Parkinson disease psychosis: from phenomenology to neurobiological mechanisms

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(3), P. 135 - 150

Published: Jan. 15, 2024

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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The 2022 yearbook of Neurorestoratology

Journal of Neurorestoratology, Journal Year: 2023, Volume and Issue: 11(2), P. 100054 - 100054

Published: April 27, 2023

There was much progress in the field of Neurorestoratology year 2022. It included highlighting advances understanding pathogenesis neurological diseases, neurorestorative mechanisms, and clinical treatments as compiled 2022 yearbook Neurorestoratology. is still controversy about whether amyloid β-protein tau protein deposition are reasons for or results Alzheimer's disease (AD) pathology. The fabricated images important key articles that speculated on AD were found. Cholinergic deficiency decrease loss strength glutamatergic synapse, limited failing bidirectional cholinergic upregulation early cognitive impairment, progressive posterior-to-anterior cortical denervation could result appearance AD. Exploration mechanisms found more detail ways neuromodulation, immunomodulation, neurogenesis, neural network circuitry reconstruction, neuroprotection, nervous structural repair, neuroplasticity. Several kinds cell therapies diseases showed effects open-label and/or non-randomized studies trials. However, mesenchymal stromal cells mononuclear did not demonstrate improve quality life patients with neurodegenerative neurotrauma including stroke, spinal cord injury (SCI), amyotrophic lateral sclerosis randomized, double-blind, placebo-controlled trials (RDPCTs). Clinical through neurostimulation/neuromodulation brain–computer/machine interface yielded positive AD, Parkinson's disease, SCI, cerebral palsy, other RDPCTs. Neurorestorative surgery, pharmaceutical therapy interventions have demonstrated various considered incurable Thus, this year, additional guidelines, assessment scales, standards set up revised. These guidelines brain trauma (2022 China version), neurorestoration (IANR/CANR 2022), SCI dysfunction rating scale (SCIDQLRS) (IANR version). varying therapeutic strategies higher evidence-based medicine now benefiting currently diseases. Hopefully some them may become routine these near future.

Language: Английский

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Basal forebrain integrity, cholinergic innervation and cognition in idiopathic Parkinson’s disease

Brain, Journal Year: 2023, Volume and Issue: 147(5), P. 1799 - 1808

Published: Dec. 18, 2023

Most individuals with Parkinson's disease experience cognitive decline. Mounting evidence suggests this is partially caused by cholinergic denervation due to α-synuclein pathology in the basal forebrain. Alpha-synuclein deposition causes inflammation, which can be measured free water fraction, a diffusion MRI-derived metric of extracellular water. Prior studies have shown an association between forebrain integrity and cognition, levels volume acetylcholine, but no study has directly investigated whether physiology mediates relationship acetylcholine cognition disease. We these variables cross-sectional analysis 101 Cholinergic were using fluorine-18 fluoroethoxybenzovesamicol (18F-FEOBV) PET imaging. innervation regions interest included medial, lateral capsular perisylvian hippocampus. Brain fraction quantified T1 MRI, respectively. Cognitive measures composites attention/working memory, executive function, immediate memory delayed memory. Data entered into parallel mediation analyses projection areas as predictors, mediators each domain outcomes. All controlled for age, years education, levodopa equivalency dose systolic blood pressure. The metrics fully mediated medial Basal fraction. For all mediations was significant, while not. hippocampal significant models, Free temporal These findings suggest that two reflect different stages neurodegenerative processes add additional forebrain, decline

Language: Английский

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Atrophy of the Cholinergic Basal Forebrain can Detect Presynaptic Cholinergic Loss in Parkinson's Disease

Annals of Neurology, Journal Year: 2023, Volume and Issue: 93(5), P. 991 - 998

Published: Jan. 4, 2023

Structural imaging of the cholinergic basal forebrain may provide a biomarker for system integrity that can be used in motor and non-motor outcome studies Parkinson's disease. However, no prior have validated these structural metrics with nerve terminal vivo Here, we correlate morphometry topography vesicular acetylcholine transporter large sample.

