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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Movement Disorders
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1494816
This article is part of the Research Topic From Genetic Discovery to Clinical Practice: Bridging the Gap in Huntington's Disease View all articles

Unraveling Progressive Verbal Memory Deficits in Huntington's Disease: Insights from the LASSI-L

Provisionally accepted
Luis A. Sierra Luis A. Sierra 1*Japleen Kaur Japleen Kaur 2Samuel Frank Samuel Frank 1,3Mark A Halko Mark A Halko 3,4Rosie E Curiel Rosie E Curiel 5David A Loewenstein David A Loewenstein 5Jody Corey-Bloom Jody Corey-Bloom 6Simon Laganiere Simon Laganiere 1,3
  • 1 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States
  • 2 University of California, San Diego, La Jolla, California, United States
  • 3 Harvard Medical School, Boston, Massachusetts, United States
  • 4 McLean Hospital, Belmont, Massachusetts, United States
  • 5 University of Miami, Coral Gables, Florida, United States
  • 6 UC San Diego Health, University of California, San Diego, San Diego, California, United States

The final, formatted version of the article will be published soon.

    Background and Objectives: Huntington'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.Methods: 151 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.Results: Sequential 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.The 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.

    Keywords: Semantic interference, Cognition, Huntington's disease, Executive Function, premotor manifest HD, LASSI-L

    Received: 11 Sep 2024; Accepted: 03 Jan 2025.

    Copyright: © 2025 Sierra, Kaur, Frank, Halko, Curiel, Loewenstein, Corey-Bloom and Laganiere. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luis A. Sierra, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.