Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals.
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http://dx.doi.org/10.1002/mds.24041 | DOI Listing |
ACS Nano
January 2025
Nanomedicine Center, The Great Bay Area National Institute for Nanotechnology Innovation, 136 Kaiyuan Avenue, Guangzhou 510700, China.
The neurological implications of micro- and nanoplastic exposure have recently come under scrutiny due to the environmental prevalence of these synthetic materials. Parkinson's disease (PD) is a major neurological disorder clinically characterized by intracellular Lewy-body inclusions and dopaminergic neuronal death. These pathological hallmarks of PD, according to Braak's hypothesis, are mediated by the afferent propagation of α synuclein (αS) via the enteric nervous system, or the so-called gut-brain axis.
View Article and Find Full Text PDFJ Tissue Eng
January 2025
Developmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Growing evidence indicates that type 2 diabetes (T2D) is associated with an increased risk of developing Parkinson's disease (PD) through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentration, promoting insulin resistance, or to more physiological insulin concentration restoring insulin signalling function.
View Article and Find Full Text PDFRSC Med Chem
December 2024
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Sector 67, S. A. S. Nagar Punjab 160062 India
Aberrant protein misfolding and accumulation is considered to be a major pathological pillar of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Aggregation of amyloid-β (Aβ) peptide leads to the formation of toxic amyloid fibrils and is associated with cognitive dysfunction and memory loss in Alzheimer's disease (AD). Designing molecules that inhibit amyloid aggregation seems to be a rational approach to AD drug development.
View Article and Find Full Text PDFBrain Commun
January 2025
Department of Neurological Surgery, University of Louisville, Louisville, KY 40202, USA.
The subthalamic nucleus is thought to play a crucial role in controlling impulsive actions. Networked among the basal ganglia and receiving input from several cortical areas, the subthalamic nucleus is well positioned to influence action selection when faced with competing and conflicting action outcomes. The purpose of this study was to test the dissociable roles of the dorsal and ventral aspects of the subthalamic nucleus during action conflict in patients with Parkinson's disease undergoing intraoperative neurophysiological recording and to explore a potential mechanism for this inhibitory control.
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