Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(2), P. 115 - 128

Published: Dec. 14, 2021

Language: Английский

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Neurobiology of depression in Parkinson’s disease: Insights into epidemiology, molecular mechanisms and treatment strategies

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 85, P. 101840 - 101840

Published: Jan. 2, 2023

Language: Английский

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The noradrenergic subtype of Parkinson disease: from animal models to clinical practice

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 333 - 345

Published: May 4, 2023

Language: Английский

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Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders

Movement Disorders, Journal Year: 2022, Volume and Issue: 37(8), P. 1663 - 1672

Published: May 16, 2022

Abstract Background Neurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging. Objectives This study aimed characterize spatial patterns pathological change PD PSP transdiagnostic relationship between signals symptoms. Methods Twenty‐five people idiopathic PD, 14 probable PSP‐Richardson's syndrome, 24 age‐matched healthy controls were recruited. Participants underwent clinical assessments high‐resolution (0.08 mm 3 ) T‐magnetization‐transfer measure integrity vivo. obtained using subregional mean contrast ratios significant clusters; we further correlated measures apathy cognition, mixed‐effect models voxelwise analyses. Results groups showed degeneration caudal subregion relative controls. Mixed‐effect revealed a interaction disease‐group apathy‐related correlations ( β = 0.46, SE [standard error] 0.17, F (1, 35) 7.46, P 0.01), driven by strong correlation −0.58, 0.21, t (35) −2.76, 0.009). Across groups, analyses indicated that lower was associated worse cognition higher scores. Conclusions The nonmotor highlights role for noradrenergic dysfunction across PSP, confirming potential therapeutic strategies address cognitive behavioral features neurodegenerative disease. © 2022 Authors. Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society

Language: Английский

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Associations among locus coeruleus catecholamines, tau pathology, and memory in aging

Neuropsychopharmacology, Journal Year: 2022, Volume and Issue: 47(5), P. 1106 - 1113

Published: Jan. 15, 2022

Language: Английский

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Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease

Movement Disorders, Journal Year: 2022, Volume and Issue: 37(3), P. 479 - 489

Published: Feb. 3, 2022

ABSTRACT Background Parkinson's disease (PD) causes a loss of neuromelanin‐positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated nonmotor dysfunction. Objectives We used “neuromelanin sensitive” magnetic resonance imaging (MRI) to localize structural disintegration LC and its association with dysfunction PD. Methods A total 42 patients PD 24 age‐matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI LC. The contrast‐to‐noise ratio MTw signal (CNR ) was as an index integrity. performed slicewise voxelwise analyses map spatial patterns disintegration, complemented by principal component analysis (PCA). also tested for correlations between regional CNR severity symptoms. Results Mean right reduced relative controls. Voxelwise showed that attenuation confined mid‐caudal linked left associated orthostatic drop systolic blood pressure, whereas caudal most portion correlated apathy ratings. PCA identified bilateral more weakly expressed patients. This characterized gradient along rostro‐caudal dorso‐ventral axes nucleus. individual expression score this reflected overall Conclusion spatially heterogeneous may determine specific symptoms such dysregulation or apathy. © 2022 Authors. Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Language: Английский

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Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(5), P. 2182 - 2196

Published: Jan. 15, 2023

Abstract The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction cortical lesions. Accumulating evidence supports role behavioral neuropsychiatric manifestations featured AD. Experimental studies even suggest that AD‐associated drives brain neuroinflammatory status contributes to progression, including exacerbation Given important pathophysiologic etiologic roles involve AD stages, there is an urgent need expand our understanding mechanisms underlying vulnerability more precisely detail clinical progression changes Here, Professional Interest Area International Society Advance Research Treatment highlights knowledge gaps about within provides recommendations priorities specific research, biomarker development, modeling, intervention. Highlights Neuromodulatory degenerate pathological stages. pathophysiology exacerbated by degeneration. symptoms dementia. Biomarkers integrity would be value‐creating dementia care. present strategic prospects disease‐modifying therapies.

