PET study of brain acetylcholinesterase in cerebellar degenerative disorders

Hirano, Shigeki; Shinotoh, Hitoshi; Arai, Kimihito; Aotsuka, Akiyo; Yasuno, Fumihiko; Tanaka, Noriko; Ota, Tsuneyoshi; Sato, Kōichi; Fukushi, Kiyoshi; Tanada, Shuji; Hattori, Takamichi; Irie, Toshiaki

doi:10.1002/mds.22056

Cited by 32 publications

(23 citation statements)

References 28 publications

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“…The absence of cortical cholinergic denervation in both Ch4 and Ch1 cholinergic pathways is in agreement with recent findings in MSA patients showing normal in vivo brain AChE activity (Hirano et al, 2008), however not reported in another study (Gilman et al, 2010). …”

Section: Discussionsupporting

confidence: 93%

[123I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5–Ch6)

Mazère

Meissner

Sibon

et al. 2013

NeuroImage: Clinical

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We evaluated in vivo the integrity of brain cholinergic pathways in Multiple System Atrophy (MSA) and the relationship between cholinergic dysfunction and motor disturbances, by measuring the vesicular acetylcholine transporter (VAChT) expression using Single Photon Emission Computed Tomography (SPECT) and [123I]-iodobenzovesamicol ([123I]-IBVM).MethodsNine patients with probable MSA and 12 healthy volunteers underwent a dynamic [123I]-IBVM SPECT–CT scan and a magnetic resonance imaging (MRI) scan. All patients were examined with the Unified MSA Rating Scale (UMSARS; subscale I = activities of daily living (ADL), II = motor and IV = disability). CT and MRI images were used to register the dynamic SPECT image to the Montreal Neurological Institute brain template, which includes the regions of interest (ROI) of striatum and Ch1 (medial septum nucleus-hippocampus), Ch4 (nucleus basalis of Meynert-cortex) and Ch5–Ch6 (pedunculopontine and laterodorsal tegmental nuclei-thalamus) cholinergic pathways. For each ROI, pharmacokinetic modeling of regional time activity curves led to the calculation of [123I]-IBVM to VAChT binding potential (BPND) value, proportional to VAChT expression.ResultsWhen compared to controls, BPND values for MSA in Ch5–Ch6 were significantly decreased in both the pedunculopontine–laterodorsal nuclei and the thalamus (p = 0.004 and p = 0.006, respectively). Additionally, thalamus BPND values were correlated with UMSARS ADL (p = 0.006), motor (p = 0.002) and disability (p = 0.02) sub-scores. UMSARS motor subscale items 13 (postural instability) and 14 (gait) were also correlated with thalamus BPND values (p = 0.04).ConclusionCh5–Ch6 are the most affected cholinergic pathways in MSA at both cell bodies and thalamic cholinergic terminals. These results underscore the relevant role of [123I]-IBVM SPECT for improving our understanding of the pathophysiology in MSA.

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Section: Discussionsupporting

confidence: 93%

[123I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5–Ch6)

Mazère

Meissner

Sibon

et al. 2013

NeuroImage: Clinical

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“…In summary, distinct cerebellar subregional metabolic alterations among different types of cerebellar ataxia were attributable to the distinctive neuropathological changes in cerebellum, as reported in previous studies with acetylcholinesterase and DAT PET [40, 41]. In contrast, patients with CCD, characterized by functional impairment in a region far from the site of a brain lesion that is anatomically connected by fiber tracts [42], showed relatively preserved metabolism in the anterior lobe resulting in high anterior-posterior lobe ratio.…”

Section: Discussionsupporting

confidence: 70%

“…At the start of the present study, choosing a specific supratentorial region as a reference for count normalization presented a challenge as previous reports indicated that not only cerebellar but also cerebral regions were involved in SCA as determined by 18 F-FDG PET [36, 40, 48]. Thus, we choose an area with minimal changes among disease groups and controls using voxelwise analysis.…”

Section: Discussionmentioning

confidence: 99%

Different subregional metabolism patterns in patients with cerebellar ataxia by 18F-fluorodeoxyglucose positron emission tomography

Kim

et al. 2017

PLoS ONE

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We evaluated cerebellar subregional metabolic alterations in patients with cerebellar ataxia, a representative disease involving the spinocerebellum. We retrospectively analyzed 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images in 44 patients with multiple system atrophy of the cerebellar type (MSA-C), 9 patients with spinocerebellar ataxia (SCA) type 2, and 14 patients with SCA type 6 and compared with 15 patients with crossed cerebellar diaschisis (CCD) and 89 normal controls. Cerebellar subregional metabolism was assessed using 13 cerebellar subregions (bilateral anterior lobes [ANT], superior/mid/inferior posterior lobes [SUPP/MIDP/INFP], dentate nucleus [DN], anterior vermis [ANTV], and superior/inferior posterior vermis [SUPV/INFV]) to determine FDG uptake ratios. MSA-C and SCA type 2 showed severely decreased metabolic ratios in all cerebellar subregions compared to normal controls (ANT, 0.58 ± 0.08 and 0.50 ± 0.06 vs. 0.82 ± 0.07, respectively, p < 0.001). SCA type 6 showed lower metabolic ratios in almost all cerebellar subregions (ANT, 0.57 ± 0.06, p < 0.001) except INFV. Anterior-posterior lobe ratio measurements revealed that SCA type 2 (Right, 0.81 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.83 ± 0.05 vs. 0.88 ± 0.04, p = 0.003) and SCA type 6 (Right, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001; Left, 0.72 ± 0.05 vs. 0.88 ± 0.04, p < 0.001) showed preferential hypometabolism in the anterior lobe compared to normal controls, which was not observed in CCD and MSA-C. Asymmetric indices were higher in CCD and MSA-C than in normal controls (p < 0.001), whereas such differences were not found in SCA types 2 and 6. In summary, quantitative analysis of cerebellar subregional metabolism ratios revealed preferential involvement of the anterior lobe, corresponding to the spinocerebellum, in patients with cerebellar ataxia, whereas patients with CCD and MSA-C exhibited more asymmetric hypometabolism in the posterior lobe.

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“…Healthy controls and image analysis were different among the studies. CBS, corticobasal syndrome23; DLB, dementia with Lewy bodies24; EOAD, early onset Alzheimer's disease25; FTD, frontotemporal dementia23; FTDP17, frontotemporal dementia and parkinsonism linked to chromosome 1726; LOAD, late onset Alzheimer's disease25; MSA-C, cerebellar variant of multiple system atrophy27; MSA-P, parkinsonian variant of multiple system atrophy28; PDND, Parkinson's disease with no dementia24; PDD, Parkinson's disease with dementia24; PSP, progressive supranuclear palsy23; SCA3, spinocerebellar ataxia type 327; SCA6, spinocerebellar ataxia type 6 27…”

Section: Cholinergic Neuroimaging In Pd and Related Disordersmentioning

confidence: 99%

Functional brain imaging of cognitive dysfunction in Parkinson's disease

Hirano

Shinotoh

Eidelberg

2012

J Neurol Neurosurg Psychiatry

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Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

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PET study of brain acetylcholinesterase in cerebellar degenerative disorders

Cited by 32 publications

References 28 publications

[123I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5–Ch6)

[123I]-IBVM SPECT imaging of cholinergic systems in multiple system atrophy: A specific alteration of the ponto-thalamic cholinergic pathways (Ch5–Ch6)

Different subregional metabolism patterns in patients with cerebellar ataxia by 18F-fluorodeoxyglucose positron emission tomography

Functional brain imaging of cognitive dysfunction in Parkinson's disease

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