Neuroimaging Markers for Determining Former American Football Players at Risk for Alzheimer's Disease.

ABSTRACT

NFL players, by virtue of their exposure to traumatic brain injury (TBI), are at higher risk of developing dementia and Alzheimer's disease (AD) than the general population. Early recognition and intervention before the onset of clinical symptoms could potentially avert/delay the long-term consequences of these diseases. Given that AD is thought to have a long pre-clinical incubation period, the aim of the current research was to determine whether former NFL players show evidence of incipient dementia in their structural imaging before diagnosis of AD. To identify neuroimaging markers of AD, against which former NFL players would be compared, we conducted a whole-brain volumetric analysis using a cohort of AD patients (ADNI clinical database) to produce a set of brain regions demonstrating sensitivity to early AD pathology (i.e., the "AD fingerprint"). A group of 46 former NFL players' brain magnetic resonance images were then interrogated using the AD fingerprint, that is, the former NFL subjects were compared volumetrically to AD patients using a T1-weighted magnetization-prepared rapid gradient echo sequence. The FreeSurfer image analysis suite (version 6.0) was used to obtain volumetric and cortical thickness data. The Automated Neuropsychological Assessment Metric-Version 4 was used to assess current cognitive functioning. A total of 55 brain regions demonstrated significant atrophy or ex vacuo dilatation bilaterally in AD patients versus controls. Of the 46 former NFL players, 41% demonstrated a greater than expected number of atrophied/dilated AD regions compared with age-matched controls, presumably reflecting AD pathology.