Cognitive reserve in young-onset cognitive impairment

Cognitive reserve (CR) reflects brain's resilience to pathology, enabling to maintain function despite structural damage. This study investigates its role in young-onset cognitive impairment (<65 years) beyond brain integrity and neurodegeneration. Participants underwent neuropsychological assessment - including the Cognitive Reserve Index questionnaire (CRIq) -, magnetic resonance imaging (MRI), and blood neurofilaments light-chain (NfLs) measurement. Scores of global cognition and domain-specific cognition were derived from Principal Component Analyses of neuropsychological results. Linear regression models estimated CR's contribution to global and domain-specific cognition, alongside age, sex, MRI measures, and NfLs as predictors. Among the 115 participants, global cognition was significantly explained by CR [effect size (ES) = 0.229], grey matter volume (ES = 0.348), and NfLs (ES = -0.302). The effect of CR was prominent on language and attentional-executive functions: while the CRIq subscore related to education predicted performance in both these domains, the subscore related to leisure activities was positively associated with the language domain only. These findings highlight CR's protective role in young-onset cognitive impairment, particularly for non-amnestic cognitive domains. Since a high CR can mask or compensate for neurological cognitive disorders delaying its diagnosis, our results suggest that measures of CR, including time spent on leisure activities, should be considered when interpreting neuropsychological tests.