Neuronal Loss and Α-Synuclein Pathology in the Superior Colliculus and Its Relationship to Visual Hallucinations in Dementia with Lewy Bodies

Erskine, Daniel; Thomas, Alan; Taylor, John‐Paul; Savage, Michael A.; Attems, Johannes; McKeith, Ian G.; Morris, Christopher M.; Khundakar, Ahmad

doi:10.1016/j.jagp.2017.01.005

Cited by 32 publications

(30 citation statements)

References 49 publications

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“…A subset of DLB cases (9/14) used for histological analysis had been subject to neuropsychological evaluation intra vitam. As detailed previously, these individuals had been assessed using the hallucinations subscale of the Neuropsychiatric Inventory (NPI) within 2 years prior to death . Comparison of the NPI hallucination score with neuropathological markers and GFAP demonstrated a significant positive correlation only between tau burden and NPI hallucination subscale score ( r s = 0.701, P = .035).…”

Section: Resultsmentioning

confidence: 99%

“…To quantify glial subpopulations and neuropathological lesions in the pulvinar in a separate cohort of cases and α‐synuclein pathology in the amygdala of the cases used for the transcriptomic study, images were taken on a Zeiss AxioVision Z.1 microscope using a DsFi1 camera (Nikon, Japan). As detailed previously, Stereologer software was used to delineate a region of interest with a 2.5 × objective, prior to the placement of disector frames in a uniform, random arrangement. This method prevented the introduction of bias by giving every area of the region of interest an equal probability of being sampled for analysis.…”

Section: Methodsmentioning

confidence: 99%

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Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

et al. 2018

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These results indicate that the pulvinar, a region with relatively low Lewy body pathological burden, manifests changes at the molecular level that differ from previous reports in a more severely affected region. We speculate that these alterations result from neurodegenerative changes in regions connected to the pulvinar and likely contribute to a variety of cognitive changes resulting from decreased cortical synchrony in dementia with Lewy bodies. © 2018 International Parkinson and Movement Disorder Society.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

et al. 2018

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“…The Braak hypothesis proposes that the main PD pathological process starts at the olfactory bulb and/or peripheral gastrointestinal nerve terminals, with secondary spread to the brainstem through the autonomic system . This prionlike phenomenon also targets the SC . The SC is a rich, complex, and widely connected entity, including a mutual inhibitory connection between each SC (Fig A) .…”

Section: Discussionmentioning

confidence: 99%

“…6 This prionlike phenomenon also targets the SC. 20 The SC is a rich, complex, and widely connected entity, including a mutual inhibitory connection between each SC ( Fig 4A). 21 Previous studies have found not only pathological α-synuclein accumulation in the human SC but also a more severe pathology in the SC layers connected to some midbrain structures, especially the dorsal raphe, the locus coeruleus, and the pedunculopontine nucleus (see Fig 4B).…”

Section: Discussionmentioning

confidence: 99%

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients

Moro

Bellot

Meoni

et al. 2020

Annals of Neurology

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Objective The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α‐synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. Methods De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. Results In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level–dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. Interpretation Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533–546

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“…Alternatively, a certain degree of neuronal integrity may be required for psychosis in Alzheimer's disease. A recent study of patients who had dementia with Lewy bodies found that the severity of hallucinations was positively correlated with neuronal density in the stratum griseum superficiale of the superior colliculus . This finding lends credulity to the notion that structure‐specific neurodegeneration can effect cessation of psychotic phenomena .…”

Section: Discussionmentioning

confidence: 80%

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers

Hinkle

Perepezko²,

Bakker

et al. 2017

Movement Disord Clin Pract

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Background Psychosis is among the most disabling complications of Parkinson’s disease (PD). The chronicity of PD psychosis remains understudied and the relative importance of dopaminergic therapy versus the disease process itself in engendering psychosis remains unclear. Objectives To examine pharmacologic and motoric correlates of PD psychosis onset and remission in a longitudinally monitored PD cohort. Methods We analyzed data from 165 participants enrolled in a longitudinal PD study through the Morris K. Udall Parkinson’s Disease Research Center of Excellence at Johns Hopkins University. Evaluations included formal psychiatric assessment and were conducted at two-year intervals. Regression with generalized estimated equations (GEE) was used to produce unadjusted and adjusted estimates for time-varying longitudinal associations between psychosis and putative risk factors. Results Sixty-two participants (37.6%) were diagnosed with psychosis during at least one evaluation. Of forty-nine participants with psychosis followed over multiple evaluations, 13 (26.5%) demonstrated remission despite significant Hoehn & Yahr stage increase (p=0.009); two of these cases later relapsed. Multivariable regression with GEE identified dementia diagnosis, akinesia-rigidity, anticholinergic usage, and levodopa-carbidopa dose to be significantly associated with psychosis, while disease duration was not. A sub-analysis of 30 incident psychosis cases suggested that dopamine agonist dose was lowered after psychosis onset with a compensatory increase in levodopa-carbidopa dosage. Conclusions Our findings suggest that in the context of standard therapy, PD-related psychotic disorder can remit at a frequency of approximately 27%. Additionally, akinetic-rigid motor impairment was more strongly associated with psychosis than disease duration, independent of cognitive impairment and medications.

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Neuronal Loss and Α-Synuclein Pathology in the Superior Colliculus and Its Relationship to Visual Hallucinations in Dementia with Lewy Bodies

Cited by 32 publications

References 49 publications

Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers

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