Functional connectivity in dementia with Lewy bodies: A within‐ and between‐network analysis

Schumacher, Julia; Peraza, Luis R.; Firbank, Michael; Thomas, Alan; Kaiser, Marcus; Gallagher, Peter; O’Brien, John T.; Blamire, Andrew M.; Taylor, John‐Paul

doi:10.1002/hbm.23901

Cited by 64 publications

(90 citation statements)

References 60 publications

(96 reference statements)

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“…So far, the assessment of functional connectivity in DLB was based mostly on rs‐fMRI studies, showing heterogeneous results (Franciotti et al, ; Galvin et al, ; Kenny et al, ; Kenny et al, ; Kobeleva et al, ; Lowther et al, ; Peraza et al, ; Schumacher et al, ; Sourty et al, ). We have previously provided thorough evidence for both local and distributed brain metabolic alterations characterizing brain connectomics in DLB, crucially mirroring the underlying pathology and neurodegeneration (Caminiti, Tettamanti, et al, ).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…We believe that a significant limitation of our model concerns the conceptualization of SFDs. Although decoupling of DMN to form random connections seems to many to be a reasonable account of hallucinations, it is less convincing as an account of SFDs or delusions, which, according to the main objections, remain fixed over a long period or are seen in younger patients or are considered a negligible feature of PD or are considered indistinguishable from somatic hallucinations. The nosologic entity of SFDs is still unresolved and a matter of lively debate between movement disorder specialists and psychiatrists.…”

Section: Implications For Future Studies and Therapeutic Effortsmentioning

confidence: 99%

“…The positron emission tomography sign refers to the presence of a restricted area of preserved activity, localized in the PCC, that is embedded in hypoactive cortical regions. Further evidence is provided by several functional magnetic resonance imaging (fMRI) studies performed at rest and during tasks that show altered DMN activity and/or connectivity in PD and DLB patients that exhibit simpleor complex hallucinations (Table ). Moreover, structural MRI studies have lent support to the idea that altered activity/connectivity and decoupling of the DMN in PD‐DLB is of a functional rather than an anatomical character .…”

Section: Anatomical Pathophysiological Overlaps and Mechanismsmentioning

confidence: 99%

Hallucinations, somatic‐functional disorders of PD‐DLB as expressions of thalamic dysfunction

et al. 2019

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Hallucinations, delusions, and functional neurological manifestations (conversion and somatic symptom disorders) of Parkinson's disease (PD) and dementia with Lewy bodies increase in frequency with disease progression, predict the onset of cognitive decline, and eventually blend with and are concealed by dementia. These symptoms share the absence of reality constraints and can be considered comparable elements of the PD‐dementia with Lewy bodies psychosis. We propose that PD‐dementia with Lewy bodies psychotic disorders depend on thalamic dysfunction promoting a theta burst mode and subsequent thalamocortical dysrhythmia with focal cortical coherence to theta electroencephalogram rhythms. This theta electroencephalogram activity, also called fast‐theta or pre‐alpha, has been shown to predict cognitive decline and fluctuations in Parkinson's disease with dementia and dementia with Lewy bodies. These electroencephalogram alterations are now considered a predictive marker for progression to dementia. The resulting thalamocortical dysrhythmia inhibits the frontal attentional network and favors the decoupling of the default mode network. As the default mode network is involved in integration of self‐referential information into conscious perception, unconstrained default mode network activity, as revealed by recent imaging studies, leads to random formation of connections that link strong autobiographical correlates to trivial stimuli, thereby producing hallucinations, delusions, and functional neurological disorders. The thalamocortical dysrhythmia default mode network decoupling hypothesis provides the rationale for the design and testing of novel therapeutic pharmacological and nonpharmacological interventions in the context of PD, PD with dementia, and dementia with Lewy bodies. © 2019 International Parkinson and Movement Disorder Society

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“…A recent study by Schumacher et al aimed to explore within- and between-network connectivity in a range of resting state networks, being the first to investigate how DLB affects connectivity between these resting state networks [39]. DLB patients displayed more decreases in within-network connectivity compared to controls, primarily in temporal, motor and frontal networks.…”

Section: Functional Imagingmentioning

confidence: 99%

“…DLB patients displayed more decreases in within-network connectivity compared to controls, primarily in temporal, motor and frontal networks. In contrast, long-range functional connectivity appeared to be intact in DLB, with increased connectivity only identified between a frontal and a temporal network [39]. Only subtle differences were observed when AD and DLB were compared, suggesting a potential overlap in their resting state functional connectivity.…”

Section: Functional Imagingmentioning

confidence: 99%

Neuroimaging in Lewy body dementia

Yousaf¹,

Dervenoulas

Valkimadi

et al. 2018

J Neurol

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Lewy body dementia (DLB) is a common form of cognitive impairment, accounting for 30% of dementia cases in ages over 65 years. Early diagnosis of DLB has been challenging; particularly in the context of differentiation with Parkinson's disease dementia and other forms of dementias, such as Alzheimer's disease and rapidly progressive dementias. Current practice involves the use of [I]FP-CIT-SPECT, [F]FDG PET and [I]MIBG molecular imaging to support diagnostic procedures. Structural imaging techniques have an essential role for excluding structural causes, which could lead to a DLB-like phenotype, as well as aiding differential diagnosis through illustrating disease-specific patterns of atrophy. Novel PET molecular imaging modalities, such as amyloid and tau imaging, may provide further insights into DLB pathophysiology and may aid in early diagnosis. A multimodal approach, through combining various established techniques and possibly using novel radioligands, might further aid towards an in-depth understanding of this highly disabling disease. In this review, we will provide an overview of neuroimaging applications in patients with DLB.

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Functional connectivity in dementia with Lewy bodies: A within‐ and between‐network analysis

Cited by 64 publications

References 60 publications

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

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

Hallucinations, somatic‐functional disorders of PD‐DLB as expressions of thalamic dysfunction

Neuroimaging in Lewy body dementia

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