Cognitive Dysfunction and Depression in Retired NFL Players

Abstract and Commentary

By Nitin K. Sethi, MD, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Sethi reports no financial relationships relevant to this field of study.

Synopsis: In former, aging, National Football League players, fluid-attenuated inversion recovery scans showed increased total and deep white matter hyperintensity volumes, while diffusion tensor imaging showed decreased fractional anisotropy reflecting white matter disruption, and this is associated with cognitive impairments and depression.

Source: Hart J Jr, et al. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: A cross-sectional study. JAMA Neurol 2013;70:326-335.

The perils of multiple concussions sustained during contact sports— such as boxing, mixed martial arts, American football, and ice hockey — are increasingly being recognized. Recent medical evidence links multiple concussions sustained during contact sports to later life development of cognitive impairment and behavioral and mood changes in athletes. Recent suicides among former National Football League (NFL) players and postmortem diagnosis of chronic traumatic encephalopathy (CTE) in athletes with a history of multiple concussions has generated a flurry of research to identify neuropsychiatric and neuroimaging correlates of repeated concussions and CTE.

Hart and colleagues investigated the frequency of cognitive impairment and depression in aging former NFL players using neurocognitive tests, clinical neurological assessments, and neuroimaging protocols including fluid-attenuated inversion recovery (FLAIR) MRI, diffusion tensor imaging (DTI), hemosiderin scanning, and arterial spin labeling (ASL). They examined 34 retired players, ages 41 to 79 (mean age = 61.8). Twenty-six of 34 underwent detailed neuroimaging studies (eight players had severe claustrophobia and were unable to tolerate imaging) and were compared with an age, sex, and educationally matched normal group. Cognitive deficits in naming, word finding, episodic memory (verbal and visual), and depression were found to be more common in aging former NFL players who reported a history of multiple concussions compared to matched healthy controls with no history of concussion. FLAIR scans showed increased total and deep white matter hyperintensity volumes while DTI scans showed decreased fractional anisotropy, reflecting white matter disruption in former NFL players who reported multiple concussions during their athletic careers. ASL studies were variable, with some players showing increased blood flow in frontal and cingulate areas, and others showing decreased blood flow. The authors recommend future studies of larger samples of professional athletes with multimodal neurobehavioral and neuroimaging studies and correlation with autopsy findings to confirm these preliminary results.


Signs of early CTE have been identified in the brains of former NFL players at autopsy. An association between repeated concussions and mild cognitive impairment has been suggested.1,2 Whether multiple concussions may also lead to amyotrophic lateral sclerosis is an ongoing debate. At present, CTE can only be conclusively diagnosed by postmortem examination of the brain. There is an urgent need for distinct neuroimaging and neurocognitive biomarkers to help identify the disease process during its early stages of evolution so that both professional and amateur athletes can be protected from the devastating consequences of chronic traumatic brain injury.3 The Hart study identifies MRI biomarkers that measure white matter disruption and further strengthens the evidence for structural and functional dysfunction in the cortical and subcortical pathways, suggesting that a dynamic process may underlie the cognitive and neuropsychiatric dysfunction in aging retired NFL players who sustained multiple concussions during their professional football careers.


1. Guskiewicz KM, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery 2005;57:719-726.

2. De Beaumont L, et al. Long-term functional alterations in sports concussion. Neurosurg Focus 2012;33:E8:1-7.

3. Diaz-Arrastia R, Perl D. Cognitive dysfunction and contact sports. JAMA Neurol 2013;70:301-312.