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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Cogn Behav Neurol. 2020 Sep;33(3):208–217. doi: 10.1097/WNN.0000000000000240

Mild Cognitive Impairment in Retired Professional Football Players With a History of Mild Traumatic Brain Injury: A Pilot Investigation

Nyaz Didehbani *, Lindy M Fields *, Kristin Wilmoth *, Christian LoBue *,†, John Hart *,‡,§, C Munro Cullum *,†,§
PMCID: PMC7479764  NIHMSID: NIHMS1608275  PMID: 32889953

Abstract

Background:

Traumatic brain injury (TBI) is a known risk factor for neurodegenerative dementias such as Alzheimer disease (AD); however, the potential risk of mild cases of TBI, such as concussions, remains unclear.

Objective:

To explore whether a small sample of retired professional athletes with a diagnosis of mild cognitive impairment (MCI)—the prodromal stage of AD—and a history of multiple mild TBIs exhibit greater neuropsychological impairment than age-matched nonathletes with MCI and no history of TBI.

Method:

Ten retired National Football League players diagnosed with MCI and reporting multiple mild TBIs, and 10 nonathletes, also diagnosed with MCI but with no history of TBI, completed a standard neurologic examination and neuropsychological testing. Independent samples t tests were conducted to examine differences in neuropsychological performance between the two groups.

Results:

The retired athletes with a history of mild TBI obtained generally similar scores to the nonathlete controls on measures of verbal learning and memory, verbal fluency, and processing speed. However, the retired athletes scored lower than the controls on tests of confrontation naming and speeded visual attention.

Conclusion:

Retired athletes with MCI and a history of mild TBI demonstrated similar neuropsychological profiles as nonathlete controls despite lower scores on measures of confrontation naming and speeded visual attention. These findings suggest that a history of multiple mild TBIs does not significantly alter the overall neuropsychological profile of individuals with MCI; confirmation of this will require longitudinal research with larger sample sizes.

Keywords: mild traumatic brain injury, athlete, aging, mild cognitive impairment

As the life span of individuals continues to increase, research of neurocognitive disorders and neurodegenerative conditions continues to grow. In particular, research into aging, memory, and neurodegenerative disease has recently increased its focus on identifying the risk factors and early markers for early cognitive impairment (ie, mild cognitive impairment [MCI]) and downstream dementias, such as Alzheimer disease (AD). Understanding how lifestyle and/or traumatic factors experienced earlier in life, such as mild traumatic brain injury (mTBI) or concussion (hereafter referred to as mTBI) during athletic sports, may relate to worsening of cognitive function years, or even decades, later (Isoniemi et al, 2006) is an important research topic.

Mild Cognitive Impairment

In many cases, MCI represents the transitional stage between normal aging and the onset of dementia, where there are subtle cognitive symptoms that may include a decline in memory, attention, executive function, or language, that do not interfere significantly with an individual’s daily functioning (American Psychiatric Association, 2013; Petersen, 2011). Individuals with MCI can be classified into subtypes based on a significant presence of a memory impairment, typically episodic memory, which is the memory for everyday events. Individuals diagnosed with MCI who exhibit a significant memory impairment are categorized as amnestic MCI (aMCI), whereas those without a significant memory impairment but with a significant impairment in another cognitive domain (eg, attention, executive function, language, visuospatial) are categorized as nonamnestic MCI (non-aMCI) (Petersen et al, 2018). The two major clinical subtypes (amnestic vs nonamnestic) may be further divided into single- or multiple-domain MCI depending on the number of cognitive domains (eg, memory, attention, executive function, language) that are significantly impaired.

The incidence of MCI increases with age worldwide (Katz et al, 2012); it is reported to be 6.7% between 60 and 64 years, 8.4% between 65 and 69 years, 10.1% between 70 and 74 years, 14.8% between 75 and 79 years, and ~25% between 80 and 84 years (Petersen et al, 2018). Additionally, ~10–15% of individuals with MCI develop dementia each year (Farias et al, 2009; Geda, 2012). Higher rates of conversion are typically observed from aMCI to AD compared to other types of dementia such as vascular dementia (Mitchell and Shiri-Feshki, 2009).

There are a number of known risk factors for MCI; most important are increased age, male gender, low level of education, and incidence of traumatic brain injury (TBI) (LoBue et al, 2016a). Although once defined as primarily a memory impairment (Petersen et al, 1999), the understanding of MCI evolved in the next decade (Jak et al, 2009). Now, MCI is shown to involve a variety of clinical subtypes as described earlier based on cognitive impairment (amnestic vs nonamnestic and single vs multiple domain) across multiple cognitive domains, not just memory (Bondi et al, 2008; Delano-Wood et al, 2009; Manly et al, 2005; Tabert et al, 2006).

