No agreement on CTE progression
Not only is there no unanimity about whether CTE constitutes a distinct neurodegenerative disease, but experts disagree about how it should be classified. One of the two main research groups studying CTE (the CSTE group led by Drs. Ann McKee, Robert Stern and Robert Cantu) classifies CTE into four disease "stages" [21] while the other (led by Dr. Bennett Omalu) describes four "phenotypes"). [20, 22]
According to McKee and her colleagues, the four stages are:
Stage 1: preclinical. No symptoms.
Stage 2: Deterioration in attention, concentration, and memory, as well as disorientation and confusion, and occasionally accompanied by dizziness and headaches.
- Symptom onset: The first symptoms in confirmed cases of C.T.E. were noticed at ages between 25 and 76 years, with a mean of 42.8 years.
- One third were symptomatic at time of retirement from sport;
- Half were symptomatic within 4 years of stopping play.
Stage 3: Social instability, erratic behavior, lack of insight, poor judgment, memory loss and initial symptoms of Parkinson disease
Stage 4: General cognitive disfunction progressing to dementia, often accompanied by full-blown Parkinsonism, as well as speech and gait abnormalities.
As other studies have noted, the stages proposed by McKee et al [21] are based on the level of neuropathological evidence of disease on autopsy rather than on clinical presentation. [19] In light of the lack of currently available biomarkers to observe the natural history of CTE in living patients, Dr. Barry Jordan, the author of a 2013 study reviewing the clinical spectrum of sport-related traumatic brain injury,[20] viewed the characterization of pre-clinical CTE (before symptoms are observed) and prodromal CTE (between the time initial symptoms appear and onset of the full blown disease) as premature. Instead, Jordan proposed classifying the clinical criteria for the diagnosis of CTE into four categories (definite, probable, possible, and improbable CTE) in line with other neurological disorders. His view appears to be shared by Randolph in his 2013 NFL retiree study,[26] in which Randolph notes a "substantial pathological overlap and a lack of clear clinical-pathological correlation."
On the basis of currently available evidence, the Gardner study[19] proposed a fourth, conservative, operational definition for the modern CTE diseased process:
- A presenting clinical profile that includes (but is not limited to) cognitive (e.g. attention and memory) and mental health problems.
- A specific neuropathology involving only specific regions of the brain characteristic of the disease, and in the absence of other neuropathology; and
- The absence of any other disease or disorder that may conceivably explain the clinical or pathological findings.
CTE: not as common as believed?
Although historically, CTE was primarily associated with boxing, it has been identified among athletes playing American football, hockey, wrestling, rugby and among those suffering blast or concussive injury in military service. [13]
A 2012 study [13] by CSTE researchers found evidence of CTE in 80% of a small group of deceased individuals with a history of repetitive mild traumatic brain injury (64 athletes, including 33 former NFL players, and 21 military veterans), from which evidence the authors concluded that "repetitive mild traumatic brain injury alone is sufficient to trigger CTE in some people." (emphasis supplied)
The Gardner study [19] estimated, however, the incidence of CTE among professional American football players at less than 4%, based on the numbers of cases obtained in a given period versus the number of athletes who died during the same period. If all of those professional athletes at risk were to be used as the exposure, the study authors argue, then the incidence rate would be less than 1/100th of a percent (0.01%). Gardner estimated that of the 85 autopsies only 20% had 'pure' neuropathology consistent with CTE, 52% had CTE plus other neuropathology, 5% had neuropathology but no CTE, and 24% had no neuropathology.
For his part, Dr. Randolph, the author of the 2013 study on NFL retirees,[26] said he believed that, if there was indeed an increased risk of late-life cognitive impairment in NFL retirees compared to men in the general population, it was probably due to diminished cognitive reserve. "We still do not know if NFL players have an increased risk of late-life neurodegenerative disorders," Randolph said.[28]
The idea that concussion may speed up the brain's natural aging process and lead to a more rapid depletion of cerebral reserve is consistent with a theory advanced by researchers at the University of Michigan in a 2012 study[27] of collegiate athletes with a history of concussion in which they found subtle changes in concussed athletes on tests of balance and gait that, they speculated, put the athletes at greater risk of falls later in life.
