We propose recruiting a total of 150 subjects with ages ranging from 18 to 99 including 3 groups: (1) mTBI+/RHI+: 50 patients with diagnosed mild traumatic brain injury (mTBI) and with the history of organized contact-sports; (2) mTBI-/RHI+: 50 age (by decades) /sex-matched participants that has a history of organized contact-sports but without diagnosed mTBI; (3) mTBI-/RHI-: 50 age (by decades)/sex-matched control participants with no history of organized contact-sports and no diagnosis of mTBI. It is not anticipated that these subjects will have mild cognitive impairment (MCI) from the TBI. MCI is a syndrome defined as a cognitive decline greater than expected for an individual’s age and education level but that does not interfere with activities of daily living.

Group 1 recruitment mTBI+/RHI+:

Residents of Olmsted County, Minnesota who were diagnosed with mTBI will be identified by using the medical-records linkage system of the Rochester Epidemiology Project (REP) between 2017 and 2020. The REP indexes all medical information of individuals residing and receiving care in Olmsted County, Minnesota. Individuals will be identified if they had a diagnostic code in the medical records suggestive of a potential head injury (Table 1),then the medical records will be reviewed for the dates of the specific codes and determined whether a mTBI occurred based on the Mayo Classification System for TBI severity (Definite, Probable, and Possible). By this definition, a “Definite” TBI had to have at least one of the following: loss of conscious of ≥30 minutes, post-traumatic anterograde amnesia of ≥24 hours, intracerebral hematoma, subdural hematoma, epidural hematoma, cerebral contusion, hemorrhagic contusion, penetrating TBI (dura penetrated) or subarachnoid hemorrhage; a “Probable” TBI had to have at least one of the following: loss of consciousness of momentary to <30 minutes, post-traumatic anterograde amnesia of momentary to <24 hours, or depressed, basilar, or linear skull fracture; a “Possible” TBI had to have at least two of the following: blurred vision, confusion (mental state changes), dazed, dizziness, focal neurologic symptoms, headache, or nausea.

If the “Probably” or “Possible” TBI criteria apply to the trauma event, the event will be considered as a mTBI.

The participation of organized contact-sport will be self-reported. Potential participants will be approached with the phone script and/or the letter. If the patient expresses willingness to participate, we will send him/her the follow-up letter or email with a tentative study visit date according to his/her preference. The consent form will be enclosed with the letter/email for his/her review. The questionnaire about the history of contact-sports play will also be enclosed.

Table 1- Codes for traumatic brain injury-related emergency department visits and hospitalizations as recommended by Center for Disease Control and Prevention

Description

ICD-9-CM Codes

Concussion

850

Cerebral laceration and contusion

851

Intracranial injury of other and unspecified nature

854

Injury to optic nerve and pathways

950.1-950.3

Head injury, unspecified

959.01

Inclusion Criteria for Group 1 (mTBI+/RHI+):

1. A history of “Possible” or “Probably” TBI as defined above.
2. A history of participating in at least one organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 1 (mTBI+/RHI+):

1. A history of “Definite” TBI as defined above.
2. A history of chronic neurological disease;
3. Pregnancy or breastfeeding;
4. Inability to provide consent.

Group 2 and Group 3 recruitment:

Recruitment of these paid, groups 2 and 3 participants will be conducted (1) through established Mayo Clinic Rochester research study advertisements, and (2) through Mayo Clinic Study of Aging (MCSA) that provides a list of Olmsted County, MN residents who enrolled in MCSA, from whom matched control will be drawn. The participation of organized contact-sport will be self-reported.

Inclusion Criteria for Group 2 (mTBI-/RHI+):

1. A history of participating in at least one organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
2. No history of “Definite”, “Possible” or “Probably” TBI as defined above.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 2 (mTBI-/RHI+):

1. A history of chronic neurological disease;
2. Pregnancy or breastfeeding;
3. Inability to provide consent.

Inclusion Criteria for Group 3 (mTBI-/RHI-):

1. No history of participating in any organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
2. No history of “Definite”, “Possible” or “Probably” TBI as defined above.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 3 (mTBI-/RHI-):

1. A history of chronic neurological disease;
2. Pregnancy or breastfeeding;
3. Inability to provide consent.

The 3 groups will be age- (by decades) and sex-matched. We will start by recruiting the 3 groups together for the efficiency of data collection. During the recruitment process, if we notice a certain age range or sex is lacking, we will focus on targeting this particular age group or sex group to ensure the maximum matching. For example, if we particularly looking for 18-25-year-old male volunteers with no history of contact-sports participation in group 3, we will have a 2nd advertisement focusing on this particular age group and/or sex group.

Remuneration of $75 will be provided for each participant. If the participant were asked to return for additional imaging, remuneration of $75 will be provided for each visit.

All subjects will be carefully screened by MRI personnel to be certain that they do not have any contraindication to an MRI exam such as foreign bodies in the brain or eye or an incompatible device such as a cardiac pacemaker. This safety screening is part of the routine clinical practice and is performed before any subject is permitted to enter the scanning room. The patients and parents will be given the option of withdrawing from the study at any point in the project without jeopardizing their medical care at Mayo Clinic. Patients requiring sedation to complete the MRI will be excluded from the study.

Pregnant or nursing women are not eligible to participate in this study.  If the participant wishes to participate with the study she will be asked about her pregnancy status.  If she thinks she may be pregnant or if she is unsure of her pregnancy status, she will be offered a no-charge urine pregnancy test before proceeding with any study visit imaging.

We will attempt to recruit an equal number of men and women, but the final proportions will be dependent upon the available subjects in the disease group. Although we will make every effort to include minority subjects, most of the subjects enrolled in Rochester will be of Caucasian background which is a reflection of the regional demographics.

If there is a question on whether or not the subject has the capacity to provide informed consent, the investigator or a member of the study team will assess the patient by reviewing questions regarding the study such as:

1. Can you tell me the purpose of this study?
2. Do you have to be in this study?
3. Can you tell me what will happen if you agree to take part in this study?
4. What will happen to you if you choose not to be in the study?

If it is determined that the subject does not have the capacity to provide informed consent, the subject will then be excluded from the study.

The investigator or coordinator will meet with the potential participants in a private consult room to review and discuss the details of the study using the informed consent document as a guide. The discussion will include all of the elements of informed consent. Potential participants will be given an opportunity to ask questions and we be provided a copy of the informed consent document.