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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Structural and molecular cholinergic imaging markers of cognitive decline in Parkinson’s disease

Brain, Journal Year: 2023, Volume and Issue: 146(12), P. 4964 - 4973

Published: July 4, 2023

Cognitive decline in Parkinson's disease is related to cholinergic system degeneration, which can be assessed vivo using structural MRI markers of basal forebrain volume and PET measures cortical activity. In the present study we aimed examine interrelation between degeneration PET-measured depletion acetylcholinesterase activity as well their relative contribution cognitive impairment disease. This cross-sectional included 143 participants without dementia 52 healthy control who underwent MRI, scanning with 11C-methyl-4-piperidinyl propionate (PMP) a measure activity, detailed assessment. Based on fifth percentile overall PMP signal from group, people were subdivided into normo-cholinergic (n = 94) hypo-cholinergic group 49). Volumes functionally defined posterior anterior subregions extracted an established automated volumetry approach based stereotactic atlas nuclei. We used Bayesian t-tests compare volumes controls, normo- after covarying out age, sex years education. Associations two imaging across all correlations respective relations performance different domains ANCOVAs. As specificity analysis, hippocampal was added analysis. found evidence for reduction compared both [Bayes factor against null model (BF10) 8.2] (BF10 6.0), while inconclusive < 3). continuous association analyses, significantly associated temporo-posterior distribution. The combined models prediction scores showed that (posterior signal) independently multi-domain deficits, more important predictors scores, including memory than volume. conclude accompanied by functional changes are deficits dementia. Comparatively, atrophy only seems have minimal involvement development early

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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Synthesis of new sulfonamide derivatives: Investigation of their interactions with carbonic anhydrase and cholinesterase enzymes by in vitro and in silico evaluations

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1314, P. 138798 - 138798

Published: May 30, 2024

Language: Английский

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Multisensory mechanisms of gait and balance in Parkinson’s disease: an integrative review

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(1), P. 82 - 92

Published: March 1, 2024

Understanding the neural underpinning of human gait and balance is one most pertinent challenges for 21st-century translational neuroscience due to profound impact that falls mobility disturbances have on our aging population. Posture control does not happen automatically, as previously believed, but rather requires continuous involvement central nervous mechanisms. To effectively exert over body, brain must integrate multiple streams sensory information, including visual, vestibular, somatosensory signals. The mechanisms which underpin integration these multisensory signals are principal topic present work. Existing theories focus how failure cognitive processes thought be involved in leads older adults. Insufficient emphasis, however, has been placed specific contributions individual modalities cross-modal interactions occur between relation balance. In work, we review somatosensory, vestibular modalities, along with their intersections adults patients Parkinson's disease. We also evidence temporal binding windows, shown highly fall risk Lastly, relate potential substrates, both at level neurobiology (concerning positron emission tomography imaging) electrophysiology electroencephalography). hope this integrative review, drawing influence across subdisciplines neuroscience, paves way novel research directions therapeutic neuromodulatory approaches, improve lives neurodegenerative diseases.

Language: Английский

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Subregion-specific associations of the basal forebrain with sleep and cognition in Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 20, 2025

To elucidate the role of basal forebrain (BF) in non-motor symptoms Parkinson's disease (PD), we investigated association sleep quality and cognition with BF volume functional connectivity. The gray matter anterior intermediate part (Ch4ai) lateral (Ch4al) nucleus basalis Meynert were negatively associated PSQI global score. posterior (Ch4p) was positively visuospatial, memory, executive functions. score correlated connectivity from Ch4al to cingulate, inferior parietal, temporal, medial prefrontal cortices, which correspond default mode network. Our results demonstrated that reduced portion Ch4 its aberrantly increased network closely related poor overall quality, while decreased cognitive function PD.

Language: Английский

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Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Background To date, cholinomimetics remain central in the pharmacotherapy of Alzheimer's disease (AD) dementia. However, postmortem investigations indicate that AD-typical progressive amnestic syndrome may also result from predominantly limbic non-AD neuropathology such as TDP-43 proteinopathy and argyrophilic grain disease. Experimental evidence links a beneficial response to early AD reduced markers cholinergic neurotransmission. impairment varies among patients with clinical presentation, likely due (co)-pathologies. Objective This study examines whether atrophy hypoperfusion can provide information about system clinically diagnosed AD. Methods Thirty-two mild cognitive or dementia underwent positron emission tomography (PET) tracer N-methyl-4-piperidyl-acetate (MP4A) estimate acetylcholinesterase (AChE) activity, neurological examinations, cerebral magnetic resonance imaging (MRI) neuropsychological assessment. The ‘cholinergic deficit’ was computed deviation AChE activity cognitively normal controls across cortex correlated gray matter (GM) perfusion temporo-parietal cortices typically affected by basal forebrain (BF) GM. Results Temporo-parietal GM, well inferior temporal medial ratio negatively deficit’. A smaller Ch4p area BF associated more significant deficit’, albeit lesser degree than cortical measures. Conclusions In AD, GM are closely volumes, making them possible for treatment neurodegeneration.

Language: Английский

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The involvement of the cholinergic system in Parkinson disease

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 215 - 229

Published: Jan. 1, 2025

Language: Английский

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