As late as last year, he was diagnosed with a range of psychiatric illnesses, including dementia, major depressive disorder and post-traumatic stress disorder.
The illnesses were linked to the fact that he has spent 11 of the past 20 years in Pakistani prisons fighting charges of corruption. He claims to have been tortured during his incarceration.
In March 2007 New York psychiatrist Philip Saltiel found that Zardari's time in detention left him with severe "emotional instability", memory loss and concentration problems, according to court documents seen by the Financial Times.
Stephen Reich, a psychiatrist from New York State, said Zardari was unable to recall the birthdays of his wife and children and had thought about suicide.
"He had difficulty focusing, concentrating and paying attention, is persistently sad, chronically anxious and apprehensive. He stated that he has had suicidal thoughts, but has not made any suicide gestures," Reich wrote.
Reich re-examined Zardari in June and September last year, each time reporting that he had made progress but still had problems that might make it impossible for him to testify in court."I do not see any improvement in these issues for at least a year," he said.
Zardari used the medical reports to successfully fight a now defunct English High Court case in which the Pakistan government sought to sue him over alleged corruption. The case was dropped in March.
Now those very documents are coming back to haunt him.
Co-chair of the Pakistan People's Party, founded by his father-in-law Zulfiqar Ali Bhutto and led for long by his wife Benazir, 52-year-old Zardari is the party's candidate to succeed Pervez Musharraf as president.
Alluding to the fact that Pakistan is a nuclear weapon state, western commentators snidely wonder how sensible it would be to have a mentally unstable president as its CEO.
Embarrassed, Zardari's supporters are scurrying to reassure international community that he is in fine fettle now.
Wajid Shamsul Hasan, Pakistan's high commissioner to London and a close friend of the Bhuttos, told Financial Times that Zardari had had subsequent medical examinations and his doctors had "declared him medically fit to run for political office and free of any symptoms."
"You have got to understand that while he was in prison on charges that were never proven, there were attempts to kill him," Hasan said. "At that time, he was surrounded by fear all the time. Any human being living in such a condition will of course suffer from the effects of continuous fear. But that is all history.
"In fact, many people were very impressed to see Mr Zardari go through the trauma of the assassination of Benazir Bhutto, but still hold himself together, hold his family, especially his children, close to him at this very difficult time."
But Zardari's enemies could be trusted to latch on to the court documents and seek to frustrate his presidential ambitions.
"I don't know if someone's going to raise it or not, but being of sound mind is a condition of becoming president," said Shafqat Mahmood, a newspaper columnist. "His opponents may bring it up to attack Mr Zardari, and submit a petition to the Election Commission."