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Background: Bradyphrenia, best thought of as the mental equivalent of bradykinesia, has been described in several disorders of the brain including Parkinson's disease and schizophrenia; however, little is known about this phenomenon in Huntington's Disease (HD).
Objective: The aim of this study was to investigate the presence of bradyphrenia in HD using the Computerized Test of Information Processing (CTiP), an easy to administer and objective task that assesses cognitive processing speed with increasing task complexity.
Methods: This study included 211 participants: Huntington's Disease Integrated Staging System (HD-ISS) Stage 0 [n = 28], Stage 1 [n = 30], Stage 2 [n = 48] and Stage 3 [n = 48], and healthy controls (HC) [n = 57]. The CTiP incorporates three subtests: Simple Reaction Time (SRT), which assesses baseline motor function; Choice Reaction Time (CRT), with an added decisional component; and Semantic Search Reaction Time (SSRT), with an added conceptual component. SRT scores were subtracted from CRT and SSRT scores to establish a motor-corrected measure of central conduction time, which was used to operationalize bradyphrenia.
Results: HD-ISS and HC within-group reaction times differed significantly when comparing motor-corrected CRT vs SSRT (all s < 0.0001). Furthermore, the magnitude of these differences increased with HD disease stage (p < 0.0001). An ROC analysis determined that motor-corrected within-subject differences significantly distinguished Stage 2 + 3 from Stage 0 + 1 (AUC = 0.72, p < 0.0001).
Conclusions: We report evidence of bradyphrenia in HD that increases with disease progression. This processing deficit, which can be quantified using the CTiP, has the potential to greatly impact HD daily life and warrants additional research.
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http://dx.doi.org/10.1016/j.prdoa.2024.100243 | DOI Listing |
RSC Med Chem
August 2025
Department of Biological Science, Birla Institute of Technology and Science, Pilani Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District Telangana 500078 India
Mitochondrial dysfunction is one of the primary cellular conditions involved in developing Huntington's disease (HD) pathophysiology. The accumulation of mutant huntingtin protein with abnormal PolyQ repeats resulted in the death of striatal neurons with enhanced mitochondrial fragmentation. In search of neuroprotective molecules against HD conditions, we synthesized a set of isoxazole-based small molecules to screen their suitability as beneficial chemicals improving mitochondrial health.
View Article and Find Full Text PDFBrain Commun
August 2025
Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
was identified in human and mouse Huntington's disease brain as the pathogenic exon 1 mRNA generated from aberrant splicing between exon 1 and 2 of that contributes to aggregate formation and neuronal dysfunction. Detection of the huntingtin exon 1 protein (HTT1a) has been accomplished with Meso Scale Discovery, Homogeneous Time Resolved Fluorescence and immunoprecipitation assays in Huntington's disease knock-in mice, but direct detection in homogenates by gel electrophoresis and western blot assay has been lacking. Subcellular fractions prepared from mouse and human Huntington's disease brain were separated by gel electrophoresis and probed by western blot with neoepitope monoclonal antibodies 1B12 and 11G2 directed to the C-terminal eight residues of HTT1a.
View Article and Find Full Text PDFCell Biochem Biophys
September 2025
Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi, India.
Aging Cell
September 2025
Department of Cell Systems & Anatomy, University of Texas Health San Antonio, San Antonio, Texas, USA.
The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice.
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