Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas–Antonios; Szewczyk-Królikowski, Konrad; Menke, Ricarda; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes; Mackay, Clare E.; Hu, Michele T.M.

doi:10.1093/brain/aww124

Cited by 113 publications

(112 citation statements)

References 46 publications

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“…One possibility is that this form of aberrant connectivity only appears later in the course of PD. In fact, it was shown earlier that reductions in BG connectivity seen in RBD patients closely resemble those recorded from de novo PD patients (Rolinski et al, 2016). Thus, increased functional connectivity may constitute a pathophysiological feature appearing only later in the course of the disease.…”

Section: Discussionmentioning

confidence: 68%

“…We focused on functional connectivity with the putamen for two reasons. First, the putamen as its interactions with other cortical and subcortical regions have been consistently shown to be disrupted in the prodromal phase of PD (Ellmore et al, 2013; Rolinski et al, 2016). Second, as cortical input to the BG passes through the striatum, disruptions in cortical-BG interactions, if such indeed exist, should be reflected in functional connectivity between cortical regions and the putamen.…”

Section: Resultsmentioning

confidence: 99%

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Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

Dayan

Browner

2017

Preprint

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Although the diagnosis of Parkinson’s disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.

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Section: Discussionmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

Dayan

Browner

2017

Preprint

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“…In addition, connectivity analysis allowed to reveal novel neural alterations associated with RBD, that is, patients with RBD showed a widespread loss of integrity of attention large‐scale networks (Figure a), and a modulation in between‐networks interactions, with significantly strengthen association between basal ganglia, limbic, and attention networks (Figure b). Previous studies also reported functional connectivity alterations in the basal ganglia of subjects with idiopathic RBD (Ellmore et al, ; Rolinski et al, ). Considering that prevalence of parkinsonism did not differ between DLB–RBD+ and DLB–RBD− groups, we suggest that RBD is intrinsically associated with connectivity changes in the basal ganglia networks, independently of motor impairment.…”

Section: Discussionmentioning

confidence: 77%

Vulnerability of multiple large‐scale brain networks in dementia with Lewy bodies

Sala

Caminiti

Iaccarino

et al. 2019

Human Brain Mapping

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Aberrations of large‐scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed‐based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large‐scale resting‐state networks' integrity and their interactions. We found both local and long‐distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network‐level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network‐level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder.

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“…Abnormalities of resting-state MRI, consistent with loss of a basal ganglia functional network, were also described in RBD subjects and on the first analysis were able to distinguish RBD patients from controls with 96% sensitivity and 74% specificity. 99 Other MRI studies reported atrophy on voxel-based morphometry, cortical thinning, shape deformation of subcortical structures, and abnormal diffusion tensor imaging in RBD patients; these have not yet been proven to predict disease. 85,100 Outside RBD, MRI abnormalities were also noted in asymptomatic LRRK2 carriers, again without prospective confirmation of predictive value.…”

Section: Neuroimaging Catches Upmentioning

confidence: 99%

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

2019

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The past decade has seen a dramatic expansion of the field of prodromal PD. Ten years ago, there were only six known prodromal markers of disease, none of which had more than two studies documenting diagnostic value. We now have at least 16 markers, with as many as 10 prospective studies for a single marker. This review summarizes the major advances over the last decade and speculates about the advances we will see in the decade to come. The most notable advances over the last decade came through the study of high‐risk cohorts (REM sleep behavior disorder and later genetic and autonomic cohorts), the generation of more representative population‐based cohorts for studying prodromal PD, major advances in neuroimaging of early disease stages, the emerging likelihood that tissue biopsy will be able to diagnose prodromal PD, and the coalescence of prodromal markers into discrete criteria. As the next decade dawns, we await increasing precision of sensitivity and specificity estimates of known markers, the discovery of new biomarkers of prodromal disease, improvements in diagnosis using combined methods/criteria (with increasing recognition of prodromal PD as one stage of the full PD spectrum), and ultimately the development of neuroprotective therapy that can be provided at the earliest stages of disease. © 2019 International Parkinson and Movement Disorder Society

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Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

Cited by 113 publications

References 46 publications

Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

Vulnerability of multiple large‐scale brain networks in dementia with Lewy bodies

Prodromal Parkinson's Disease: The Decade Past, the Decade to Come

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