The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, with well-researched effects on hippocampal structure and function throughout the lifespan. While its impact on episodic memory is well documented, its influence on implicit motor memory—a form of procedural memory also involving the hippocampus—remains poorly understood. Despite being largely preserved in ageing and Alzheimer’s disease, subtle procedural memory deficits may emerge and affect autonomy and quality of life.
To investigate the early effects of APOE-ε4 on implicit motor learning, we analysed behavioural and fMRI data from 54 healthy young adults (26 APOE-ε4 carriers, i.e Risk group, 28 non-carriers, i.e. Control group) performing the Serial Reaction Time Task across two visits. The Serial Reaction Time Task included blocks of random trials and repeated sequences, with participants unaware of the embedded patterns. This task was performed in a broader study on physical exercise; therefore, individual fitness levels constitute an additional factor of interest in this study. Sequence-specific performance was then isolated by contrasting sequence and random blocks.
Behaviourally, no main group effect was observed, indicating similar performance across groups. However, a significant genotype-by-visit interaction emerged: The Risk group showed improved performance from Visit 1 to Visit 2, whereas no such improvement was observed in the Control group. fMRI analyses revealed greater hippocampal activation in the Risk group during sequence versus random blocks, however, the fMRI analyses did not reveal a visit-by-genotype interaction. To explain this complex pattern between behavioural interaction effect and fMRI main effect, we propose that the Risk group may rely more heavily on hippocampal resources to sustain performance—adopting a compensatory, maximization-seeking strategy leading to performance increase over time—while the Control group may use a more efficient, optimization-driven approach that does not need to be refined and remains constant over time.
Although exploratory, these findings highlight the importance of considering APOE genotype and lifestyle factors such as physical fitness when modelling the development and maintenance of implicit motor memory across the lifespan.
