Non-motor asymmetry and dopamine degeneration in Parkinson’s disease DOI Creative Commons
Frederik Hansen, Karoline Knudsen, Malene Flensborg Damholdt

et al.

Brain Communications, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 24, 2024

Abstract Asymmetric dopaminergic degeneration of the striatum is a characteristic feature Parkinson’s disease, associated with right–left asymmetry in motor function. As such, studying provides insights into progressive neurodegeneration between cerebral hemispheres. Given impact Lewy pathology on various neurotransmitter systems beyond dopaminergic, it may be that other neuronal predominantly affected hemisphere are similarly affected. According to this hypothesis, would expected coincide systems. Consequently, functions primarily dependent integrity, such as function, should correlate bilateral non-motor rely systems, pupillary Therefore, study tested whether measures correlates striatal integrity. We also asymmetric greater overall. Using comparative cross-sectional design, we recruited newly diagnosed patients disease right-sided (n = 18), left-sided 15) or symmetric nigrostriatal denervation assessed dopamine PET. Detailed examinations lateralized function included lacrimation, hand skin wrinkling, salivation, olfaction and Healthy controls were for comparison. observed moderate-to-strong correlation putamen binding redilation speed [Spearman’s rank coefficient (rs) −0.53, 95% confidence interval (−0.77; −0.14), P 0.0084]. moderate correlations non-negative putaminal lacrimation [rs 0.35, (−0.00; 0.62), 0.0464] word recognition 0.36, (0.01; 0.63), 0.0410]. However, none significant after false discovery rate correction. group differences salivation (P 0.0390, ANOVA) trend towards participants loss compared healthy 0.0330, unadjusted). Additionally, showed greater, though non-significant, all those binding. In conclusion, contributes our understanding progression suggests link related autonomic particularly While findings do not support strict hemispheric association degeneration, potential relationships exist these features asymmetrical cholinergic.

Language: Английский

Parkinson’s Disease and Dementia with Lewy Bodies: One and the Same DOI Creative Commons
Per Borghammer, Niels Okkels, Daniel Weintraub

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(3), P. 383 - 397

Published: April 16, 2024

The question whether Parkinson’s disease dementia (PDD) and with Lewy bodies (DLB) are expressions of the same underlying has been vigorously debated for decades. recently proposed biological definitions body disease, which do not assign any particular importance to dopamine system over other degenerating neurotransmitter systems, once more brought discussion about different types forefront. Here, we briefly compare PDD DLB in terms their symptoms, imaging findings, neuropathology, ultimately finding them be indistinguishable. We then present a conceptual framework demonstrate how one can view clinical syndromes as manifestations shared disease. Early isolated RBD, pure autonomic failure perhaps even psychiatric represent diverse initial stages They characterized by heterogeneous comparatively limited neuronal dysfunction damage. In contrast, dementia, an encompassing term both DLB, represents uniform advanced stage Patients this category display extensive severe pathology, frequently accompanied co-existing pathologies, well multi-system degeneration. Thus, propose that should viewed single entity. Phenotypic variance is caused presence individual risk factors, mechanisms, co-pathologies. Distinct subtypes therefore defined subtype-specific mechanisms or biomarkers.

Language: Английский

Citations

17
Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes DOI
Niels Okkels, Michel J. Grothe, John‐Paul Taylor

et al.

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
Biological effects of pathologies in Lewy body diseases: why timing matters DOI
Elie Matar, Glenda M. Halliday

The Lancet Neurology, Journal Year: 2025, Volume and Issue: 24(5), P. 441 - 455

Published: April 16, 2025

Language: Английский

Citations

1
The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease DOI Creative Commons
Anders Björklund, Roger A. Barker

Brain, Journal Year: 2024, Volume and Issue: 147(6), P. 1937 - 1952

Published: Jan. 27, 2024

Abstract In recent years there has been a renewed interest in the basal forebrain cholinergic system as target for treatment of cognitive impairments patients with Parkinson’s disease, due part to need explore novel approaches treat symptoms disease and development more refined imaging tools that have made it possible monitor progressive changes structure function they evolve over time. parallel, emerging technologies allowing derivation authentic neurons from human pluripotent stem cells are providing new powerful exploration neuron replacement animal models disease-like decline. this review, we discuss rationale cell potential therapeutic strategy how approach can be explored rodent decline, building on insights gained extensive experimental work was performed primate 1980s 90s. Although therapies targeting so far focused mainly Alzheimer’s dementia may relevant condition. dementia, undergoes degeneration magnitude loss shown correlate level impairment. Thus, therapy aimed replace lost represents an interesting combat some major dementia.

