In a new study of former athletes with chronic traumatic encephalopathy (CTE), researchers have found the disease tends to show up in one of two ways: early, with depression and behavioral changes, or later, with memory loss.
Researchers talked to the relatives of 36 people who had the brain condition identified on an autopsy and found all but three had shown symptom patterns that followed one of those two trajectories.
Experts not involved in the study called it a "marginal step" or "first stab" at determining the course of the disease, but said what is now needed are studies that track and test living athletes after a head injury.
"The findings are certainly consistent with what other studies have been pointing to with this condition," Dr. Ramon Diaz-Arrastia, who studies traumatic brain injury at the Uniformed Services University of the Health Sciences in Rockville, Maryland, said.
But, he added, "We need to be able to have a way, during life, that we can make a diagnosis of this condition."
CTE is a degenerative brain disease that has been found in deceased athletes who suffered repeat concussions and other blows to the head during their careers. The condition gained national attention following the recent suicides of several retired hockey and football players, including former San Diego Chargers star Junior Seau in 2012.
For the new study, researchers from Boston University's Center for the Study of Traumatic Encephalopathy interviewed the family members of 36 former male athletes who had died with CTE, most of them football players. They also reviewed athletes' medical records, when available.
Three of the men had no symptoms of mood or memory disorders at the time of their deaths.
Of the remaining 33, two-thirds fit into what the researchers called the "behavior/mood group." Their first signs of CTE showed up when they were in their mid-30s, on average, as depression, hopelessness or violent and explosive behavior.
The 11 other former athletes, the "cognition group," showed no symptoms until their late-50s, when they developed impaired thinking and memory skills, Robert Stern and his colleagues reported Wednesday in Neurology.
"What it does is give us a picture of what CTE may look like during life," Stern said.
"Very early studies of boxers also indicated these two presentations," he said. "Why they occur, it's too early for us to really understand."
Diaz-Arrastia, who was not involved in the new research, said that pattern shows up with other forms of dementia as well, such as Alzheimer's disease.
"When the pathology is very severe and manifests at an earlier stage, the psychiatric symptoms seem to dominate the picture," he said.
Neuroscientist Dr. John Hart, Jr. from the University of Texas at Dallas said the new report is limited by the lack of objective neurological test results or depression measures from former athletes before they died.
He said the next step, a big one, will be to start with current athletes and determine how CTE progresses - from head injuries, to mood or memory symptoms, to brain changes visible on scans and autopsies.
Having a clearer picture of the course of the disease will help researchers know where to start looking for treatment and prevention ideas, he said.
"The whole field has to look at, how do we tie these things together?" Hart, who wasn't part of the study team, said.
"There's not just an easy, straightforward answer to what's happening with these folks."
Stern said he is currently working with researchers at Brigham and Women's Hospital putting 100 former football players and 50 former non-contact athletes through a range of neurological and psychiatric tests as well as brain scans and blood tests.
The goal is to develop objective measures of CTE and ways to detect the disease during life.