Consolidation deficits in episodic memory define distinct clinical and neurodegenerative profiles in Huntington's disease
Por:
Martinez-Horta, S, Quevedo-García, A, Puig-Davi, A, Sampedro, F, Oltra-Cucarella, J, Pérez-Pérez, J, Franch-Martí, C, Olmedo-Saura, G, Rivas-Asensio, E, Vazquez-Oliver, A, Pérez-Carasol, L, Horta-Barba, A, Pagonabarraga, J, Kulisevsky, J
Publicada:
1 oct 2025
Ahead of Print:
1 oct 2025
Resumen:
Background: Huntington's disease (HD) is primarily associated with executive dysfunction, but episodic memory impairment is also present. Traditionally, these memory deficits have been attributed to retrieval difficulties linked to fronto-striatal dysfunction, rather than to disruptions in encoding or consolidation processes. However, the specific nature and diversity of memory impairments in HD remain underexplored. Objective: To characterize the profile of episodic memory impairment in HD, identify distinct cognitive phenotypes, and examine their clinical, neuroanatomical, and biomarker correlates. Methods: We assessed episodic memory in HD patients and healthy controls using the Free and Cued Selective Reminding Test (FCSRT), complemented by Item-Specific Deficit Approach (ISDA) indices to quantify encoding, consolidation, and retrieval deficits. Structural MRI was used to identify gray matter volume correlates, and plasma neurofilament light chain (NfL) was measured as a marker of neuroaxonal injury. Results: Compared to controls, HD patients showed marked impairments in free recall with preserved cued recall, suggesting predominant retrieval deficits. However, nearly one-third of patients exhibited global impairments across all FCSRT components, mainly driven by consolidation deficits consistent with medial temporal lobe dysfunction. This subgroup also showed worse cognitive and functional performance and significant atrophy in the hippocampus, entorhinal cortex, and parahippocampal gyrus. Conclusion: Episodic memory dysfunction in HD is heterogeneous and includes both retrieval-related and consolidation-driven profiles. These profiles reflect distinct neurodegenerative patterns, emphasizing the importance of cognitive subtyping for improving clinical characterization and biomarker development in HD.
Filiaciones:
Martinez-Horta, S:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Quevedo-García, A:
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Puig-Davi, A:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Sampedro, F:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Hosp Valle De Hebron, Inst Diagnost Imatge, Neuroradiol Dept, Barcelona, Spain
Oltra-Cucarella, J:
Univ Miguel Hernandez Elche, Dept Psicol Salud, Elche, Spain
Pérez-Pérez, J:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Franch-Martí, C:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Olmedo-Saura, G:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Rivas-Asensio, E:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Vazquez-Oliver, A:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Pérez-Carasol, L:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Horta-Barba, A:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Pagonabarraga, J:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Kulisevsky, J:
Hosp Santa Creu I Sant Pau, Neurol Dept, Movement Disorders Unit, Mas Casanovas 90, Barcelona 08041, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Autonomous Univ Barcelona, Dept Med, Barcelona, Spain
European Huntingtons Dis Network EHDN, Bellaterra, Spain
Green Submitted, gold
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