Approximately 10% of individuals annually diagnosed with MCI go on to develop dementia, with ~8% developing AD and 2% developing vascular dementia (Mitchell and Shiri-Feshki, 2009). Other individuals with MCI may show a fluctuating course of progression with impairments followed by improvements, and still others may remain stable for years (Petersen, 2011). A longitudinal study by Aerts et al (2017) demonstrated that approximately half of the individuals with MCI from a community sample in Sydney, Australia, reverted back to normal cognition at some point across four biennial follow-up assessments, dependent on MCI clinical subtype. Those individuals with single-domain MCI, for example, were more likely than those with multiple-domain MCI to revert to normal cognition. However, all of the individuals who had been diagnosed with MCI at baseline were still at an increased risk of developing dementia across the 8-year study compared to cognitively intact individuals. Aerts and colleagues (2017) also found that individuals with an aMCI diagnosis were at an increased risk of developing dementia compared with those with a non-aMCI diagnosis.

Traumatic Brain Injury

Increasing evidence supports the notion that a history of TBI at any life stage increases the risk of cognitive impairment in late adulthood as well as the development of neurodegenerative diseases, such as AD (Abner et al, 2014; Barnes et al, 2014; Baumgart et al, 2015; Fleminger et al, 2003; LoBue et al, 2016b). However, there are very little data connecting the impact of TBI, especially mTBI, on the development of MCI, and the limited research that does exist has been mixed. Nevertheless, recent research has demonstrated that individuals with a history of mTBI that included a loss of consciousness for >5 minutes were diagnosed with MCI on average 2.3 years earlier than those without a history of TBI (LoBue et al, 2016a). Retired athletes with MCI, who may have experienced increased exposure to potential head impact, have also been reported to experience an earlier onset of MCI symptoms compared to nonathlete controls (Erlanger, 2015).

A history of mTBI such as sports-related concussions has been found to be related to later-in-life cognitive difficulties in retired professional athletes in several investigations. For example, Hart et al (2013) found that cognitive impairment (including MCI and dementia) was diagnosed at a higher rate in a sample of 34 retired National Football League (NFL) players compared to the general age-matched population, with 23% of the retired NFL players diagnosed with MCI and 6% diagnosed with some other type of dementia. The retired NFL players with cognitive impairment also demonstrated lower scores on measures of verbal learning, visual memory, confrontation naming, and word retrieval compared to cognitively intact, male NFL players and significantly lower scores than the nonathlete controls. In a cross-sectional sample of retired NFL players ranging in age from 50 to 80 years, Strain et al (2015) noticed smaller hippocampal volumes in these players compared with nonathletes. The retired NFL players also exhibited lower scores for verbal memory—a pattern that became more pronounced with older age. Misquitta et al (2018) also showed that reduced left hippocampal volume was related to worse verbal memory performance in a sample of retired, male Canadian Football League players with a history of mTBI compared to age- and education-matched healthy male controls without a history of mTBI.

In contrast, Randolph et al (2013) compared the cognitive profiles of retired NFL players with probable MCI, based on an initial 8-item self-report informant screener (AD8) and brief in-person cognitive screener, to a nonathlete clinic sample with confirmed aMCI. The authors found no neuropsychological differences between the two groups but did note a higher prevalence of cognitive impairment in the retired NFL players compared to the nonathlete controls. However, it is important to note that the retired athlete group was significantly younger than the nonathlete control group by an average of 13 years (P < 0.0001). This difference is problematic because increased age is a risk factor for developing MCI, and it is difficult to compare the athlete MCI group to the nonathlete MCI group with such a significant age difference. The study by Randolph and colleagues (2013) also did not provide any information on mTBI history in either sample, making it difficult to draw conclusions on the potential impact of head injury on later-in-life (>50 years) cognitive impairment. Thus, it remains unclear whether the severity of memory and cognitive symptoms in individuals with MCI may be pathogenically conferred by a history of recurrent mTBI (such as from a professional career in a highly physical contact sport, thereby resulting in worse symptoms than in individuals with MCI and no history of mTBI).

We conducted our study to expand on previous investigations of individuals with MCI and mTBI in order to determine whether retired athletes with MCI and a history of multiple mTBIs show greater neuropsychological impairment compared with nonathletes with MCI but no history of mTBI. We hypothesized that the retired athletes would demonstrate lower neuropsychological test scores on measures of verbal learning and memory, language (ie, confrontation naming and verbal fluency), speeded visual attention, and processing speed compared with the nonathletes.

METHOD

Participants

Study participants included 10 retired, male NFL players with a history of multiple mTBIs (taken from a larger, ongoing longitudinal study) matched on age, sex, race, and education with 10 male nonathletes without a history of TBI, all of whom had been diagnosed with MCI. Our retired athlete sample consisted of retired NFL players ranging in age from 64 to 77 years (M = 71.70; SD = 4.06) and in education length from 15 to 16 years (M = 15.90; SD = 0.32). The NFL career length in this sample ranged from 6 to 14 years (M = 9.90; SD = 2.60), and retirement time ranged from 32 to 50 years (M = 40.30; SD = 5.96). Nine of the athletes were Caucasian, and one was African American. All 10 retired athletes self-reported a history of mTBIs (ranging from 2 to 4; M = 8.0), four of whom reported a history of multiple incidents of mTBI (ranging from 1 to 14; M = 4.0) with a loss of consciousness. The age of the nonathlete controls ranged from 55 to 83 years (M = 67.76; SD = 8.30), and the education length ranged from 10 to 20 years (M = 15.50; SD = 3.38). Nine of the nonathletes were Caucasian, and one was African American, as in the retired athlete group (Table 1).

