IG, Kane JPM, Surendranathan AJ, Halliday GM, Lewis SJG, O’Brien JT (2021). Progression of clinical features in Lewy body dementia can be detected over six months - Analysis of a multi-centre randomized controlled trial. Neurology (Accepted).
- Matar E, Ehgoetz Martens K, Phillips J, Halliday GM, Lewis SJG (2021). Dynamic network impairments underlie cognitive fluctuations in Lewy body dementia. Nature Parkinson’s Disease (Accepted).
- Matar E, Lewis SJG, McCarter SJ, St Louis EJ, Videnovic A (2021). Current concepts and controversies in the management of REM sleep behavior disorder. Neurotherapeutics. Jan 6. doi: 10.1007/s13311-020-00983-7. Epub ahead of print. PMID: 33410105.
- Powell A, Matar E, Lewis SJG (2021). Treating hallucinations in Parkinson's disease. Expert Rev Neurother. Dec 14:1-14. doi: 10.1080/14737175.2021.1851198. Epub ahead of print. PMID: 33183105.
- Rahayel S, Postuma RB, Montplaisir JY, Misic B, Tremblay C, Vo A, Lewis SJG, Matar E, Ehgoetz Martens KA, Blac, F, Yao C, Pelletier A, Gaubert M, Carrier J, Monchi O, Chouinard S, Panisset M, Dagher A, Gagnon JF (2021). A prodromal brain-clinical pattern of cognition in synucleinopathies. Ann Neurol. Feb;89(2):341-357.
- Burgess A, Van Diggele C, Matar E (2020). Interprofessional Team-based learning: building social capital. Journal of Medical Education and Curricular Development. J Med Educ Curric Dev. Aug 7;7:2382120520941820.
- Ehgoetz Martens K*, Matar E*, Shine JM, Phillips J, Georgiades MJ, Grunstein RR, Halliday GM, Lewis SJG (2020). The neural signature of impaired dual tasking in Idiopathic REM sleep behavior disorder patients. Movement Disorders (Accepted Feb 2020).
- Chiu NKH, Ehgoetz Martens KA, Mok VCT, Lewis SJG, Matar E (2020). Prevalence and predictors of mood disturbances in idiopathic REM sleep behaviour disorder. J Sleep Res. Apr 7:e13040. doi: 10.1111/jsr.13040. Online ahead of print. PMID: 32255236
- Matar E, Shine JM, Halliday GM, Lewis SJG (2020). Cognitive fluctuations in Lewy body dementia – Towards a pathophysiological framework. Brain Jan 1;143(1):31-46. doi: 10.1093/brain/awz311
- Matar E, Phillips J, Ehgoetz Martens K, Halliday GM, Lewis SJG (2020). Clinical features of Lewy body dementia: insights into diagnosis and pathophysiology. J Neurol. Feb;267(2):380-389
- Phillips JR, Matar E, Martens KAE, Halliday GM, Moustafa AA, Lewis SJG (2019). Evaluating the Sustained Attention Response Task to Quantify Cognitive Fluctuations in Dementia With Lewy Bodies. J Geriatr Psychiatry Neurol. 2019 Oct 31:891988719882093. doi: 10.1177/0891988719882093.
- Raupach AK, Ehgoetz Martens KA, Memarian N, Zhong G, Matar E, Halliday GM, Grunstein R, Lewis SJG. (2020) Assessing the role of nocturnal core body temperature dysregulation as a biomarker of neurodegeneration. J Sleep Res. 2019 Nov 11:e12939. doi: 10.1111/jsr.12939. Online ahead of print. PMID: 31713306
- Burgess A, Matar E, Neuen B, Fox G (2019). A longitudinal faculty program: supporting a culture of teaching. BMC Medical Education Nov 1;19(1):400.
- Ehgoetz Martens KA, Matar E, Hall JM, Phillips J, Szeto JYY, Gouelle A, Grunstein RR, Halliday GM, Lewis SJG. (2019). Subtle gait and balance impairments occur in idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2019 Jun 26.
- Matar E, Phillips J, Ehgoetz Martens K, Halliday GM, Lewis SJG. Impaired colour discrimination – A specific marker of Hallucinations in Lewy body disorders. Journal of Geriatric Psychiatry and Neurology. 2019 Apr 29: DOI: 891988719845501
- Shine JM, Bell PT, Matar E, Poldrack RA, Lewis SJG, Halliday GM, O'Callaghan C. Dopamine depletion alters macroscopic network dynamics in Parkinson's disease. Brain. 2019 Apr 1;142(4):1024-1034.
Project related links
For further reading on the link between RBD and neurodegeneration, you can access our review in the Medical Journal of Australia:
Information for those wishing to be involved in any of our studies can contact our research clinic through here