Cognitive Reserve, Brain Reserve, APOE epsilon 4, and Cognition in Individuals with Subjective Cognitive Decline in the SILCODE Study

Background: Cognitive reserve (CR) and brain reserve (BR) could offer protective effects on cognition in the early stage of Alzheimer's disease (AD). However, the effects of CR or BR on cognition in individuals with subjective cognitive decline (SCD) are not clear. Objective: To explore the effects of CR and BR on cognition in subjects with SCD. Methods: We included 149 subjects from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Education was used as a proxy for CR, and head circumference was used as a proxy for BR. Multiple linear regression models were conducted to examine the effects of CR and BR on cognitive scores. Furthermore, we assessed differences in effects between APOE epsilon 4 carriers with SCD (n = 35) and APOE epsilon 4 non-carriers with SCD (n = 114) and linear trends among 4 reserve levels (low BR/CR, high BR/low CR, low BR/high CR, and high BR/high CR). Results: Both CR and BR had independent positive effects on multiple cognitive measures in SCD participants, and the effects of CR were greater than those of BR. CR has positive effects on cognitive measures in both APOE epsilon 4 carriers and non-carriers with SCD. However, the positive effects of BR on cognitive measures were observed in APOE epsilon 4 non-carriers with SCD but not in APOE epsilon 4 carriers with SCD. Furthermore, there was a linear trend toward better cognitive performance on all cognitive measures in the BR+/CR+ group, followed by the BR-/CR+, BR+/CR-, and BR-/CR- groups. Conclusion: This study suggests that both CR and BR have the potential to delay or slow cognitive decline in individuals with SCD