TABLE 1.

Demographic Information for the Athletes and Nonathletes

 Characteristic Athlete Nonathlete P
Age (years) 71.70 (4.06) 67.76 (8.30) 0.2
Education (years) 15.90 (0.32) 15.50 (3.38) 0.72
TBI 8.00 (4.30) 0 —
Race 9 C, 1 AA 9 C, 1 AA —
NFL career length (years) 9.90 (2.60) — —
Time since retirement (years) 40.30 (5.96) — —
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Data are provided as M ± SD unless otherwise indicated.

AA = African American. C = Caucasian. TBI = traumatic brain injury.

The inclusion criteria for the retired athlete sample was retired, male NFL players with a clinical diagnosis of MCI and a history of mTBIs. A clinical diagnosis of MCI was made based on standard criteria that included a reported cognitive complaint; evidence of impairment in memory or another cognitive domain, as evidenced by neuropsychological testing; relatively intact daily functioning; and criteria for dementia not met (Petersen, 2004). If the primary cognitive impairment included memory, the MCI diagnosis was further defined as amnestic type, whereas prominent cognitive impairment in other domains was defined as nonamnestic type. Athletes were excluded if they met the criteria for dementia or had other severe neurologic or psychiatric disorders. All athletes were also screened for amyotrophic lateral sclerosis during the neurologic exam, and the results were all negative. Inclusion criteria for the nonathletes included male individuals diagnosed with MCI without a reported history of mTBI or other severe neurologic or psychiatric disorders.

Recruitment

The retired athletes were recruited through “word of mouth” and at local meetings organized by the NFL Players Association in North Texas to participate in a longitudinal study of retired athletes on the impact of mTBI on aging. Study assessments have been ongoing for 10 years at approximately 2-year follow-ups. Sample size was limited due to the necessity of recruiting a retired NFL athlete sample. Although we initially were able to identify a larger cohort of retired professional athletes as part of an ongoing longitudinal study (N = 84), only 10 of those athletes met the criteria for MCI. Of these, seven have also been included in our previous publications examining retired, male professional athletes (Hart et al, 2013; Strain et al, 2017). The majority of the athletes from the larger study demonstrated normal cognitive profiles, eight met the criteria for dementia, and 10 (termed cognitive fixed) were noted to have 1–2 nonmemory cognitive deficits post mTBI that had remained stable, with no progression of symptoms.

For a control group, we selected nonathletes with a diagnosis of MCI and no history of TBI from a database at our Alzheimer’s Disease Research Center at the University of Texas Southwestern Medical Center; we matched these individuals to our retired NFL sample on age, sex, race, and education. The study was approved by the institutional review boards at the University of Texas Southwestern Medical Center and the University of Texas at Dallas and was performed according to the ethical guidelines of the Declaration of Helsinki and its later amendments. All participants provided written informed consent prior to participating.

Procedures

The athlete group attended two research visits. The first visit included both a clinical interview and a neuropsychological assessment administered by a licensed clinical neuropsychologist (N.D. or M.C.). The second visit included a structural MRI and standard neurologic exam administered by a behavioral neurologist (J.H.). At the conclusion of the visits, a consensus diagnosis was determined. The nonathlete group completed an initial visit that included a medical history interview, standard neurologic exam, and neuropsychological assessment. Annual follow-ups were also provided to the nonathlete group.

TBI Diagnoses

A self-reported TBI history was taken by J.H. during the clinical interview. The interview included detailed, open-ended questions about each athlete’s TBI history (eg, a description of the injury, any physical and cognitive symptoms following injury, and any incidence and duration of posttraumatic amnesia and loss of consciousness). All of the athletes in the group described symptoms reflective of mTBI, ranging from minor headaches to loss of consciousness of <5 minutes. The athletes’ injuries were classified according to the American Academy of Neurology “Practice Parameter Guidelines for Grading TBI” (American Academy of Neurology, 1997). None of the nonathletes with MCI reported a history of TBI based on a yes/no question about previous head injuries.

MCI Diagnoses

The MCI diagnoses for the retired athletes were determined by consensus of J.H., N.D., and M.C. using neuropsychological data, neurologic exam results, clinical interview information, and neuroimaging (conducted by J.H., N.D., and M.C.) using standard MCI criteria (Petersen et al, 2010). Neuroimaging data were used to rule out confounding neurologic findings that would place the diagnosis of MCI into question, including the presence of strokes or neoplasm or signs of inflammation. Neuroimaging was also used to assess hippocampal/medial temporal lobe atrophy, a finding that would be consistent with a diagnosis of MCI.

