Acute Cortisol Profile Associations With Cognitive Impairment After Severe Traumatic Brain Injury

Abstract

Background Cognitive impairments commonly occur after traumatic brain injury (TBI) and affect daily functioning. Cortisol levels, which are elevated during acute hospitalization for most individuals after severe TBI, can influence cognition, but this association has not been studied previously in TBI. Objective We hypothesized that serum and cerebral spinal fluid (CSF) cortisol trajectories over days 0–5 post-injury are associated with cognition 6-month post-injury. Methods We examined 94 participants with severe TBI, collected acute serum and/or CSF samples over days 0–5 post-injury, and compared cortisol levels to those in 17 healthy controls. N = 88 participants had serum, and n = 84 had CSF samples available for cortisol measurement and had neuropsychological testing 6 months post-injury. Group based trajectory analysis (TRAJ) was used to generate temporal serum and CSF cortisol profiles which were examined for associations with neuropsychological performance. We used linear regression to examine relationships between cortisol TRAJ groups and both overall and domain-specific cognition. Results TRAJ analysis identified a high group and a decliner group for serum and a high group and low group for CSF cortisol. Multivariable analysis showed serum cortisol TRAJ group was associated with overall cognitive composites scores ( P = .024) and with executive function ( P = .039) and verbal fluency ( P = .029) domain scores. CSF cortisol TRAJ group was associated with overall cognitive composite scores ( P = .021) and domain scores for executive function ( P = .041), verbal fluency ( P = .031), and attention ( P = .034). Conclusions High acute cortisol trajectories are associated with poorer cognition 6 months post-TBI.

APOE ε4 allele status modulates the spatial patterns of progressive atrophy in the temporal lobes after mild traumatic brain injury

“…Our results supported the idea that the interaction of AD genetic factors with mTBI leads to brain atrophy in AD‐vulnerable regions 5 . Regarding the neuropsychological signature, early lvPPA‐AD is characterized by a decline in language fluency, 36,43 which is one of the neuropsychological complaints of patients with mTBI as well 15,16 . In addition, we found that the atrophy in GM, rather than the WM, within the left superior and middle temporal gyri could predict the decline in language fluency for mTBI APOE ε4 allele carriers.…”

“…5 Regarding the neuropsychological signature, early lvPPA-AD is characterized by a decline in language fluency, 36,43 which is one of the neuropsychological complaints of patients with mTBI as well. 15,16 In addition, we found that the atrophy in GM, rather than the WM, within the left superior and middle temporal gyri could predict the decline in language fluency for mTBI APOE ε4 allele carriers. The longitudinal registration of pairs of T1 images was based on alignment between the first and second scans of each participant, in which a linear transform may be mostly influenced by the GM rather than the WM.…”

“…[12][13][14] Neuropsychological impairments post TBI contain multiple cognitive domains, which are found as in AD. 15,16 Underlying those dysfunctional phenotypes, there are distinct neuropathological hallmarks of neurodegeneration pathways in AD-vulnerable areas. The initial atrophy in either the medial or lateral temporal lobes is involved in the early stages of different AD phenotypes with typical or atypical symptoms, including the language dysfunction variant.…”

“…Recent studies have proposed that TBI increases the risk of dementia in some specific subtypes 12–14 . Neuropsychological impairments post TBI contain multiple cognitive domains, which are found as in AD 15,16 . Underlying those dysfunctional phenotypes, there are distinct neuropathological hallmarks of neurodegeneration pathways in AD‐vulnerable areas.…”

The role of the stress system in recovery after traumatic brain injury: A tribute to Bruce S. McEwen

“…While HPA axis hypoactivity is potentially dangerous, sustained hyperactivity can also lead to allostatic loading and poorer outcomes. High circulating cortisol that did not decline in the first five days after severe injury predicted poorer cognitive and overall outcomes at 6 months ( Barton et al, 2021 ; Santarsieri et al, 2014 ) although it remains unclear whether the acutely elevated glucocorticoids are imperiling recovery per se or are indicative of greater tissue damage. Thus, as predicted by allostatic theory, optimal recovery seems to occur in conditions when the HPA axis can produce sufficient physiological levels of activation but in a relatively time-limited manner.…”