Shaping the cognitive reserve: the role of lifelong enrichment and education in the Alzheimer's disease continuum.

Background: Leisure activities (LAs) are recognized as major contributors to cognitive reserve (CR), potentially mitigating age-related cognitive decline and dementia progression. However, the specific associations between lifelong engagement in different types of LAs, education (as a proxy of CR), and cognitive functioning along the Alzheimer's disease (AD) continuum remain poorly defined. This study aimed to investigate the association between education and LAs in relation to current cognitive performance in healthy subjects (HS), individuals with subjective cognitive decline (SCD), amnestic mild cognitive impairment (a-MCI), and AD patients. Methods: Two hundred eighty-six participants (82 AD, 98 a-MCI, 39 SCD, 67 HS) underwent comprehensive neuropsychological testing and completed a validated questionnaire assessing the frequency of cognitive (C1-C8), social (S1-S5), and physical (P1-P5) activities during youth, middle, and late adulthood. Associations among education, LAs, and cognitive outcomes were analyzed using Spearman's correlations and moderation analyses, while between-group differences were explored with Kruskal-Wallis ANOVAs. Results: Education showed significant correlations with most LA domains across all groups. Distinct activity-cognition patterns emerged along the disease continuum. In HS, participation in individual sports during youth and midlife correlated with global cognitive efficiency and memory. In SCD individuals, pet care during midlife was associated with memory, whereas in a-MCI patients, attending lectures and sewing/knitting were related to current cognitive efficiency. No significant associations were observed in AD patients. Moderation analyses revealed that education was significantly associated with the relationship between LA engagement and cognitive outcomes in HS, SCD, and a-MCI, but not in AD. Kruskal-Wallis analyses indicated reduced engagement in cognitive and social activities across disease stages compared with HS, particularly during youth and midlife. Discussion: Differences in lifelong LA engagement were evident across diagnostic groups, and education was associated with variations in cognition-activity relationships. These findings suggest that the role of CR through leisure engagement may vary across disease stages. Conclusion: Education-related cognitive reserve was linked to the relationship between lifelong leisure activities and cognitive performance in healthy individuals and early-stage AD conditions, but not in advanced AD, highlighting the potential role of early-life cognitive, social, and physical enrichment in supporting preserved cognitive function.