The MCI diagnoses for the nonathletes were determined by consensus of J.H. and M.C., using standard MCI criteria (Petersen et al, 2010). Four individuals from each group were diagnosed with single-domain aMCI, three with multiple-domain aMCI, and three with non-aMCI (one in each group had prominent frontal impairments).

Neuropsychological Assessment

All of the study participants completed a neuropsychological assessment using standard neuropsychological tests measuring the following cognitive domains: verbal learning and memory, language, speeded visual attention, and processing speed. Both groups also completed a depression screener as part of the neuropsychological assessment. Because the two groups were selected from two different projects and therefore were administered a range of different neuropsychological measures, for the purpose of the comparisons in this manuscript, we present only the overlapping measures that were administered to both groups.

Athlete Testing

We used the California Verbal Learning Test—Second Edition (CVLT–II; Delis et al, 2000) to assess the athletes’ verbal learning and memory. The CVLT–II test includes five subscores: total score, short delay free recall, short delay cued recall, long delay free recall, and long delay cued recall. We used three measures to assess language: The Boston Naming Test (Kaplan et al, 2001) measures confrontation naming; the Controlled Oral Word Association Test (Benton et al, 1994) and the Animal Fluency test (Goodglass and Kaplan, 1983) measure verbal fluency. For speeded visual attention, we administered the Trail Making Test (Trails A and B) (Tombaugh, 2004); for processing speed, the Coding subtests of the Wechsler Adult Intelligence Scale—Fourth Edition (Wechsler, 2008); and for depression, the Beck Depression Inventory—Second Edition (Beck et al, 1996). The athletes also completed the Vocabulary and Matrix Reasoning subtests from the Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999) to estimate their IQ.

Nonathlete Testing

We administered the same neuropsychological tests to the nonathletes, with a few changes. For verbal learning and memory, for example, we used the original California Verbal Learning Test (CVLT; Delis et al, 1987); for processing speed, we used the Digit Symbol subtest of the Wechsler Adult Intelligence Scale—Third Edition (Wechsler, 1997); and for depression, we used the Geriatric Depression Scale (Yesavage et al, 1982–1983). The nonathletes’ IQs were not measured.

Statistical Analysis

We conducted all statistical analyses using SPSS (Version 23) statistical software. We conducted two independent samples t tests using the Satterthwaite method for unequal variances to compare the demographic variables and neuropsychological scores between the retired athlete and the nonathlete groups’ demographically corrected t scores. T scores for the neuropsychological tests were based on normative samples of age-, sex-, and education-matched individuals. Based on our previous findings from a larger cohort of 34 retired NFL players (Hart et al, 2013; Strain et al, 2015), we used one-tailed analyses to test our hypothesis that the athletes with MCI and a history of multiple mTBIs would score lower on all neuropsychological tests compared with the nonathletes with MCI and no history of mTBI. Our previous findings indicated lower scores on measures of verbal learning and memory and confrontation naming for cognitively intact NFL players compared with cognitively intact matched controls; thus, we anticipated lower scores in a group of retired players with MCI compared with matched controls. The use of a one-tailed analysis is also consistent with prior research with directional hypotheses (Bondi et al, 1995; Matser et al, 2001; Voss et al, 2013). Due to the pilot nature of the study and the small sample size, we did not correct for multiple comparisons, which is consistent with prior research of similar scope and aims (eg, Bondi et al, 1995). We set the alpha level to .05 and used nonparametric tests in this small exploratory study.

RESULTS

MCI Diagnoses

Our results indicated no significant differences between the two groups in age (P = 0.20) or education length (P = 0.72), and the two groups were matched on race. In addition, the athlete and nonathlete groups were equally characterized by specific MCI diagnosis: Both groups included four participants with single-domain aMCI, three with multiple-domain MCI, and three with non-aMCI. Of the three individuals in each group with non-aMCI, one individual in each group had prominent frontal impairments. Table 2 and Figure 1 present the neuropsychological test scores of the two groups. T scores range from 10 to 90, with a score of 50 representing an average mean score; 1 SD is represented in 10-point increments. Individuals diagnosed with single-domain aMCI demonstrated at least 1 SD below the mean on measures of verbal learning and memory (CVLT scores), those diagnosed with multiple-domain MCI demonstrated at least 1 SD below the mean on at least two measures, and those with non-aMCI demonstrated relatively intact verbal memory with a nonmemory test score that was below the mean. Table 3 presents the MCI subtype and neuropsychological test scores for every individual in our study. All scores in Table 3 represent standard t scores, with the exception of longest digit forward and longest digit backward.

TABLE 2.

