The NFL estimates that nearly three in 10 former players will develop debilitating brain conditions and that they will be stricken earlier and at least twice as often as the general population.
The disclosure Friday comes in separate actuarial data the league and players' lawyers released as part of their proposed $US765 million ($A827 million) settlement of thousands of concussion lawsuits.
Both the league and lead players' lawyers expect 28 per cent of the men will develop Alzheimer's disease or at least moderate dementia.
There are more than 19,000 living former players, meaning nearly 6,000 of them will fall into those two groups. Dozens more will be diagnosed with Lou Gehrig's or Parkinson's disease during their lives, according to the data.
The reports were prepared for Senior US District Judge Anita B. Brody, who is presiding over the class-action lawsuit in Philadelphia that accuses the NFL of hiding information that linked concussions to brain injuries.
The NFL report said the ex-players' diagnosis rates would be "materially higher than those expected in the general population" and would come at "notably younger ages."
The proposed settlement includes $US675 million for player awards, $US75 million for baseline assessments, $US10 million for research and $US5 million for public notice. It wouldn't cover current players.
Both sides have insisted that $US675 million would be enough to cover awards for 21,000 former players, given fund earnings estimated at 4.5 per cent annually. Brody initially had concerns the money might run out, while critics complained the NFL's offering is a pittance given its $US10 billion ($A10.8 billion) in annual revenues.
The NFL, in its report, said its estimates were "reasonable and conservative," and erred on the side of "overstating the number of players who will develop (illnesses)" to ensure the fund would be sufficient.
Lawyers for some players have complained that the negotiations have been cloaked in secrecy, leaving them unsure of whether their clients should participate or opt out by next month's deadline.
"We have zippo understanding," lawyer Thomas A. Demetrio, who represents the family of Dave Duerson, wrote in a motion Thursday. Duerson, the popular Chicago Bears safety, committed suicide in 2011.
The family of former linebacker Junior Seau, who also committed suicide, has announced plans to opt out. He and Duerson are among about 60 former players diagnosed after their deaths with the brain decay known as chronic traumatic encephalopathy. Known as CTE, it can only be diagnosed after death.
Friday's release of the actuarial data is designed to address some of the complaints.
About 28 per cent of all retired players are expected to be diagnosed with a neurocognitive injury that is eligible for compensation under the plan. But only 60 per cent of them are expected to seek awards, based on prior class-action litigation.
The 21,000 class members include 19,400 living men and the estates of 1,700 others.
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