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Neuroinflammation in long-term cognitive impairment after aneurysmal subarachnoid hemorrhage

R. Tack,N. Tolboom,Bas Meyer Viol,S. Golla,B. V. van Berckel,I. van der Schaaf,R. Boellaard,A. De Luca,M. V. van Zandvoort,J.M. Anne Visser-Meily,Elly M. Hol,G. Rinkel,M. Vergouwen

Published 2025 in International Journal of Stroke

ABSTRACT

Background: Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often have cognitive impairment, which may be caused by long-term inflammation. We aimed to determine whether long-term neuroinflammation or microstructural brain damage is associated with cognitive impairment after aSAH. Methods: In this prospective cohort study, we included patients >3 years after aSAH between 2020 and 2022. Patients underwent neuropsychological evaluation, translocator protein 18 kDA (TSPO) positron emission tomography (PET) imaging using [18F]DPA-714 to determine neuroinflammation, and brain diffusion kurtosis imaging (DKI) to determine microstructural damage. We compared TSPO PET binding potential, mean kurtosis (MK), kurtosis anisotropy (KA), axial kurtosis (AK), and radial kurtosis (RA) between groups and determined which metric was correlated with individual cognitive tests. Results: We included 27 patients with aSAH; 14 with and 13 without cognitive impairment. Whole-brain TSPO binding potential was similar between groups (mean BPND: −0.046 [95% confidence interval (CI): −0.105; 0.013] vs −0.047 [95% CI −0.108; 0.014], p = 0.98) and there were no regional differences. Those with cognitive impairment had a lower whole-brain MK (mean MK 0.70 [95% CI: 0.69-0.72] vs 0.73 [95% CI: 0.72-0.74], p = 0.03) and whole-brain AK (mean AK 0.81 [95% CI: 0.78-0.83] vs 0.86 [0.84-0.87], p = 0.04). Left thalamic MK and AK were correlated with tests of verbal memory (r = 0.60-0.67, p < 0.01), while other correlation tests were non-significant. Conclusion: Our results do not support the hypothesis that long-term cognitive impairment after aSAH is caused by long-term neuroinflammation. Instead, microstructural damage may play a role. Graphical abstract

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