Participants’ Raw and t Scores on the Neuropsychological Tests

Athletes With MCI and mTBI History (n = 10) Nonathletes With MCI and no mTBI History (n = 10)
Cognitive Domain and Test N M raw score (SD) M t score (SD) M raw score (SD) M t score (SD) t P†
Verbal learning and memory‡
 CVLT total score 19 27.60 (5.91) 38.30 (7.78) 37.44 (5.98) 40.20 (8.99) −.505 0.310
 CVLT SDFR score 19 3.20 (2.97) 34.00 (11.74) 6.44 (1.87) 41.11 (10.54) −1.383 0.093
 CVLT SDCR score 19 5.50 (2.99) 33.50 (12.48) 8.11 (1.01) 43.33 (12.25) −1.730 0.051
 CVLT LDFR score 19 4.10 (2.47) 36.00 (9.37) 6.33 (3.35) 43.33 (10.00) −1.650 0.060
 CVLT LDCR score 19 4.50 (2.92) 32.50 (11.60) 7.22 (3.19) 38.89 (12.69) −1.146 0.134
Language
 BNT score 20 47.60 (7.99) 39.10 (9.09) 53.60 (4.97) 49.50 (14.19) −1.952 0.035*
 COWAT score 20 36.20 (16.44) 46.60 (13.52) 39.80 (7.80) 49.60 (7.50) −.614 0.275
 Animal Fluency score 20 15.90 (3.93) 43.80 (11.22) 18.20 (3.97) 47.80 (10.46) −.824 0.211
Speeded visual attention
 Trails A score 20 37.00 (13.12) 47.90 (8.39) 28.70 (12.15) 55.80 (6.92) −2.297 0.017*
 Trails B score 20 135.90 (71.50) 43.30 (11.91) 80.20 (22.67) 52.30 (6.40) −2.106 0.025*
Processing speed
 Coding score 20 45.70 (14.47) 47.00 (9.80) 44.70 (8.12) 44.90 (8.03) 0.524 0.304
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*

Significant at P < 0.05.

†

One-tailed P values are based on a comparison of the t scores from each cognitive measure.

‡

The CVLT–II and the WAIS–IV Coding subtest were used to measure verbal learning and memory in the retired athletes and the CVLT and the WAIS–III Digit Symbol subtest were used to measure verbal learning and memory in the nonathletes. One of the nonathletes did not fully complete the CVLT, so scores are missing for one person on that measure.

BNT = Boston Naming Test. COWAT = Controlled Oral Word Association Test. CVLT = California Verbal Learning Test. LDCR = Long delay cued recall. LDFR = Long delay free recall. mTBI = mild traumatic brain injury. SDCR = Short delay cued recall. SDFR = Short delay free recall. WAIS = Wechsler Adult Intelligence Scale.

FIGURE 1.

FIGURE 1.

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Mean t scores on neuropsychological measures by group.

†The WAIS–IV Coding subtest was used to measure verbal learning and memory in the retired athletes and the CVLT and the WAIS–III DS subtest were used to measure verbal learning and memory in the nonathletes.

BNT = Boston Naming Test. COWAT = Controlled Oral Word Association Test. CVLT = California Verbal Learning Test. DS = Digit Symbol. LDCR = long delay cued recall. LDFR = long delay free recall. SDCR = short delay cued recall. SDFR = short delay free recall. WAIS = Wechsler Adult Intelligence Scale.

TABLE 3.

MCI Subtype and Neuropsychological Test Scores for Each Individual

Athletes
Diagnosis CVLT SDFR SDCR LDFR LDCR BNT COWAT Animals Trails A Trails B LDF LDB Coding
MCI-amnestic 33 30 40 30 25 37 42 48 49 40 7 3 50
MCI-amnestic 34 20 30 35 30 41 78 53 49 44 7 6 63
MCI-amnestic 32 25 15 20 15 44 55 46 55 48 8 6 50
MCI-amnestic 37 35 30 40 25 55 51 49 50 59 6 3 57
MCI-multiple domains 25 20 15 25 25 26 45 34 52 37 6 4 43
MCI-multiple domains 44 30 45 45 35 48 53 57 36 33 4 3 40
MCI-multiple domains 37 35 30 35 30 38 36 44 62 41 6 4 47
MCI-nonamnestic (frontal) 47 55 55 50 55 26 34 43 49 65 5 4 53
MCI-nonamnestic 44 40 40 35 45 42 34 47 34 42 7 4 37
MCI-nonamnestic 50 50 35 45 40 34 38 17 43 24 6 4 30
Mean 38.3 34 33.5 36 32.5 39.1 46.6 43.8 47.9 43.3 6.2 4.1 47
Nonathletes
Diagnosis CVLT SDFR SDCR LDFR LDCR BNT COWAT Animals Trails A Trails B LDF LDB DS
MCI-amnestic 39 40 30 30 20 49 51 62 53 44 7 3 37
MCI-amnestic 38 40 50 50 50 77 59 52 58 45 8 7 37
MCI-amnestic 34 40 30 40 30 45 49 39 62 55 7 7 47
MCI-amnestic 28 X X X X 37 41 49 58 54 6 4 50
MCI-multiple domains 38 40 30 40 30 37 49 34 54 52 7 4 37
MCI-multiple domains 43 50 60 50 50 35 61 54 55 61 7 7 57
MCI-multiple domains 33 20 40 30 30 56 36 51 59 43 6 4 37
MCI-nonamnestic (frontal) 61 60 60 60 60 45 51 29 61 60 5 6 57
MCI-nonamnestic 42 40 40 40 40 70 53 57 38 53 7 5 47
MCI-nonamnestic 46 40 50 50 40 44 46 51 60 56 4 4 43
Mean 40.2 41.1 43.3 43.3 38.9 49.5 49.6 47.8 55.8 52.3 6.4 5.1 44.9
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BNT = Boston Naming Test. COWAT = Controlled Oral Word Association Test. CVLT = California Verbal Learning Test. DS = Digit Symbol. LDCR = long delay cued recall. LDB = longest digit backward. LDF = longest digit forward. LDFR = long delay free recall. MCI = mild cognitive impairment. SDCR = short delay cued recall. SDFR = short delay free recall.

