Synergy effects of HbA1c and variants of APOE and BDNFVal66Met explains individual differences in memory performance

• Genetic variability act in synergy with HbA1c in shaping patterns of cognitive aging.
• Episodic memory was affected by such agents, whereas semantic memory was spared.
• BDNF66Met carriers with higher HbA1c levels evidenced slope decline in episodic recall.
• Longitudinal effects of BDNF × APOE × HbA1c and BDNF × APOE × age on episodic memory were found.

We aimed at exploring if synergy effects of Brain-Derived Neurotrophic Factor (BDNF) Val66Met, Apolipoprotein E (APOE) and HbA1c (glycated haemoglobin) could explain individual differences in memory performance over 10 years in a population based sample of nondemented adults (N = 888, 35–85 years at baseline). Episodic memory was affected by such agents, wheras semantic memory was spared. Both age and HbA1c were associated with episodic memory decline. BDNF66Met carriers with higher HbA1c levels evidenced slope decline in episodic recall. We found support for joint effects of BDNFVal66Met × APOE × HbA1c and BDNFVal66Met × APOE × age on rates of episodic memory change over ten years, after controlling for age, sex, education and cardiovascular diseases. We conclude that variants of genetic polymorphisms act in synergy with long-term blood glucose control in shaping patterns of cognitive aging.