Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV

Nejad-Davarani, Siamak P.; Koeppe, Robert A.; Albin, Roger L.; Frey, Kirk A.; Müller, Martijn; Bohnen, Nicolaas I.

doi:10.1038/s41380-018-0130-5

Cited by 51 publications

(67 citation statements)

References 29 publications

(38 reference statements)

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“…A white matter reference tissue approach was used to determine VAChT binding as previously reported . This approach departs from previously used cerebellar gray matter reference regions .…”

Section: Methodsmentioning

confidence: 99%

“…This is appropriate as cholinergic terminal changes may occur in cerebellar cortices in parkinsonian disorders, which may potentially bias findings using this reference region in these particular patient populations. Distribution volume ratios (DVRs) were calculated from ratio of summed six delayed imaging frames (3 hours after injection) for gray matter target and white matter reference tissues …”

Section: Methodsmentioning

confidence: 99%

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Cholinergic system changes of falls and freezing of gait in Parkinson's disease

Bohnen

Kanel

Zhou

et al. 2019

Annals of Neurology

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112

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Objective Postural instability and gait difficulties (PIGDs) represent debilitating disturbances in Parkinson's disease (PD). Past acetylcholinesterase positron emission tomography (PET) imaging studies implicate cholinergic changes as significant contributors to PIGD features. These studies were limited in quantification of striatal cholinergic synapse integrity. Vesicular acetylcholine transporter (VAChT) PET ligands are better suited for evaluation of high binding areas. We examined associations between regional VAChT expression and freezing of gait (FoG) and falls. Methods Ninety‐four PD subjects underwent clinical assessment and VAChT ([ 18 F]FEOBV) PET. Results Thirty‐five subjects (37.2%) reported a history of falls, and 15 (16%) had observed FoG. Univariate volume‐of‐interest analyses demonstrated significantly reduced thalamic ( p = 0.0016) VAChT expression in fallers compared to nonfallers. VAChT expression was significantly reduced in the striatum ( p = 0.0012) and limbic archicortex ( p = 0.004) in freezers compared to nonfreezers. Whole‐brain voxel‐based analyses of FEOBV PET complemented these findings and showed more granular changes associated with falling history, including the right visual thalamus (especially the right lateral geniculate nucleus [LGN]), right caudate nucleus, and bilateral prefrontal regions. Freezers had prominent VAChT expression reductions in the bilateral striatum, temporal, and mesiofrontal limbic regions. Interpretation Our findings confirm and extend on previous PET findings of thalamic cholinergic deficits associated with falling history and now emphasize right visual thalamus complex changes, including the right LGN. FoG status is associated with reduced VAChT expression in striatal cholinergic interneurons and the limbic archicortex. These observations suggest different cholinergic systems changes underlying falls and FoG in PD. Ann Neurol 2019;85:538–549

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“…A white matter reference tissue approach was used to determine VAChT binding as previously reported . This approach departs from previously used cerebellar gray matter reference regions .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cholinergic system changes of falls and freezing of gait in Parkinson's disease

Bohnen

Kanel

Zhou

et al. 2019

Annals of Neurology

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133

112

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“…The novel PET tracer [ 18 F]fluoroethoxybenzovesamicol ([ 18 F]FEOBV) is a presynaptic cholinergic marker that binds to the vesicular acetylcholine transporter and therefore is expected to be a sensitive in vivo marker for cholinergic denervation. Previously, [ 18 F]FEOBV has been evaluated in Lewy body dementia, Alzheimer's disease, and healthy controls . Furthermore, [ 18 F]FEOBV was implemented in PD research by evaluating the role of vesicular acetylcholine transporter binding in the clinical symptomology of falling and freezing .…”

Section: Group Difference and Test‐retest Variability For [18f]feobv mentioning

confidence: 99%

“…No partial volume correction was performed. A standard uptake values ratio (SUVr) was generated using the supratentorial white matter as a reference region . The volume of interest analysis was performed using an a priori set of standard volumes of interest, automatically adjusted to the subject's anatomy.…”

Section: Group Difference and Test‐retest Variability For [18f]feobv mentioning

confidence: 99%

[¹⁸F]Fluoroethoxybenzovesamicol in Parkinson's disease patients: Quantification of a novel cholinergic positron emission tomography tracer

et al. 2019

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“…Mapping of brain acetylcholinesterase (ACHE) showed alterations in cortical and subcortical levels in both PDD and DLB [49,50]. Recent PET studies of the vesicular ACh transporter (VAChT) showed more extensive reductions affecting neocortical, limbic and thalamic regions in DLB than in AD [51]. 11C PIB-PET imaging showed more frequent and severe Aβ brain deposition in DLB than in PDD [52,53], predictive of faster degeneration in cortex and striatum [54].…”

Section: Pathophysiology Of Cognitive Impairmentmentioning

confidence: 99%

Dementia with Lewy Bodies and Parkinson's Disease-Dementia: Current Perspectives

A¹

2018

Int J Neurol Neurother

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Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD) are two closely related major neurocognitive disorders with Lewy bodies of unknown etiology, showing notable overlap in their clinical presentation, pathological features, biochemistry, and genetic risk factors. According to international consensus, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia preceding parkinsonism in DLB, while it develops after onset of parkinsonism in PDD (the one-year rule). Clinically, both syndromes show cognitive impairment with severe deficits in executive function, visuo-spatial processing, fluctuating attention and parkinsonism, with higher prevalence of Alzheimer-type lesions in DLB that may account for earlier onset and severity of cognitive deficits. These are also associated with multiple neurotransmitter deficits indicating that cognitive impairment in Lewy body disesses is multifactorial. Recent intra vitam neuroimaging, clinico-pathological studies and animal models suggest that DLB and PDD represent closely related but different, heterogenic subtypes of an α-synuclein-associated disease spectrum (Lewy body diseases) or parts of a continuum with PDD at the mild end of the spectrum, DLB in the middle, and DLB+AD at the more severe end. In view of the controversies about the nosology of both disorders, continuous effort is necessary to differentiate them more clearly and to clarify the underlying pathogenic mechanisms in order to enable effective mechanistic-based treatment, while, currently, no disease-modifying therapies are available.

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Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV

Cited by 51 publications

References 29 publications

Cholinergic system changes of falls and freezing of gait in Parkinson's disease

Cholinergic system changes of falls and freezing of gait in Parkinson's disease

[¹⁸F]Fluoroethoxybenzovesamicol in Parkinson's disease patients: Quantification of a novel cholinergic positron emission tomography tracer

Dementia with Lewy Bodies and Parkinson's Disease-Dementia: Current Perspectives

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Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV

Cited by 51 publications

References 29 publications

Cholinergic system changes of falls and freezing of gait in Parkinson's disease

Cholinergic system changes of falls and freezing of gait in Parkinson's disease

[18F]Fluoroethoxybenzovesamicol in Parkinson's disease patients: Quantification of a novel cholinergic positron emission tomography tracer

Dementia with Lewy Bodies and Parkinson's Disease-Dementia: Current Perspectives

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[¹⁸F]Fluoroethoxybenzovesamicol in Parkinson's disease patients: Quantification of a novel cholinergic positron emission tomography tracer