The relevance of cognitive reserve for the investigation of prognostic factors after acquired brain injury

<p dir="ltr">Acquired brain injury (ABI) is a leading cause of long-term disability worldwide. Traumatic brain injury (TBI) and stroke are the two most common causes of ABI. Both TBI and stroke vary in severity, with TBI often being classified as mild, moderate and severe TBI. Long-term outcomes after ABI are complex, often involving multiple areas of life and being influenced by various factors. Cognitive reserve, the brain's capacity to mitigate the impact of pathology or injury on clinical outcomes, has been identified as a factor explaining some of the variability in outcomes following ABI. Although cognitive reserve cannot be directly measured, it is typically estimated through indicators such as educational attainment or assessments of premorbid cognitive functioning. Despite its significance, many aspects of cognitive reserve remain unresolved. This thesis explores various outcomes post-ABI and examines the influence of cognitive reserve on these outcomes.</p><p dir="ltr">The first paper investigated the relationship between cognitive functioning 3 months after injury and long-term outcome measured by the Mayo-Portland Adaptability Index (MPAI-4) in 41 patients with severe TBI (sTBI) 6-8 years after injury. The result from an early cognitive screening was related to long-term participation, ability and adaption according to the MPAI-4 after sTBI. However different neuropsychological tests appeared to measure complementary aspects of outcomes. Furthermore, as early as three months after sTBI, educational level affected scores on neuropsychological screening instruments, suggesting a ceiling effect for individuals with higher education levels, which may mask cognitive deficits.</p><p dir="ltr">The second paper examined differences in symptoms after mild TBI (mTBI), symptom resolution, and functional connectivity between 15 patients with mTBI and 15 with minor orthopedic injuries at one week and three months post-injury. Assessments comprised of neuropsychological tests including a test of premorbid intelligence, resting state functional magnetic resonance imaging (rs- fMRI) scans, and symptom ratings. One-week post-injury, the mTBI group had significantly higher post-concussion symptoms, state fatigue, and fatigability compared to controls. After three months, the patients with mTBI still scored higher post-concussion symptoms but had returned to the same level as the controls regarding fatigability. Functional connectivity differences between groups in the frontoparietal network were noted. Improvement in post-concussion symptoms was related to cognitive reserve, measured with educational level but not with results on a test of premorbid intelligence, in the mTBI group.</p><p dir="ltr">In the third and fourth papers 83 patients with TBI or stroke, who had undergone specialized brain injury rehabilitation, were interviewed 5-15 years after brain injury. The third paper explored how cognitive reserve (measured by education) and neuropsychological test results affect return-to-work and life satisfaction after ABI. Higher return-to-work rates were linked to higher cognitive reserve, lower age, less fatigue, and better working memory and processing speed. Less fatigue was associated with better satisfaction with mental health, but no other variables significantly impacted aspects of life satisfaction. Verbal and spatial abilities were related to education but not to return-to-work.</p><p dir="ltr">The fourth paper investigated differences in healthcare usage based on cognitive reserve and its relationship to outcomes following stroke and TBI. It found that individuals with higher education levels utilized more healthcare services in the year of injury, even after adjusting for confounding variables such as injury severity. This increased healthcare usage was significantly associated with better long-term life satisfaction, although it did not correlate with a higher likelihood of returning to work.</p><p dir="ltr">In summary, the studies in this thesis confirm the complex link between cognitive reserve and brain injury outcomes. Higher education levels generally correlate with better outcomes, particularly for return-to-work rather than life satisfaction. Some of the positive effects of cognitive reserve may also result from other factors such as ceiling effects in cognitive tests or better rehabilitation access for more educated individuals.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Ekdahl N,</b> Godbolt AK, Deboussard CN, Lannsjö M, Stålnacke BM, Stenberg M, et al. Cognitive Reserve, Early Cognitive Screening, and Relationship to Long-Term Outcome after Severe Traumatic Brain Injury. J Clin Med. 2022;11(7). <a href="https://doi.org/10.3390/jcm11072046" rel="noreferrer" target="_blank">https://doi.org/10.3390/jcm11072046</a></p><p dir="ltr">II. <b>Ekdahl N,</b> Möller MC, Deboussard CN, Stålnacke BM, Lannsjö M, Nordin LE. Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury. BMC Neurol. 2023;23(1):450. <a href="https://doi.org/10.1186/s12883-023-03509-8" rel="noreferrer" target="_blank">https://doi.org/10.1186/s12883-023-03509-8</a></p><p dir="ltr">III. <b>Ekdahl N,</b> Lannsjö M, Stålnacke BM, Möller MC. The relationship between cognitive reserve, cognitive performance and outcomes of return to work and life satisfaction after brain injury: A retrospective cohort study. Disability and Rehabilitation. 2025;16:1-11. <a href="https://doi.org/10.1080/09638288.2025.2517240" rel="noreferrer" target="_blank">https://doi.org/10.1080/09638288.2025.2517240</a></p><p dir="ltr">IV. <b>Ekdahl N,</b> Lannsjö M, Stålnacke BM, Möller MC. Cognitive Reserve and Disparities in Healthcare Usage after Traumatic Brain Injury and Stroke: An Observational Cohort study. Journal of Rehabilitation Medicine. 2025; 57. <a href="https://doi.org/10.2340/jrm.v57.42400" rel="noreferrer" target="_blank">https://doi.org/10.2340/jrm.v57.42400</a></p>