LASSI-L detects early cognitive changes in pre-motor manifest Huntington's disease: a replication and validation...

Area of Science:

• Neuroscience
• Cognitive Psychology

Background:

• Cognitive decline, including executive function, processing speed, and memory deficits, is an early indicator in pre-motor Huntington's disease (preHD).
• The Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) was previously suggested to capture these early cognitive changes in preHD.

Purpose of the Study:

• To replicate and validate the LASSI-L's utility in detecting cognitive decline in preHD using larger datasets.
• To further analyze the LASSI-L's performance and compare it with established cognitive assessments.

Main Methods:

• Administered LASSI-L to 50 participants (25 preHD, 25 controls) and compared performance with MMSE, Trail A & B, SCWT, SDMT, Semantic Fluency, and CVLT-II.
• Investigated receiver operating curve (ROC) and practice effects over a 12-month interval.
• Compared performance in a preHD subgroup predicted to be far from diagnosis (Far subgroup) based on CAPs score and assessed construct validity via correlations with subcortical atrophy measures.

Main Results:

• PreHD participants showed significant differences on all LASSI-L sections compared to controls.
• The proactive semantic interference (PSI) section demonstrated high sensitivity (d=1.548), reliability (rho=0.88), and an excellent area under the ROC curve (AUROC=0.855).
• In the preHD Far subgroup, PSI was the only cognitive assessment to remain significant after FDR correction (p=0.03), and intrusions on PSI correlated negatively with caudate volume.

Conclusions:

• The LASSI-L is a sensitive, reliable, and efficient tool for identifying cognitive decline in preHD.
• The LASSI-L's unique paradigm, targeting multiple cognitive domains, surpasses many established tests in detecting early impairment.
• Further longitudinal validation could establish the LASSI-L as a valuable biomarker for preHD clinical research.