Neuropsychological Profiles

Overall, both groups (athletes with MCI and mTBI and nonathletes with MCI and no mTBI) had similar neuropsychological profiles, but significant differences were seen on measures of confrontation naming (P = 0.035) and speeded visual attention (Trails A, P = 0.017; Trails B, P = 0.025). Specifically, the retired athletes scored 1 SD lower than the nonathletes on the Boston Naming Test; the athletes scored in the mildly impaired range (t = 39) and the nonathletes scored in the average range (t = 49). The retired athletes also scored significantly lower on measures of simple (Trails A, P = 0.017) and complex (Trails B, P = 0.025) speeded visual attention, although no other differences reached statistically significant levels (Table 2). Estimated IQ was available for the athlete sample, which incorporated scores from the Wechsler Abbreviated Scale of Intelligence Vocabulary and Matrix Reasoning subtests. The athletes’ estimated IQ scores ranged from average to superior (99–121; M = 109.2).

Depression Screening

Depression screening measures were used in both the retired athlete group (Beck Depression Inventory—Second Edition) and the nonathlete group (Geriatric Depression Scale) to screen for this potentially confounding diagnosis. Scores on the Beck Depression Inventory—Second Edition range from 0 to 63, with scores ranging from 0 to 12 indicating minimal symptom endorsement, 13–19 indicating mild symptoms, 20–28 indicating moderate symptoms, and 29–63 indicating severe symptom endorsement. The Beck Depression Inventory—Second Edition scores of the retired athlete group ranged from 0 to 14 (M = 5.6; SD = 4.44). The Geriatric Depression Scale scores range from 0 to 15, with scores ranging from 0 to 4 indicating normal symptom endorsement, 5–8 indicating mild symptoms, 9–11 indicating moderate symptoms, and 12–15 indicating severe symptom endorsement. The Geriatric Depression Scale scores of the nonathlete group ranged from 0 to 3 (M = 1.50; SD = 1.08). Both depression screening measure scores suggest no significant depressive symptom in any of the participants except for one retired athlete who exhibited mild depressive symptoms (Beck Depression Inventory—Second Edition = 14).

DISCUSSION

Neuropsychological Findings

We had hypothesized that the retired athletes with MCI and a history of mTBI would demonstrate lower neuropsychological test scores than the nonathletes with MCI and no mTBI on measures of verbal learning and memory, language, speeded visual attention, and processing speed. In fact, the individuals with MCI both with and without a history of mTBI demonstrated similar neuropsychological profiles across the domains of verbal learning and memory, language, and processing speed. However, significant differences were observed in three of the 11 cognitive test scores measured. Specifically, we found that retired athletes (with a history of multiple mTBIs) scored significantly lower than the nonathletes (with no history of mTBI) on confrontation naming and speeded visual attention. It is unclear why those two domains are significantly different, but some literature has shown language impairment such as confrontation naming following mTBI (Hart et al, 2013; King et al, 2006; Strain et al, 2017). However, there was no significant difference between the retired athletes and nonathletes in the domains of verbal memory, verbal fluency, or processing speed. Overall, our results suggest that a history of mTBI may negatively impact confrontation naming and speeded visual attention in individuals with MCI; however, this remains to be confirmed with a large cohort.

Language Deficits With mTBI

A few of our group’s previous studies examining cognitive function in a sample of retired NFL athletes with and without MCI have also reported lower performance in areas of language (confrontation naming and verbal fluency) and memory. One of these studies examined 25 retired NFL athletes with and without MCI who all had a history of mTBI compared with a sample of 22 age-, sex-, and education-matched healthy nonathlete controls with no history of TBI (Strain et al, 2017). The retired NFL players with and without MCI scored lower than the controls on confrontation naming, and poorer performance on naming correlated with decreased white matter integrity for the retired athletes but not the controls. This finding demonstrates that white matter pathology is associated with poorer performance in naming in retired athletes with mTBI that is different than the pathology of normal aging in nonathletes without a history of TBI (Strain et al, 2017).

