Cognitive reserve as a predictor of cognitive decline, but not age of diagnosis in patients with possible young-onset Alzheimer's disease: An underexplored population.

Background: The cognitive reserve (CR) theory aims to explain the disparity often observed between brain damage and its clinical manifestation. Objective: To explore the CR theory in young-onset Alzheimer's disease (YOAD), a population not previously investigated in this context. The goal is to assess whether, similar to late-onset Alzheimer's disease (LOAD), a high CR delays diagnosis but may accelerate cognitive decline. Methods: This is a retrospective study including 72 patients (ages: 46-64) who were diagnosed with possible YOAD. They were followed up for three years, using the Mini-Mental State Examination. Results: Unlike the findings with LOAD, age of diagnosis of the YOAD did not correlate significantly with CR variables, years of education or family size. However, years of education predicted greater cognitive decline in the first year, and women showed increased deterioration. Family size showed inconsistent associations, highlighting its limitations. Conclusions: In contrast to studies among LOAD, there was no significant correlation between age of diagnosis and CR among YOAD, suggesting that other mechanisms might be more influential than CR parameters in younger individuals. However, similar to LOAD, YOAD patients with higher education experienced faster disease progression, implying that diagnoses are frequently made when brain pathology is already severe. These findings reinforce the growing perspective that YOAD and LOAD may constitute distinct forms of AD, each with unique clinical and pathological features. They also underscore the urgent need for early detection tools and cognitive interventions to ease the challenges faced by these young patients.