Mesopontine cholinergic neuron involvement in Lewy body dementia and multiple system atrophy

Schmeichel, Ann M.; Buchhalter, L. C.; Low, P. A.; Parisi, Joseph E.; Boeve, Bradley; Sandroni, Paola; Benarroch, Eduardo E.

doi:10.1212/01.wnl.0000298691.71637.96

Cited by 107 publications

(72 citation statements)

References 22 publications

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“…30 Ascending cholinergic pathways from the pedunculopontine nucleus and laterodorsal tegmental nuclei are involved in arousal. 31 The loss of these projections has been described in DLB, but neuronal counts did not correlate with sleep disturbances or fluctuations. DLB is associated with greater attentional deficits compared with AD 32 ; however, loss of attentional control is also an early finding in AD.…”

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confidence: 92%

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Escandon

Al-Hammadi²,

Galvin³

2010

Neurology

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confidence: 92%

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Escandon

Al-Hammadi²,

Galvin³

2010

Neurology

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“…33 Besides the dopaminergic neurons of substantia nigra, the cholinergic neurons in the dorsal mesopontine nuclei, specifically the pedunculopontine tegmental and lateral dorsal tegmental nuclei, are involved with the LB-related pathology with significant loss of cholinergic neurons. 33,35 Degeneration in the dorsal mesopontine region may involve other neurotransmitter systems including the noradrenergic system because of degeneration in the locus coeruleus and the serotonergic system via damage to the dorsal raphe nu- clei. 36,37 The mesopontine nuclei are also affected in AD, [37][38][39] although there is some evidence that they are more affected in DLB than in AD.…”

Section: Resultsmentioning

confidence: 99%

Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies

2012

Neurology

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Objective: To determine the association between the focal atrophy measures on antemortem MRI and postmortem neuropathologic classification of dementia with Lewy bodies (DLB) using the Third Report of the DLB Consortium criteria. Methods:We retrospectively identified 56 subjects who underwent antemortem MRI and had Lewy body (LB) pathology at autopsy. Subjects were pathologically classified as high (n ϭ 25), intermediate (n ϭ 22), and low likelihood DLB (n ϭ 9) according to the Third Report of the DLB Consortium criteria. We included 2 additional pathologic comparison groups without LBs: one with low likelihood Alzheimer disease (AD) (control; n ϭ 27) and one with high likelihood AD (n ϭ 33). The associations between MRI-based volumetric measurements and the pathologic classification of DLB were tested with analysis of covariance by adjusting for age, sex, and MRI-to-death interval. Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer disease (AD); however, many patients with DLB also have AD pathology. [1][2][3][4][5] Imaging markers that predict the contribution of AD to the dementia syndrome in DLB would have an important role in treatment decisions and assessing responsiveness to treatments targeting disease-specific pathologies. Results:According to the Third Report of the DLB Consortium criteria, 6 the pathologic diagnosis of DLB is made by considering both AD and Lewy body (LB) pathologies. For example, patients with limbic LBs are diagnosed as high likelihood DLB if they have low likelihood AD, but diagnosed as low likelihood DLB if they have high likelihood AD. Therefore, in vivo identification of AD and LB pathology is critical for the differential diagnosis of DLB.

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“…Recent studies have shown hypocretinergic cell loss in the lateral hypothalamus of patients with Parkinson's disease, which could contribute to the 'narcoleptic-like' features in PDD and DLB [30] . The pathology of cognitive fluctuations has been suggested to be localized in the isodendritic core, a small group of nuclei in the brainstem and basal forebrain that forms part of the reticular activating system and includes the locus coeruleus, raphe nuclei and the basal nucleus of Meynert [31] and more recently specifically to the pedunculopontine and laterodorsal tegmental nuclei [32] .…”

Section: Discussionmentioning

confidence: 99%

Core and Suggestive Symptoms of Dementia with Lewy Bodies Cluster in Persons with Mild Dementia

Rongve

Brønnick

Ballard

et al. 2010

Dement Geriatr Cogn Disord

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Objectives: To explore how the core and suggestive symptoms of dementia with Lewy bodies (DLB) cluster in persons with newly diagnosed mild dementia, and whether they are associated with a particular pattern of cognitive impairment. Method: Persons with mild dementia (n = 139) were recruited from dementia clinics in western Norway. Symptoms were rated using standardized instruments. A 2-step cluster analysis was applied to classify persons into groups according to scores on scales for hallucinations, parkinsonism, fluctuations and REM sleep behaviour disorder (RBD). Result: Four distinct clusters were revealed: a ‘Lewy body dementia’ (LBD) cluster with high scores for hallucinations, parkinsonism and fluctuation, and a ‘non-LBD’ cluster with low scores on all DLB symptom scales. In addition, 2 clusters with high scores on either RBD or cognitive fluctuation scales emerged. Persons in the LBD cluster had lower scores for visuospatial cognitive abilities as compared to the non-LBD group (p = 0.002). Conclusion: Applying cluster analysis, we identified distinct subgroups in mild dementia based on symptoms such as hallucinations, parkinsonism and cognitive fluctuations. Our findings provide empirical support for diagnosing DLB. Visual hallucinations and motor parkinsonism might be the most distinguishing symptoms for DLB in mild dementia.

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Mesopontine cholinergic neuron involvement in Lewy body dementia and multiple system atrophy

Abstract: Loss of cholinergic pedunculopontine tegmental nuclei/laterodorsal tegmental nuclei neurons occurs in both dementia with Lewy bodies and multiple system atrophy but is probably not the primary mechanism of REM sleep behavior disorder in these disorders.

Cited by 107 publications

References 22 publications

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies

Core and Suggestive Symptoms of Dementia with Lewy Bodies Cluster in Persons with Mild Dementia

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