Differences seen specifically in word finding in individuals with mTBI may be related to a disruption of the left frontotemporal area, as was noted in our group’s EEG study of retired athletes ages 37–63 years (Fratantoni et al, 2017). The frontal region of the brain is vulnerable to damage from head trauma, and the left frontotemporal region is an integral part of the language circuit. During a word retrieval task, Fratantoni et al (2017) found differences in evoked response potential amplitude over the left frontotemporal region in 19 healthy, male controls compared to no change in a group of 19 cognitively intact, retired NFL players. Neuroimaging studies may provide insight into areas of the brain that are altered following mTBI, but longitudinal studies with frequent follow-up are needed to explore brain changes in relation to behavioral and neurocognitive changes.

King et al (2006) also reported poorer performance on a word retrieval task in 10 young adults (M age = 28.8, SD = 8.1) with mTBI compared with an age- and sex-matched control group without mTBI. The authors administered several language-based tests and found again that naming may serve as a sensitive marker of language impairment during the acute stage following mTBI. While King and colleagues (2006) and Frantantoni and colleagues (2017) indicated poorer performance in language tests (eg, naming) in primarily cognitively intact individuals with and without a history of TBI, the current results indicate similar findings in individuals with MCI. Additionally, our group (Hart et al, 2013) demonstrated lower performance in areas of language (confrontation naming and word retrieval) and memory in cognitively impaired (ie, MCI and dementia) NFL players (which included seven of the 10 retired athletes in the current sample) compared with cognitively intact NFL players and cognitively intact controls without a history of TBI. These findings, combined with results of the current study, suggest that poorer performance on naming following acute mTBI may persist throughout the aging process.

Other investigations examining former college athletes in late adulthood who had a history of mTBI have shown poorer performance in verbal fluency and episodic memory tasks compared with former college athletes without a history of mTBI (De Beaumont et al, 2009; Tremblay et al, 2013). Baker et al (2018), for example, compared the frequency of MCI diagnoses in a group of 21 retired athletes who had participated in contact sports (including NFL and National Hockey League) with a group of 21 athletes who had participated in noncontact sports (eg, swimming, cycling, or running). The contact-sport athletes had an average of 8.7 reported mTBIs; no information was given for the noncontact-sport athletes. Overall, Baker and colleagues (2018) did not find a significant difference in MCI diagnosis frequency between the two groups, but they did find that the contact-sport athletes performed significantly worse on one measure of language (letter fluency) and one memory score (verbal recall list B) than the noncontact-sport athletes. There were no significant differences across other measures of language (naming or category fluency), nor on measures of memory, executive function, attention, or visuospatial skills (Baker et al, 2018). Conversely, in a large sample of 758 retired professional football players who had been exposed to repetitive contact, Guskiewicz et al (2005) demonstrated that the frequency of MCI diagnosis and self-reported memory impairment was fivefold and threefold higher, respectively, in athletes with a history of >3 mTBIs than in athletes with no history of mTBI. Although some research has shown that a history of multiple mTBIs may be associated with cognitive vulnerability later in life on some measures of language (naming and verbal fluency) and verbal memory (immediate recall), our findings indicated relatively similar cognitive profiles in individuals with a diagnosis of MCI with and without a history of mTBI on measures of verbal memory, language (verbal fluency), and processing speed.

Pathological Burden of mTBI

There is evidence that head injuries early in life may induce and/or accelerate the development of cognitive impairment and dementia, as noted in a study by LoBue et al (2016a), who reported that individuals with comorbid MCI and TBI had been clinically diagnosed with MCI on average 2 years earlier than individuals with MCI and no history of TBI. In a review, Ramos-Cejudo et al (2018) suggested that TBI in some individuals may trigger an accumulation of pathological burden, reduce neuronal reserve, and trigger neurodegenerative mechanisms. The review included examination of both animal and human models and concluded that cerebrovascular dysfunction following TBI may cause deposits of Aβ/tau and early initiation of AD-like pathology.

Alosco et al (2018) examined levels of the microtubule-associated protein tau, which is implicated in AD pathogenesis, in the cerebrospinal fluid of 68 retired professional athletes who had been exposed to repeated head impacts and compared those levels to cerebrospinal fluid total tau load in age-matched, healthy nonathletes without a history of TBI. In that study, the estimated number of lifetime head impacts (across at least 12 years of organized football) was shown to correlate with higher cerebrospinal fluid tau levels (Alosco et al, 2018). Because tau is known to accumulate into neurotoxic aggregates and cause synaptic dysfunction in the AD brain, it could potentially serve as a mechanistic link between TBI and downstream cognitive impairment and dementia. However, Alosco and colleagues (2018) found similar total tau levels in the retired athletes and healthy controls; thus, while a link between early neuropathology and neurocognitive impairment was not drawn in their study, it does suggest that exposure to multiple head impacts may induce neuropathological changes in the brain.

