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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 ε 4) allele., Method: Participants were 22 SMC carrying the APOE ε 4 allele ( ε 4+; mean age 72.18 years) and 58 SMC non-carriers ( ε 4-; 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: ε 4+ 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 ε 4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity., Declaration of Interest: D.A. has served on scientific advisory boards for Novartis, Eli Lilly, Janssen, Prana and Pfizer, and as Editor-in-Chief for International Psychogeriatrics; received speaker honoraria from Pfizer and Lundbeck, and research support from Eli Lilly, GlaxoSmithKline, Forest Laboratories, Novartis, and CSIRO. C.L.M. has received consulting fees from Eli Lilly and Prana Biotechnology, and has stock ownership in Prana Biotechnology. C.C.R. has received consultancy payments from Roche and Piramal, and research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Piramal and Navidea for amyloid imaging. C.S. has provided clinical consultancy and been on scientific advisory committees for the Australian CSIRO, Alzheimer's Australia, University of Melbourne and other relationships, which are subject to confidentiality clauses; she has been a named Chief Investigator on investigator-driven collaborative research projects in partnership with Pfizer, Merck, Piramal, Bayer and GE Healthcare. Her research programme has received support from the National Health and Medical Research Council Alzheimer's Association, Collier Trust, Scobie and Claire McKinnon Foundation, JO and JR Wicking Trust, Shepherd Foundation, Brain Foundation, Mason Foundation, Ramaciotti Foundation, Alzheimer's Australia and the Royal Australian College of Physicians., Copyright and Usage: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.