Language: Английский

Citations

7
Dysfunction of motor cortices in Parkinson’s disease DOI Creative Commons
Hong‐Yuan Chu, Yoland Smith, William W. Lytton

et al.

Cerebral Cortex, Journal Year: 2024, Volume and Issue: 34(7)

Published: July 1, 2024

Abstract The cerebral cortex has long been thought to be involved in the pathophysiology of motor symptoms Parkinson’s disease. impaired cortical function is believed a direct and immediate effect pathologically patterned basal ganglia output, mediated by way ventral thalamus. However, recent studies humans with disease animal models have provided strong evidence suggesting that involvement much broader than merely serving as passive conduit for subcortical disturbances. In present review, we discuss disease–related changes frontal regions, focusing on neuropathology, plasticity, neurotransmission, altered network interactions. We will also examine exploring circuits potential targets neuromodulation treat

Language: Английский

Citations

7
Cholinergic innervation topography in GBA-associated de novo Parkinson’s disease patients DOI Creative Commons
Sofie Slingerland, Sygrid van der Zee, Giulia Carli

et al.

Brain, Journal Year: 2023, Volume and Issue: 147(3), P. 900 - 910

Published: Sept. 25, 2023

Abstract The most common genetic risk factors for Parkinson’s disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with mutations (GBA-PD) exhibit earlier age of onset and faster progression more severe cognitive impairments, postural instability gait problems. These GBA-PD features suggest cholinergic system pathologies. PET imaging vesicular acetylcholine transporter ligand 18F-F-fluoroethoxybenzovesamicol (18F-FEOBV PET) provides opportunity to investigate changes their relationship clinical in GBA-PD. study investigated 123 newly diagnosed, treatment-naïve subjects—with confirmed presynaptic dopaminergic deficits on imaging. Whole-gene sequencing saliva samples was performed evaluate variants. underwent extensive neuropsychological assessment all domains, motor evaluation Unified Disease Rating Scale, brain MRI, measure striatal-to-occipital ratios putamen 18F-FEOBV PET. We differences regional innervation between carriers non-GBA1 mutation (non-GBA-PD), using voxel-wise volume interest-based approaches. degree overlap t-maps from two-sample t-test models quantified Dice similarity coefficient. Seventeen (13.8%) subjects had a mutation. No significant were found non-GBA-PD at diagnosis. Lower binding both groups compared controls. (P < 0.05, cluster size 100) showed good (0.7326) maps. patients widespread reduction than when controls occipital, parietal, temporal frontal cortices FDR-corrected). In interest analyses (Bonferroni corrected), left parahippocampal gyrus affected De novo show distinct topography terminal binding. Although not distinguishable clinically, comparison healthy controls, denervation non-GBA-PD. A larger group is needed validate these findings. Our results that de differential patterns before phenotypic versus non-carrier observable.

Language: Английский

Citations

11
Cholinergic Denervation Patterns in Parkinson's Disease Associated With Cognitive Impairment Across Domains DOI Creative Commons
Emile d’Angremont, Remco J. Renken, Sygrid van der Zee

et al.

