{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T18:21:56Z","timestamp":1794075716127,"version":"4.8.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>Cognitive decline is an important early sign in pre-motor manifest Huntington\u2019s disease (preHD) and is characterized by deficits across multiple domains including executive function, psychomotor processing speed, and memory retrieval. Prior work suggested that the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L)\u2013a verbal learning task that simultaneously targets these domains - could capture early cognitive changes in preHD. The current study aimed to replicate, validate and further analyze the LASSI-L in preHD using larger datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LASSI-L was administered to 50 participants (25 preHD and 25 Healthy Controls) matched for age, education, and sex in a longitudinal study of disease progression and compared to performance on MMSE, Trail A &amp;amp; B, SCWT, SDMT, Semantic Fluency (Animals), and CVLT-II. Performance was then compared to a separate age-education matched-cohort of 25 preHD participants. Receiver operating curve (ROC) and practice effects (12\u2009month interval) were investigated. Group comparisons were repeated using a preHD subgroup restricted to participants predicted to be far from diagnosis (Far subgroup), based on CAG-Age-Product scaled (CAPs) score. Construct validity was assessed through correlations with previously established measures of subcortical atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PreHD performance on all sections of the LASSI-L was significantly different from controls. The proactive semantic interference section (PSI) was sensitive (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001, <jats:italic>d<\/jats:italic>\u2009=\u20091.548), similar across preHD datasets (<jats:italic>p<\/jats:italic>\u2009=\u20091.0), reliable on test\u2013retest over 12\u2009months (spearman rho\u2009=\u20090.88; <jats:italic>p<\/jats:italic> =\u2009&amp;lt;0.00001) and associated with an excellent area under ROC (AUROC) of 0.855. In the preHD Far subgroup comparison, PSI was the only cognitive assessment to survive FDR\u2009&amp;lt;\u20090.05 (<jats:italic>p<\/jats:italic>\u2009=\u20090.03). The number of intrusions on PSI was negatively correlated with caudate volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The LASSI-L is a sensitive, reliable, efficient tool for detecting cognitive decline in preHD. By using a unique verbal learning test paradigm that simultaneously targets executive function, processing speed and memory retrieval, the LASSI-L outperforms many other established tests and captures early signs of cognitive impairment. With further longitudinal validation, the LASSI-L could prove to be a useful biomarker for clinical research in preHD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1191718","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T16:12:59Z","timestamp":1689696779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["LASSI-L detects early cognitive changes in pre-motor manifest Huntington\u2019s disease: a replication and validation study"],"prefix":"10.3389","volume":"14","author":[{"given":"Luis A.","family":"Sierra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby B.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementina J.","family":"Ullman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarbesh R.","family":"Pandeya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Halko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody","family":"Corey-Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Laganiere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1007\/s11910-011-0215-x","article-title":"Cognitive impairment in Huntington disease: diagnosis and treatment","volume":"11","author":"Paulsen","year":"2011","journal-title":"Curr Neurol Neurosci Rep"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1111\/j.1468-1331.2007.01975.x","article-title":"Cognitive changes in asymptomatic carriers of the Huntington disease mutation 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