Head in the Game - a study on long-term effects of playing elite football on brain structure and function

In recent years, sports-related concussions have been the topic of numerous
studies, consensus statements, position papers and media reports 1-4. The most
common acute symptoms of concussion are headache and dizziness, which usually
resolve within 7-10 days 5. However, in 10-15% of concussions persistent
symptoms are reported 6. Further, several pathological case-studies and
case-series have suggested a potential for long-term neurological health
problems in football players and other professional contact sport athletes 7 8.
These may include the development of neurodegenerative diseases (such as
chronic traumatic encephalopathy 9, Alzheimer*s dementia 10 or mild cognitive
impairment 11) and affective disorders (such as depression 12). However, the
proposed association is far from established, mainly due to inappropriate study
designs 13.

Equally controversial is the debate whether repetitive subconcossive blows to
the head (i.e. purposeful heading) have an effect on neurocognitive performance
in football players 14. While some authors suggest heading related deficits of
attention and memory 15 16, others did not find such an association 17 18. A
most recent systematic review 19 found repeat head impacts to play a merely
putative role in the development of neurocognitive deficits and identified
low-quality assessment of heading frequency as a major confounder. With regards
to short- and medium-term consequences, Matser et al. 20-22 found a negative
association between neurocognitive performance and number of previously
incurred concussions in football players. Several subsequent studies were
conducted in active football players yielding inconclusive results 23-34. An
investigation with female university level players suggested that functions
related to cognitive processing speed are most vulnerable and may still be
impaired 6 month after concussion 31. However, in a prospective five-year
follow-up study with a sample of young elite male footballers no significant
neurological, structural brain imaging or neuropsychological changes were found
34.

To date, only four studies evaluated long-term neurocognitive changes in
retired football players, and none included female players 35-38. In the most
recent investigation Vann Jones et al. 38 screened 92 male former professional
footballers for mild cognitive impairment (MCI) or dementia and reported that
the risk of disease falls in line with the general population. Yet, Koerte et
al. 36 39 found an association between repetitive
subconcussive head impacts (RSHI) and neuroinflammation as well as cortical
thinning in a small sample of former professional male football players. Both
markers may precede long-term neurocognitive changes. Therefore, the aim of
this study is to assess (a) neurocognitive performance and (b)
structural/functional abnormalities in brain networks in former elite female
football players compared to a matched control group of former elite female
athletes from noncontact sports.

Primary Objective: The aim of the proposed project is to assess (a)
neurocognitive performance and (b) structure and function of brain networks in
retired female football players compared to a matched control group of retired
female elite athletes from noncontact sports. Further we are interested in an
exploratory analysis of correlates between neurocognitive performance and
potential abnormalities in the connectivity of brain networks. Specific primary
research questions are:

(1) Is there a difference between female retired non-contact sports athletes
and female retired football players in (a) neurocognitive performance and/or
(b) structure/function of brain networks?
(2) Is there a difference between female retired non-contact sports athletes
and female retired football players reporting previous concussions in (a)
neurocognitive performance and/or (b) structure/function of brain networks?
(3) Is there a difference between female retired non-contact sports athletes
and female retired football players reporting frequent heading exposure in (a)
neurocognitive performance and/or (b) structure/function of brain networks?
(4) What is the individual and cumulative effect of (1) previous concussions
and (2) frequent heading exposure on (a) neurocognitive performance and (b)
structure/ function of brain networks in football players?
(5) Are there correlates between neurocognitive performance and potential
abnormalities in structure or function of brain networks?

Secondary Objective(s): If the data allows, we will evaluate the effect of
playing elite football, previous concussions and frequent heading exposure on
the prevalence of neurological and mental health issues and quality of life
(QOL). Specific secondary research questions are:
(6) Is there a difference between female retired non-contact sports athletes
and female retired football players in (a) the prevalence of
mental/neurological health issues and/or
(b) QOL?
(7) Is there a difference between female retired non-contact sports athletes
and female retired football players reporting previous concussions in (a) the
prevalence of mental/ neurological health issues and/or (b) QOL?
(8) Is there a difference between female retired non-contact sports athletes
and female retired football players reporting frequent heading exposure in (a)
the prevalence of mental/neurological health issues and/or (b) QOL?

We will conduct a case-control study design to evaluate the research questions.
One of the main short-comings in previous case-control studies on the topic is
the inclusion of inadequate control groups. To account for potential effects of
elite level exposure to exercise on brain structure and/or function, we will
compare retired female football players to a group of retired elite athletes
from non-contact sports. Further we will apply a mixed methods approach,
combining neurocognitive testing and neuroimaging modalities. This will enable
us to evaluate if subclinical abnormalities in brain networks are functionally
relevant. Additionally, a mixed methods approach will improve both the validity
and reliability of potential findings.

No known risks are associated with participation in the proposed investigation.
However, psychological discomfort may be associated with the MRI scan due to
space limitations in the scanner. Further, the NSP test battery may be
cognitively exhausting. There are several contra-indications for participation
in an MRI examination (specified above) and participants who meet these
criteria will be excluded from the study.