A major study released Tuesday that solidified the connections between football, repeated head trauma and chronic brain disease drew widespread response across the sport’s spectrum as former players, league officials and medical professionals continue to wrestle with the long-term effects of the game.

After the story first broke in major publications, the NFL acknowledged the issue of chronic traumatic encephalopathy, a degenerative brain condition. But the league — which opens its training camps this week — also said that many questions remain.

The study published by the American Medical Association examined the brains of deceased former football players (CTE can be diagnosed only after death) and found that 110 of 111 brains of those who played in the NFL had CTE.

CTE has been linked to repeated blows to the head.

Former center Randy Cross, 63, who spent his 13-year career with the 49ers, was asked about his initial reaction to the study’s findings.

“It makes it a little harder to defend football is kind of the first blush,” Cross said.

However, he quickly echoed Dr. Ann McKee, the lead author of the study, who acknowledged it had a “tremendous selection bias.” That is, of the brains of the 111 NFL players, many were donated by families because the players showed signs of CTE.

Cross estimates he sustained a minimum of 12 concussions a season during his career based on today’s standards, but he’s having no current issues from a “mental-acuity standpoint.” He also said that the “vast majority” of former players with whom he speaks are not struggling with brain trauma. Cross has agreed to donate his brain to the Concussion Legacy Foundation to provide better data and advance research.

“The study doesn’t have what you would call an ideal test sample,” Cross said. “It’s one of the reasons I’ve donated my brain. You can’t just study all the brains of guys that have some kind of problems, or a sad end, and the family decides to donate their brain. There should be no shock that there was some issue. The fact that it’s CTE — the bottom line is that until they figure out exactly what causes it, stuff like this doesn’t really advance the story.”

The NFL issued a statement saying such reports are important for advancing science related to head trauma, and said the league “will continue to work with a wide range of experts to improve the health of current and former NFL athletes.”

The journal update includes many previously reported cases, including former Raiders quarterback Ken Stabler and ex-NFL players Bubba Smith, Dave Duerson and Ralph Wenzel.

Research on 202 former NFL, college and even high school football players found evidence of a brain disease linked to repeated head blows in nearly all of them. The study doesn’t confirm that the condition is common in all football players; it reflects high occurrence in samples at a Boston brain bank that studies CTE.

“There are many questions that remain unanswered,” said McKee, a Boston University neuroscientist. “Obviously, this doesn’t represent the prevalence in the general population, but the fact that we’ve been able to gather this high a number of cases in such a short period of time says that this disease is not uncommon,” McKee told the Washington Post. “In fact, I think it’s much more common than we currently realize. And more importantly, this is a problem in football that we need to address, and we need to address now in order to bring some hope and optimism to football players.”

The NFL finally acknowledged a link between head blows and brain disease in 2015, and agreed in a $1 billion settlement to compensate former players who had accused the league of hiding the risks. No money has been paid yet.

“We appreciate the work done by Dr. McKee and her colleagues for the value it adds in the ongoing quest for a better understanding of CTE,” the league said in its statement. “As noted by the authors, there are still many unanswered questions relating to the cause, incidence and prevalence of long-term effects of head trauma such as CTE. “

Last year, the NFL pledged $100 million in support for independent medical research and engineering advancements in neuroscience-related topics.

McKee said research from the brain bank may lead to answers and an understanding of how to detect the disease in life, “while there’s still a chance to do something about it.” There’s no known treatment for CTE.

In the study, nearly 88 percent of all the brains (177) had CTE. Three of 14 who had played only in high school had CTE, as did 48 of 53 college players, 9 of 14 semiprofessional players, and 7 of 8 Canadian Football League players. CTE was not found in the brains of two who played football before high school.

A panel of neuropathologists made the diagnosis by examining brain tissue, using recent criteria from the National Institute of Neurological Disorders and Stroke, McKee said.

McKee and colleagues found the most severe disease in former professional players; mild disease was found in all three former high school players diagnosed with CTE.

The average age of death among all players studied was 66. There were 18 suicides among the 177 diagnosed.

Some researchers are experimenting with tests for CTE performed on the living.

On Tuesday, wide receiver Andrew Hawkins, 31, announced he was retiring from the NFL after six seasons and donating his brain to concussion research. Hawkins signed with the Patriots in May, but said his body wasn’t responding during the offseason.

Vic Tafur and Eric Branch are San Francisco Chronicle staff writers. Email: vtafur@sfchronicle.com, ebranch@sfchronicle.com Twitter: @VicTafur, @Eric_Branch

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