Nonhuman studies lend further support for an association between TBI and AD pathology. In a study by Kondo et al (2015), mice were shown to develop increased levels of phosphorylated tau (p-tau) up to 48 hours after sustaining a single mTBI, a single severe TBI, or repetitive mTBIs. TBIs were inflicted on the mice by dropping a 54-gram metal bolt to the dorsal part of the skull. Mice in the repetitive mTBI group experienced seven mTBIs across 9 days. While the p-tau levels were shown to recover to baseline within 14 days in the mice that had sustained a single mTBI, the mice that had sustained a severe TBI or repetitive mTBIs continued to exhibit elevated p-tau concentrations for up to 6 months. This sustained tau pathology was associated with neuronal loss in the cortex and hippocampus (Kondo et al, 2015). These animal data provide additional evidence in vivo that multiple mTBIs may increase levels of p-tau that persist for months.

Future Direction

Additional prospective investigations into MCI risk with a larger sample of retired athletes and nonathletes with and without a history of mTBI can provide insight on whether our findings are specific to a remote history of sports-related concussion or reflect mTBI more generally. It is also important to examine whether a history of TBI may accelerate the progression of MCI. The findings of the current pilot study did not address potential differences in progression between individuals with MCI with and without a history of mTBI. Further longitudinal examination of the relationship between mTBI and MCI with larger sample sizes will help to advance our understanding in this area, as there is still no direct link between a history of mTBI and definitive long-term neurocognitive decline.

Study Limitations

Overall, this pilot investigation had several limitations that may affect its generalizability. A potential limitation was the recruitment of the athlete and nonathlete groups from two separate projects, although both projects occurred within the same institution, with overlapping project investigators and personnel. As a result, a different test battery was administered to each group (athlete vs nonathlete). Due to the brief neuropsychological assessment that was conducted as part of a larger investigation, and differences in test forms across the samples, we were unable to examine other cognitive domains such as executive function and visual memory, so differences in those areas might exist. It is important to investigate a more expansive set of cognitive domains to fully understand cognitive profiles of both MCI groups and to examine other areas of strengths or weaknesses in the groups.

Additionally, we did not have estimated IQ scores on the nonathlete group due to differences in study protocols, although their mean education levels were similar. It is important to note that actual educational experiences may differ, and we were not able to fully match the groups on global functioning. We were also limited to a small sample size given the uniqueness of the retired athlete group. It should also be noted that the current retired athlete sample was recruited from a larger cohort of 84 retired athletes and does not reflect the cognitive profile for all retired NFL players, as the sample was limited to only those retired players who met the criteria for a clinical diagnosis of MCI and who reported multiple mTBIs. For this reason, our sample size was limited to the 10 retired athletes who met the diagnostic criteria for MCI. Thus, due to the small sample size of the study, the generalizability of the results may be limited, and larger investigations examining the potential impact of mTBI on cognitive function in late adulthood are warranted.

As with most studies of individuals with mTBI, we were also dependent on self-reported mTBI history from our athlete population without corroborating medical records, as such records are unavailable. However, there is supportive literature on the consistency of prior mTBI reporting from our larger sample of retired athletes (Didehbani et al, 2017) and from individuals with MCI and AD (Wilmoth et al, 2018). Other potential contributing factors such as a history of drug and alcohol use, pain level, sleep quality, and current medications were not assessed in this study, which may have influenced the participants’ cognitive functioning.

CONCLUSION

Our findings suggest that a history of multiple mTBIs does not significantly alter the overall neuropsychological profile of individuals with MCI. In our study, athletes with MCI and a history of mTBIs demonstrated relatively similar cognitive profiles as nonathletes with MCI and no history of mTBI, with the athletes showing significantly lower scores only on measures of confrontation naming and speeded visual attention. Together with the reported association between mTBI history and earlier onset of MCI (Lobue et al, 2016a), these findings suggest a potential influence of mTBI primarily on confrontation naming later in life. Our study highlights the clinical importance of assessing cognitive function, including tests of language and speeded attention, on a routine basis with individuals after mTBI in order to track change across multiple cognitive domains beyond memory.

Acknowledgments

Supported in part by the Texas Alzheimer’s Research Consortium funded by the state of Texas through the Texas Council on Alzheimer’s Disease and Related Disorders, the University of Texas Southwestern Alzheimer’s Disease Center (NIH P30 AG12300), the Texas Institute for Brain Injury and Repair in the O’Donnell Brain Institute at the University of Texas Southwestern Medical Center, and the Rainwater Foundation.

Glossary

AD

Alzheimer disease

aMCI

amnestic mild cognitive impairment

CVLT

California Verbal Learning Test

MCI

mild cognitive impairment

mTBI

mild traumatic brain injury

NFL

National Football League

p-tau

phosphorylated tau

TBI

traumatic brain injury

Footnotes

The authors declare no conflicts of interest.

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