Brain confirmed the news on his blog.
The move will see a restructure of the senior leadership in the region, with Bob Grove, currently president of the North Asia sub-region, taking the newly created role of APACMEA chief operating officer.
Rob Holdheim, currently CEO of South Asia, Middle East and Africa, will partner with global vice chairman Michael Stewart on developing an advisory offer for the firm, the company said in a statement. Meanwhile, Iain Twine, currently CEO of Southeast Asia & Australia, will lead the Reputation practice for the APACMEA region.
Brain, who leaves his role on 9 May, joined Edelman in January 2004 to run the Europe business from London, before taking charge of the Asia business from New Zealand and then moving to the expanded APACMEA role.
Explaining his decision to step down, Brain said: "Running Europe, then Asia and then Asia Pacific, Middle East & Africa are essentially three versions of the same job. Brilliant, challenging jobs, but fundamentally and structurally similar. And whilst my board role at the firm and various projects have leavened that recently with global tasks, it is difficult to sustain and drive those from islands in the middle of the South Pacific.
"And I don’t want to do the same thing for more years, wonderful though this firm is and much as I love the work and the people and am committed to the mission.
"Recently a good friend advised me that you have to dedicate time to finding and developing your ‘next thing’ and working full-time as a regional CEO is not allowing me to do that (quite rightly). And the timing is favourable as we are starting planning for our new financial year and we now have a deep and talented bench of people in the region, who will be led from here on by my good friend and colleague Bob Grove."
Brain added: "Leaving this firm will be hard emotionally, but the decision was a very easy one to take in the end. Sometimes you just know."
The European business doubled under Brain’s tenure, as did the Asia operation.
Trading has been more challenging in recent months, with the agency’s Dubai business Edelman Dabo laying off about 20 members of staff amid a slowdown in global growth at the company in 2016.
Before joining Edelman, Brain was joint CEO at Weber Shandwick in London. His other roles have included MD at Burson-Marsteller and PR manager at Visa in Southeast Asia.