Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs

Kanel, Prabesh; Müller, Martijn; Zee, Sygrid van der; Sanchez-Catasus, Carlos A.; Koeppe, Robert A.; Frey, Kirk A.; Bohnen, Nicolaas I.

doi:10.1176/appi.neuropsych.19070165

Cited by 25 publications

(24 citation statements)

References 33 publications

(36 reference statements)

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“…Higher than normal range binding in these regions suggests a compensatory cholinergic upregulation associated with the initial phases of Lewy body neurodegenerations. Our voxel-based VAChT PET changes showed evidence of cholinergic vulnerability of key hub regions of different large scale neural networks in LBD [31]. Further research is needed to determine whether cholinergic changes in brain regions that spatially overlap with key hubs in important large-scale brain networks may result in altered compensatory or decompensatory functions of such networks…”

Section: Bidirectional Spatial Covariance Changes Suggest Possible Cholinergic Compensatory Processesmentioning

confidence: 85%

“…The spatial pattern of the observed cholinergic vulnerability may involve key hubs of large-scale neural networks including the cingulo-opercular, visual attention, saliency and spatial navigation networks. These topographic changes may suggest a cholinergic vulnerability underlying clinical phenotypic features, such as fluctuating cognition, falls and visuospatial/visuoperceptual cognitive in LBD [31].…”

Section: Spatial Covariance Studies Suggest Cholinergic Contributions To Large Scale Neural Network Changes In Dementiamentioning

confidence: 99%

“…We recently reported on topographic cholinergic changes in patients with LBD using VAChT PET [31]. Binding reductions were prominent in anterior-to-mid cingulate cortices, bilateral insula, right more than left lateral geniculate nuclei, bilateral anterior and superior thalami, and posterior hippocampal fimbria and fornices.…”

Section: Spatial Covariance Studies Suggest Cholinergic Contributions To Large Scale Neural Network Changes In Dementiamentioning

confidence: 99%

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New Developments in Cholinergic Imaging in Alzheimer and Lewy Body Disorders

Craig

Ray

Müller

et al. 2020

Curr Behav Neurosci Rep

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Purpose of Review This paper aims to review novel trends in cholinergic neuroimaging in Alzheimer and Lewy body parkinsonian disorders. Recent FindingsThe spectrum of cholinergic imaging is expanding with the availability of spatially more precise radioligands that allow assessment of previously less recognized subcortical and cortical structures with more dense cholinergic innervation. In addition, advances in MRI techniques now allow quantitative structural or functional assessment of both the cholinergic forebrain and the pedunculopontine nucleus, which may serve as non-invasive prognostic predictors. Multimodal imaging approaches, such as PET-MRI or multiligand PET offer new insights into the dynamic and interactive roles of the cholinergic system at both local and larger-scale neural network levels.Summary Our understanding of the heterogeneous roles of the cholinergic system in age-related diseases is evolving. Multimodal imaging approaches that provide complimentary views of the cholinergic system will be necessary to shed light on the impact of cholinergic degeneration on regional and large-scale neural networks that underpin clinical symptom manifestation in neurodegeneration.

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Section: Bidirectional Spatial Covariance Changes Suggest Possible Cholinergic Compensatory Processesmentioning

confidence: 85%

Section: Spatial Covariance Studies Suggest Cholinergic Contributions To Large Scale Neural Network Changes In Dementiamentioning

confidence: 99%

Section: Spatial Covariance Studies Suggest Cholinergic Contributions To Large Scale Neural Network Changes In Dementiamentioning

confidence: 99%

See 1 more Smart Citation

New Developments in Cholinergic Imaging in Alzheimer and Lewy Body Disorders

Craig

Ray

Müller

et al. 2020

Curr Behav Neurosci Rep

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“…Loss of ChAT activity in neocortical areas in patients with combined AD and DLBD pathology was greater than that in pure AD (Tiraboschi et al., 2002). Positron emission tomography (PET) imaging with the vesicular acetylcholine transporter has confirmed cholinergic loss in the opercular regions, cingulate cortex, and insular cortex in DLBD (Kanel et al., 2020). The Ch4‐nbM neurons are vulnerable to the accumulation of LB and α‐synuclein in DLBD (Graeber & Muller, 2003) (Figure 3f), and significant loss of Ch4‐nbM neurons has been reported in PD with or without dementia (Gasper & Gray, 1984; Liu et al., 2015; Whitehouse et al., 1983).…”

Section: Basal Forebrain Cholinergic System In Dementiamentioning

confidence: 99%

Basal forebrain cholinergic system in the dementias: Vulnerability, resilience, and resistance

Geula

Dunlop

Ayala

et al. 2021

Journal of Neurochemistry

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The basal forebrain cholinergic neurons (BFCN) provide the primary source of cholinergic innervation of the human cerebral cortex. They are involved in the cognitive processes of learning, memory, and attention. These neurons are differentially vulnerable in various neuropathologic entities that cause dementia. This review summarizes the relevance to BFCN of neuropathologic markers associated with dementias, including the plaques and tangles of Alzheimer's disease (AD), the Lewy bodies of diffuse Lewy body disease, the tauopathy of frontotemporal lobar degeneration (FTLD‐TAU) and the TDP‐43 proteinopathy of FTLD‐TDP. Each of these proteinopathies has a different relationship to BFCN and their corticofugal axons. Available evidence points to early and substantial degeneration of the BFCN in AD and diffuse Lewy body disease. In AD, the major neurodegenerative correlate is accumulation of phosphotau in neurofibrillary tangles. However, these neurons are less vulnerable to the tauopathy of FTLD. An intriguing finding is that the intracellular tau of AD causes destruction of the BFCN, whereas that of FTLD does not. This observation has profound implications for exploring the impact of different species of tauopathy on neuronal survival. The proteinopathy of FTLD‐TDP shows virtually no abnormal inclusions within the BFCN. Thus, the BFCN are highly vulnerable to the neurodegenerative effects of tauopathy in AD, resilient to the neurodegenerative effect of tauopathy in FTLD and apparently resistant to the emergence of proteinopathy in FTLD‐TDP and perhaps also in Pick's disease. Investigations are beginning to shed light on the potential mechanisms of this differential vulnerability and their implications for therapeutic intervention.

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“…Voxel-based PET analysis was performed as previously described. 34 All brain images were spatially normalized to Montreal Neurological Institute template space using the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) normalization protocol 35 and smoothed with a Gaussian kernel of 8 mm full width half maximum to adjust the anatomical variability between the individual brains and to enhance the signal-to-noise ratio. The relevant brain areas were displayed in Montreal Neurological Institute atlas coordinates (in millimeters) in the stereotactic space using the automated anatomical labeling toolbox.…”

Section: Voxel-based Pet Analysismentioning

confidence: 99%

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

et al. 2020

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Background The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes. Objective The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD. Methods A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age‐matched, gender‐matched, and educational level–matched control group. Correlations between domain‐specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease‐specific versus normal aging effects. Results Voxel‐based whole‐brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus. Conclusion Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease‐specific and aging effects. © 2020 International Parkinson and Movement Disorder Society

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Topography of Cholinergic Changes in Dementia With Lewy Bodies and Key Neural Network Hubs

Cited by 25 publications

References 33 publications

New Developments in Cholinergic Imaging in Alzheimer and Lewy Body Disorders

New Developments in Cholinergic Imaging in Alzheimer and Lewy Body Disorders

Basal forebrain cholinergic system in the dementias: Vulnerability, resilience, and resistance

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

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