Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L

Background and objectivesHuntington’s disease (HD) is characterized by progressive cognitive decline, with early deficits often preceding motor symptoms. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) captures many types of deficits in verbal memory including suscept...

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Main Authors: Luis A. Sierra, Japleen Kaur, Samuel A. Frank, Mark A. Halko, Rosie E. Curiel Cid, David A. Loewenstein, Jody Corey-Bloom, Simon Laganiere
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1494816/full
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author Luis A. Sierra
Japleen Kaur
Samuel A. Frank
Samuel A. Frank
Mark A. Halko
Mark A. Halko
Rosie E. Curiel Cid
David A. Loewenstein
Jody Corey-Bloom
Simon Laganiere
Simon Laganiere
author_facet Luis A. Sierra
Japleen Kaur
Samuel A. Frank
Samuel A. Frank
Mark A. Halko
Mark A. Halko
Rosie E. Curiel Cid
David A. Loewenstein
Jody Corey-Bloom
Simon Laganiere
Simon Laganiere
author_sort Luis A. Sierra
collection DOAJ
description Background and objectivesHuntington’s disease (HD) is characterized by progressive cognitive decline, with early deficits often preceding motor symptoms. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) captures many types of deficits in verbal memory including susceptibility to interference. The current study aims to delineate the progression of these deficits across different stages of HD.Methods151 participants (89 HD, 62 healthy controls) were recruited across three sites. HD participants were classified into three groups using a PIN score and TMS: >10 years from manifest HD, <10 years from manifest HD, and manifest HD. Group comparisons on the LASSI-L were assessed using multiple ANCOVAs adjusting for age, followed by post-hoc pairwise comparisons and a Bonferroni correction.ResultsSequential group differences for susceptibility to interference effects were observed on the LASSI-L. Proactive Semantic Interference (PSI) deficits emerged >10 years before manifest HD, Failure to Recover from PSI (frPSI) emerged <10 years before manifest HD, and in the Manifest HD stage, participants exhibited additional deficits in Retroactive Semantic Interference (RSI). Based on cutoff scores derived from healthy control performance, 98% (87/89) of the HD cohort demonstrated either normal performance or significant impairments, primarily in PSI, with some showing concurrent deficits in frPSI and/or RSI. Furthermore, 88% of participants adhered to the full sequential decline pattern, progressing from deficits in PSI, to frPSI, and then to RSI.DiscussionThe LASSI-L appears to be a useful tool for detecting early and progressive cognitive changes in Huntington’s disease, particularly by capturing the sequential nature of verbal memory deficits, including early vulnerability to interference. These findings suggest that the LASSI-L may help refine HD staging by integrating sequential neuropsychological markers of cognitive decline.
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spelling doaj-art-538a673f5915435bad2c338c9b1a02ce2025-08-20T03:12:53ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-02-011610.3389/fneur.2025.14948161494816Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-LLuis A. Sierra0Japleen Kaur1Samuel A. Frank2Samuel A. Frank3Mark A. Halko4Mark A. Halko5Rosie E. Curiel Cid6David A. Loewenstein7Jody Corey-Bloom8Simon Laganiere9Simon Laganiere10Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United StatesDepartment of Neurosciences, School of Medicine, University of California, San Diego, San Diego, CA, United StatesDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Psychiatry, McLean Hospital, Belmont, MA, United StatesCenter for Cognitive Neuroscience and Aging and Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, United StatesCenter for Cognitive Neuroscience and Aging and Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, United StatesDepartment of Neurosciences, School of Medicine, University of California, San Diego, San Diego, CA, United StatesDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesBackground and objectivesHuntington’s disease (HD) is characterized by progressive cognitive decline, with early deficits often preceding motor symptoms. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) captures many types of deficits in verbal memory including susceptibility to interference. The current study aims to delineate the progression of these deficits across different stages of HD.Methods151 participants (89 HD, 62 healthy controls) were recruited across three sites. HD participants were classified into three groups using a PIN score and TMS: >10 years from manifest HD, <10 years from manifest HD, and manifest HD. Group comparisons on the LASSI-L were assessed using multiple ANCOVAs adjusting for age, followed by post-hoc pairwise comparisons and a Bonferroni correction.ResultsSequential group differences for susceptibility to interference effects were observed on the LASSI-L. Proactive Semantic Interference (PSI) deficits emerged >10 years before manifest HD, Failure to Recover from PSI (frPSI) emerged <10 years before manifest HD, and in the Manifest HD stage, participants exhibited additional deficits in Retroactive Semantic Interference (RSI). Based on cutoff scores derived from healthy control performance, 98% (87/89) of the HD cohort demonstrated either normal performance or significant impairments, primarily in PSI, with some showing concurrent deficits in frPSI and/or RSI. Furthermore, 88% of participants adhered to the full sequential decline pattern, progressing from deficits in PSI, to frPSI, and then to RSI.DiscussionThe LASSI-L appears to be a useful tool for detecting early and progressive cognitive changes in Huntington’s disease, particularly by capturing the sequential nature of verbal memory deficits, including early vulnerability to interference. These findings suggest that the LASSI-L may help refine HD staging by integrating sequential neuropsychological markers of cognitive decline.https://www.frontiersin.org/articles/10.3389/fneur.2025.1494816/fullsemantic interferencecognitionHuntington’s diseaseexecutive functionpremotor manifest HDLASSI-L
spellingShingle Luis A. Sierra
Japleen Kaur
Samuel A. Frank
Samuel A. Frank
Mark A. Halko
Mark A. Halko
Rosie E. Curiel Cid
David A. Loewenstein
Jody Corey-Bloom
Simon Laganiere
Simon Laganiere
Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
Frontiers in Neurology
semantic interference
cognition
Huntington’s disease
executive function
premotor manifest HD
LASSI-L
title Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
title_full Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
title_fullStr Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
title_full_unstemmed Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
title_short Unraveling progressive verbal memory deficits in Huntington’s disease: insights from the LASSI-L
title_sort unraveling progressive verbal memory deficits in huntington s disease insights from the lassi l
topic semantic interference
cognition
Huntington’s disease
executive function
premotor manifest HD
LASSI-L
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1494816/full
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