Language: Английский

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Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies

Brain, Journal Year: 2023, Volume and Issue: 146(9), P. 3690 - 3704

Published: June 3, 2023

Cholinergic changes play a fundamental role in the natural history of dementia with Lewy bodies and body disease general. Despite important achievements field cholinergic research, significant challenges remain. We conducted study four main objectives: (i) to examine integrity terminals newly diagnosed bodies; (ii) disentangle contribution by comparing patients without dementia; (iii) investigate vivo relationship between terminal loss atrophy cell clusters basal forebrain at different stages disease; (iv) test whether any asymmetrical degeneration would correlate motor dysfunction hypometabolism. To achieve these objectives, we comparative cross-sectional 25 (age 74 ± 5 years, 84% male), 15 healthy control subjects 75 6 67% male) Parkinson's 70 7 60% male). All participants underwent 18F-fluoroetoxybenzovesamicol PET high-resolution structural MRI. In addition, collected clinical 18F-fluorodeoxyglucose images. Brain images were normalized standard space regional tracer uptake volumetric indices extracted. Patients showed spatially distinct reductions across cerebral cortex, limbic system, thalamus brainstem. Also, binding cortical regions correlated quantitatively forebrain. contrast, decreased cortex despite preserved volumes. dementia, most severe least occipital compared those dementia. Interhemispheric asymmetry brain metabolism lateralized function. conclusion, this provides robust evidence for bodies, which correlates imaging measures degeneration. our findings suggest that function occurs 'before' neuronal Moreover, supports system is may be linked other transmitter systems. Our have implications understanding how pathology contributes features disease, progression patterns.

Language: Английский

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Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes

Brain, Journal Year: 2024, Volume and Issue: 147(7), P. 2308 - 2324

Published: Feb. 29, 2024

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's dementia with bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations the CNS of these disorders. More recently, studies have revealed denervation organs that receive parasympathetic denervation. This enables a comprehensive review changes encompassing both central peripheral regions, various disease stages diagnostic categories. Across studies, brain regions affected show equal or greater levels impairment compared to without dementia. observation suggests continuum between Patients exhibit relative sparing limbic whereas occipital superior temporal appear be similar extent patients implies posterior cell groups basal forebrain are early disorders, while more anterior typically later progression. The topographical observed by comorbid Alzheimer pathology may reflect combination seen pure forms those Alzheimer's disease. co-pathology important understand Thalamic innervation dementia, this contribute distinct clinical presentations groups. In thalamus variably affected, suggesting different sequential involvement disorder demonstrate abdominal from dorsal motor nucleus vagus, who experienced their prodrome. for understanding prodromal manifest phases conclusion, carry implications phenotypes influence co-pathology, delineating subtypes pathological spreading routes, developing tailored treatments targeting system.

Language: Английский

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Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 9, 2024

Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s (PD). Diffusion magnetic resonance imaging (MRI) has potential evaluate integrity LC system. The aim current study was determine whether diffusion MRI-measured its tracts are sensitive degeneration AD PD. Methods Post-mortem situ T1-weighted multi-shell MRI performed for 9 AD, 14 PD, 8 control brain donors. Fractional anisotropy (FA) mean diffusivity were derived from LC, between anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), primary motor (M1) or hippocampus. Brain tissue sections cortical regions obtained immunostained dopamine-beta hydroxylase (DBH) quantify cell density fiber load. Group comparisons correlations outcome measures using linear regression partial correlations. Results PD cases showed loss cells fibers. In increased DBH + immunoreactivity DLPFC compared controls, while reduced M1 controls. Higher FA within found which correlated with fibers LC. Increased LC-DLPFC tract combined group, whereas LC-M1 neuronal group. alterations not immunoreactivity. Conclusions MRI-detected associated local rather than changes cortex.

Language: Английский

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