Language: Английский

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Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 26, 2023

Abstract Parkinson’s disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent receptor-mediated mechanisms contributing progression. Combining spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, detect a diverse set influencing gray matter atrophy, activity dysregulation, microstructural degeneration, dendrite transporter loss. Inter-individual variability in receptor correlates symptom severity along two distinct axes, representing motor psychomotor symptoms large GABAergic glutamatergic contributions, cholinergically-dominant visuospatial, psychiatric memory dysfunction. Our work demonstrates that architecture helps explain multi-factorial re-organization, suggests distinct, co-existing processes underlie disease.

Language: Английский

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Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson’s Disease

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(s2), P. S353 - S365

Published: Feb. 6, 2024

Assessing imaging biomarker in the prodromal and early phases of Parkinson’s disease (PD) is great importance to ensure an safe diagnosis. In last decades, modalities advanced are now able assess many different aspects neurodegeneration PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT with Ioflupane, more specific PET tracers degeneration dopaminergic system available. Furthermore, metabolic patterns be used anticipate a phenoconversion PD manifest this regard, it worth mentioning that inflammation will gain significance. Molecular neurotransmitters like serotonin, noradrenaline acetylcholine shed light on non-motor symptoms. Outside brain, molecular heart gut PD-related autonomous nervous system. Moreover, optical coherence tomography noninvasively detect retinal fibers as potential review, we describe these state-of-the-art point out how far techniques future pave way towards biomarker-based staging

Language: Английский

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Parkinson’s Disease: Biomarkers for Diagnosis and Disease Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12379 - 12379

Published: Nov. 18, 2024

Parkinson's disease (PD) is a progressive neurological that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis diagnosing disease, which can be mild in early stages overlap other disorders. As result, testing medical records mostly relied upon diagnosis, posing substantial challenges during initial diagnosis continuous monitoring. Recent biochemical, neuroimaging, genetic have helped us understand pathophysiology disease. This comprehensive study focuses on these biomarkers, were chosen based their relevance, methodological excellence, contribution field. Biochemical including α-synuclein glial fibrillary acidic protein (GFAP), predict severity progression. The dopaminergic system widely used as neuroimaging biomarker diagnose PD. Numerous genes genome wide association (GWAS) sites been related development research SNCA gene leucine-rich repeat kinase 2 (LRRK2) shown promising results. By evaluating current studies, this review intends uncover gaps validation use, while also highlighting improvements. It emphasizes need dependable reproducible indicators improving PD prognosis. These may open up new avenues progression tracking, personalized treatment programs.

Language: Английский

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Multimodal neuroimaging to characterize symptom-specific networks in movement disorders

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 14, 2024

Movement disorders, such as Parkinson's disease, essential tremor, and dystonia, are characterized by their predominant motor symptoms, yet diseases causing abnormal movement also encompass several other including non-motor symptoms. Here we review recent advances from studies of brain lesions, neuroimaging, neuromodulation that provide converging evidence on symptom-specific networks in disorders. Although disorders have traditionally been conceptualized the basal ganglia, cumulative data lesions parkinsonism, tremor dystonia now demonstrated this view is incomplete. Several shown a given disorder occur heterogeneous locations, but disrupt common networks, which appear to be specific each phenotype. In addition, findings structural functional neuroimaging abnormalities extend far beyond associated with fact, strongly influenced constellation patients' symptoms seem map rather than individual anatomical structures or single neurotransmitters. Finally, observations deep stimulation clinical changes, both symptom improvement side effects, dependent modulation large-scale instead purely local effects neuromodulation. Combined, multimodal suggests arise distinct encouraging imaging better characterize underlying mechanisms individually tailor treatment approaches.

Language: Английский

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