Background: Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.

Aims: To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE ε4) allele.

Method: Participants were 22 SMC carrying the APOE ε4 allele (ε4+; mean age 72.18 years) and 58 SMC non-carriers (ε4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.

Results: ε4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.

Conclusions: The results provide the first evidence that ε4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.