Human Brain Mapping, Journal Year: 2025, Volume and Issue: 46(2)

Published: Jan. 23, 2025

ABSTRACT Cognitive impairment is considered to be one of the key features Parkinson's disease (PD), ultimately resulting in PD‐related dementia approximately 80% patients over course disease. Several distinct cognitive syndromes PD have been suggested, driven by different neurotransmitter deficiencies and thus requiring treatment regimes. In this study, we aimed identify characteristic brain covariance patterns that reveal how cholinergic denervation related impairment, focusing on four domains, including attention, executive functioning, memory, visuospatial cognition. We applied scaled sub‐profile model principal component analysis cholinergic‐specific disease‐related cognition‐related using [ 18 F]fluoroethoxybenzovesamicol PET imaging. Stepwise logistic regression was predict state (PD vs. healthy control). Linear models were functioning within group, for each domain separately. assessed performance identified with leave‐one‐out cross validation performed bootstrapping assess pattern stability. included 34 various levels dysfunction 10 controls, similar age, sex, educational level. The strongly discriminative (AUC 0.91), most prominent posterior regions, lower tracer uptake compared controls. found largely overlapping across positive correlations between opercular cortex, left dorsolateral prefrontal cortex cingulate gyrus, among other executive, functioning. Cross showed significant predicted measured cognition scores, exception memory. a robust structural assessment PD, as well attentional, executive‐ patients.

Language: Английский

Citations

0
Validation of a data-driven motion-compensated PET brain image reconstruction algorithm in clinical patients using four radiotracers DOI Creative Commons
Ole Lajord Munk, Anders Rodell,

Patricia B. Danielsen

et al.

EJNMMI Physics, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 3, 2025

Language: Английский

Citations

0
Cholinergic degeneration and early cognitive signs in prodromal Lewy body dementia DOI Creative Commons
Kyung Ah Woo, Heejung Kim, Ryul Kim

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION Isolated REM sleep behavior disorder (iRBD) is a strong prodromal marker of Lewy body diseases (LBDs) – Parkinson's disease (PD) and dementia with bodies (DLB). Cholinergic loss linked to cognitive decline in these conditions, but its trajectory remains unclear. METHODS In cohort 92 iRBD participants baseline MRI, cholinergic basal forebrain (cBF) volume was measured, longitudinal changes analyzed 49 follow‐up scans. Cross‐sectional neuropsychological associations were examined across broader RBD–LBD continuum, including the plus 65 PD 15 DLB patients probable RBD. RESULTS cBF declined at comparable rates iRBD‐to‐PD iRBD‐to‐DLB converters, atrophy more severe phenoconversion. correlated attention, executive, memory deficits. iRBD, z ‐score < −1.0 predicted (hazard ratio = 9.57, p .009). CONCLUSION degeneration evolves from stage LBDs predicts dementia, highlighting window for cholinergic‐targeted intervention. Highlights Basal links executive function, RBD continuum. progresses similar DLB. At phenoconversion, greater than converters. strongly future iRBD. Executive dysfunction faster

Language: Английский

Citations

0
A Narrative Review on Biochemical Markers and Emerging Treatments in Prodromal Synucleinopathies DOI Creative Commons
Jamir Pitton Rissardo, Ana Letícia Fornari Caprara

Clinics and Practice, Journal Year: 2025, Volume and Issue: 15(3), P. 65 - 65

Published: March 17, 2025

Alpha-synuclein has been associated with neurodegeneration, especially in Parkinson’s disease (PD). This study aimed to review clinical, biochemical, and neuroimaging markers management of prodromal synucleinopathies. The state synucleinopathies can be better understood PD pathophysiology, it separated into premotor pre-diagnostic phases. incidence patients phase symptoms ranges from 0.07 14.30, the most frequently studied pathology is REM behavioral disorder (RBD). Neuroimaging are related dopamine denervation, brain perfusion changes, gross anatomy peripheral abnormalities. α-synuclein assays (SAA) CSF revealed high sensitivity (up 97%) specificity 92%); last decade, there was development other matrices (blood, skin, olfactory mucosa) for obtaining quantitative qualitative α-synuclein. Other biomarkers neurofilament light chain, DOPA decarboxylase, multiplexed mass spectrometry assay. Regarding genetic counseling α-synucleinopathies, an important topic clinical practice discuss high-risk individuals should involve basic principles autonomy, beneficence, non-maleficence. Some themes that reviewed involvement physical activity, diet (including alcohol, coffee, vitamin supplementation), smoking, sleep, stress pathophysiology number trials still scarce, studies evaluating intervention even lower.

Language: Английский

Citations

0