The question has puzzled doctors since the days Joe Louis ruled the heavyweight division.
Why do some fighters suffer brain damage from punches absorbed in the ring while others get hit in the head for years and show few effects?
A study that has applications outside of boxing could provide at least a partial answer, and researchers say their intent isn't to end contact sports, but to find ways to make them safer.
''You can't stop these sports, and the last thing we want to do is stop these sports,'' said Dr. Charles Bernick, the chief investigator for the project. ''But we want to be able to protect athletes from long-term brain issues.''
Almost 150 current boxers and mixed martial arts fighters have already taken their first set of tests for the study, funded mostly by Las Vegas hotel magnate Kirk Kerkorian and conducted at the Cleveland Clinic's new Lou Ruvo Center for Brain Health in downtown Las Vegas. Researchers hope to eventually enroll more than 600 fighters in what is hoped to be at least a four-year study of their brains.
The motive for most of the fighters is simple - they save $800 to $1,000 for a baseline MRI they would need anyway to get a Nevada state license to box or participate in professional MMA. For some, though, it is more about peace of mind than it is about the money.
''It's my profession and I want to pursue a long, healthy life,'' said Diego Magdaleno, an undefeated super featherweight ranked No. 2 by the World Boxing Association. ''If there is anything that will help me keep from going into the deep end with any kind of severe injury I'm all for it.''
That the study - the first big project for the new center - is based in Las Vegas is fitting because the city is recognized as the boxing capital of the world and is also the headquarters of the Ultimate Fighting Championship. A gala celebrating Muhammad Ali's 70th birthday on Saturday at the MGM Grand - site of most of boxing's major fights in the past two decades - is a fundraiser for the center.
Ali suffers from Parkinson's disease, a degenerative brain condition that some doctors say can be brought on by punches to the head. Ali's own neurologist told The Associated Press last month, however, that he didn't believe the heavyweight great's condition was caused by head blows.
Bernick said much still wasn't known about why some fighters develop Alzheimer's or dementia pugilistica - also known as punch drunk syndrome - while others seem to suffer little from repeated hits to the head. The study, he said, could lead to better ways to predict which fighters are more at risk for brain damage later in their lives.
''Our study is not to prove that getting hit in the head will lead to brain damage. We know that already in some sense,'' he said. ''We know being exposed to repetitive blows to the head is a risk factor to developing these conditions, but you can't prove it in any one person unless you have an autopsy.''
The list of boxers who suffered from brain damage is a long one, and goes back a long way. Louis had dementia symptoms late in life, while Sugar Ray Robinson - who sometimes boxed every other week and fought an astonishing 1,403 rounds in his career - developed Alzheimer's disease in his later years. Jerry Quarry, a heavyweight contender who fought Ali twice, died at the age of 53 from dementia pugilistica, while his brother, Mike, a light heavyweight, died from the same thing at 55.
As far back as 1928, doctors were studying the causes of brain damage in boxing. That year, Dr. Harrison S. Martland told the New York Pathological Society about his observations of fighters:
''Fighters in whom the early symptoms are well recognized are said by the fans to be `cuckoo,' `goofy,' `cutting paper dolls,' or `slug nutty,''' Martland said. ''Punch drunk most often affects fighters of the slugging type, who are usually poor boxers and who take considerable head punishment, seeking only to land a knockout blow. It is also common in second rate fighters used for training purposes, who may be knocked down several times a day.''
Still, there are large numbers of fighters who have never suffered any noticeable brain damage, and doctors have yet to pinpoint why these athletes don't seem to be affected by repeated blows to the head.
''We don't know why two individuals both exposed to the same number of blows and years of fighting, why one person develops chronic brain disorders and one doesn't,'' Bernick said. ''When it comes to cumulative head trauma there are many, many things we just don't know.''
During their first visit to the clinic, fighters are given an MRI and a series of cognitive and memory tests. They are tested for judgment and reasoning, and doctors look for signs of impulsiveness and depression. The tests will be used as a baseline for annual checks, and researchers will study all the data to see if there are common links.
''We would hope it would go on forever, but we need at least four years,'' Bernick said. ''We hope to learn enough by then to give us some insight into what happens in real time to individuals involved in activities where they are exposed to head trauma.''
Bernick said the study may provide valuable information that can be used in other sports, like American football, where concussions are an ongoing issue. The Cleveland Clinic is also involved in concussion studies, including one which looks into the effectiveness of a blood test in identifying concussions in college football players.
Boxing promoter Bob Arum said he welcomes the study, which, he said, could be particularly useful when a boxer is deciding how long he will fight.
''A lot of questions people have about when is enough enough will be able to be somewhat solved by what's being done there,'' Arum said. ''We'll have a body of facts and evidence that we never had before.''
Magdaleno, who has been fighting since the age of 8 and has had 132 amateur and 21 professional fights, went with his brother, Jesse, also a professional fighter, for his first test at the clinic. He plans to take the battery of tests after his March 23 fight against Miguel Beltran Jr. in Tucson, Arizona.
''When I first heard about it I wasn't too interested because I didn't understand it all,'' he said. ''But after it was explained to me, I'm all for it. I want to be an inspiration to others and make them come in and do their tests, too.''
