PET Clinics, Journal Year: 2024, Volume and Issue: 20(1), P. 113 - 120
Published: Oct. 30, 2024
Language: Английский
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
Citations
15
Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(9), P. 526 - 540
Published: Aug. 6, 2024
Language: Английский
Citations
13
Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3325 - 3343
Published: July 11, 2024
Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body (LBD), occurring approximately half all cases. Evidence shows that LBD patients with AD copathology show an accelerated course, greater risk cognitive decline and overall poorer prognosis. However, LBD-AD cases may heterogeneous motor non-motor phenotypes higher dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize current understanding by discussing synergistic effects neuropathological changes their clinical relevance. Furthermore, provide extensive overview neuroimaging fluid biomarkers under assessment for use possible diagnostic prognostic values. can predicted vivo means CSF, MRI PET markers, whereas most promising technique to date identifying different biological tissues α-synuclein seed amplification assay. Pathological imaging CSF are associated likelihood but do always mirror severity as pure AD. Implementing blood-based might allow faster screening copathology, thus improving sensitivity LBD-AD. Finally, discuss literature on novel candidate being exploited investigate other aspects neurodegeneration, such neuroaxonal injury, glial activation synaptic dysfunction. The thorough characterization should taken into account when considering differential diagnoses syndromes, evaluation individual level, guide symptomatic disease-modifying therapies.
Language: Английский
Citations
11
Nature Aging, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 20, 2025
Language: Английский
Citations
1
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
Citations
5
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
Citations
5
Annals of Neurology, Journal Year: 2025, Volume and Issue: unknown
Published: April 16, 2025
Objective The phenotype of patients with Parkinson's disease carrying GBA 1 variants (GBA‐PD) suggest similarities to symptomatology associated early cholinergic system degeneration. Therefore, this study aims investigate the clinical features and innervation pattern in GBA‐PD versus those without GBA1 mutation (non‐GBA‐PD). Methods A total 46 104 non‐GBA‐PD subjects were included. Clinical assessments included motor non‐motor evaluation, as well a comprehensive neuropsychological examination. Cholinergic integrity was assessed using 8 F‐Fluoroethoxybenzovesamicol ( 18 F‐FEOBV) positron emission tomography (PET) differences between non‐GBA‐PD. Given higher prevalence females GBA‐PD, analyses repeated when stratified by sex. Additionally, we examined association cognitive domains whole‐brain binding both groups. Exploratory F‐FEOBV among variants. Results exhibited burden symptoms lower performance on executive functions attention. We observed more pronounced denervation compared non‐GBA‐PD, primarily anterior, central, limbic regions. However, distribution loss its attention dysfunction comparable In addition, presentation differed significantly sexes. Interpretation These results an important role patients, which is related severe dysfunction. ANN NEUROL 2025
Language: Английский
Citations
0
Movement Disorders, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 3, 2024
Abstract Cognitive impairment is a well‐recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system thought to be key contributor. Both postmortem vivo positron emission tomography (PET) studies have provided valuable evidence changes PD, which are pronounced PD dementia (PDD). A growing body literature has employed magnetic resonance imaging (MRI), noninvasive, more cost‐effective alternative PET, examine structural PD. This review provides comprehensive discussion methodologies findings that focused on relationship between basal forebrain (cBF) integrity, based T1‐ diffusion‐weighted MRI, cognitive function Nucleus basalis Meynert (Ch4) volume been consistently reduced cognitively impaired samples shown potential utility as prognostic indicator for future decline. However, extent Ch4, especially early stages decline remains unclear. In addition, change anterior cBF regions not well established. underscores importance continued cross‐sectional longitudinal research elucidate role dysfunction manifestations © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.
Language: Английский
Citations
3
npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)
Published: June 29, 2024
Abstract In Parkinson’s disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential involvement of the cholinergic system. We investigated integrity in 149 asymptomatic GBA1 169 LRRK2 mutation carriers, 112 60 carriers PD, 492 idiopathic 180 controls from PPMI cohort. Basal forebrain volumes were extracted white matter pathways nucleus basalis Meynert (NBM) cortex pedunculopontine (PPN) thalamus assessed a free water-corrected DTI model. Bayesian ANCOVAs conducted for group comparisons linear mixed models assess associations cognitive decline. increased (Bayes Factor against null hypothesis (BF 10 ) = 75.2) 57.0) compared controls. LRRK2- GBA1-PD 14.5) PD 3.6*10 7 ), no difference between PD-GBA1 0.25). Mean diffusivity along medial NBM pathway was decreased 30.3). Over 5 years, declined across all domains whereas PD-LRRK2 patients only processing speed. found an interaction basal volume time predicting multiple PD-GBA1, but not PD-LRRK2. While mutations both at stages, this increase persists symptomatic stage slower decline these patients.
Language: Английский
Citations
2
Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9
Published: Sept. 27, 2024
Parkinson’s disease (PD) unfolds with pathological processes and neurodegeneration well before the emergence of noticeable motor symptoms, providing a window for early identification. The extended prodromal phase allows use risk stratification measures markers to pinpoint individuals likely develop PD. Importantly, growing body evidence emphasizes heterogeneity within clinically diagnosed comprises distinct subtypes exhibiting diverse clinical manifestations, pathophysiological mechanisms, patterns α-synuclein progression in central peripheral nervous systems. There is pressing need refine definition identification these subtypes. This requires comprehensive strategy that integrates genetic, pathological, imaging, multi-omics markers, alongside careful observation subtle non-motor symptoms. Such multi-dimensional classification PD will improve our understanding underlying pathophysiology, predictions endpoints, trajectory medication response, contribute drug discovery personalized medicine by identifying subtype-specific facilitate trials reducing confounding effects heterogeneity. Here we explore different subtyping methodologies PD, focusing on clinical, genetic molecular approaches. We also emphasize refined, theoretical priori models. These be prerequisite biological underpinnings subtypes, which have been defined large scale data-driven approaches fingerprints.
Language: Английский
Citations
2