Cognitive dispersion profiles and prediction of cognitive change in early-onset dementias: Results from LEADS

Introduction: Research into cognitive dispersion - a cognitive process score measuring the intra-individual variability (IIV) across a single testing session - suggests utility in neurodegenerative populations. Given widespread deficits observed in sporadic early-onset Alzheimer's disease (EOAD), however, it is unclear if examining cognitive dispersion shows benefit in this condition. Methods: A total of 309 participants (188 amyloid-positive EOAD, 43 amyloid-negative early-onset dementia [EOnonAD], 78 cognitively normal [CN]) completed neuropsychological testing twice over 12 months. Dispersion-related differences among groups were assessed, as was cognitive dispersion's capacity to predict domain-specific cognitive trajectories, and its convergence with imaging biomarkers. Results: EOAD participants displayed higher cognitive dispersion than EOnonAD participants, and associations with EOAD-specific biomarkers. Additionally, cognitive dispersion was associated with 12-month reliable change across several cognitive domains. Discussion: These preliminary results examine cognitive dispersion in sporadic EOAD. When used with baseline cognitive performance, cognitive dispersion measures may enrich future clinical trials in EOAD by enhancing treatment monitoring over time.