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Neurodegenerative cerebrospinal fluid biomarkers tau and amyloid beta predict functional, quality of life, and neuropsychological outcomes after aneurysmal subarachnoid hemorrhage

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Abstract

Cerebrospinal fluid (CSF) biomarkers might be useful in predicting outcome after aneurysmal subarachnoid hemorrhage (aSAH). It was the aim to determine whether tau and amyloid beta CSF concentrations predict functional, health-related quality of life (hrQoL), and neuropsychological outcomes after aSAH. Ventricular CSF was obtained from n = 24 aSAH patients at admission (D0), day 2 (D2), and day 6 (D6). CSF total (t)Tau, phosphorylated (p)Tau(181P), and amyloid beta(1-40 and 1-42) (Aβ40/Aβ42) levels were compared between patients with favorable and unfavorable functional (modified Rankin Scale (mRS)), hrQoL (Euro-Qol (EQ-5D)), and neuropsychological outcomes at 3 (3 m) and 12 months (12 m). Patients with unfavorable functional (mRS 4–6) and hrQoL outcome (EQ-5D z-score ≤ − 1.0) at 3 and 12 m had higher CSF tTau/pTau and lower Aβ40/Aβ42 at D0, D2, and D6 with varying degrees of statistical significance. In terms of predicting neuropsychological outcome, CSF pTau showed a statistically significant correlation with the z-scores of executive function (r = − 0.7486, p = 0.008), verbal memory (r = − 0.8101, p = 0.002), attention (r = − 0.6498, p = 0.030), and visuospatial functioning (r = − 0.6944, p = 0.017) at 3 m. At 12 m, CSF pTau had statistically significant correlations with the z-scores of verbal memory (r = − 0.7473, p = 0.008) and visuospatial functioning (r = − 0.6678, p = 0.024). In conclusion, higher tTau/pTau and lower Aβ40/Aβ42 CSF levels predict unfavorable long-term functional and hrQoL outcomes. Neuropsychological deficits correlate with increased CSF tTau and pTau concentrations.

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Acknowledgements

The authors thank Cornelia Lüthi (study nurse) for her excellent follow-up questionnaires management and Carolin Hock and Jessica Reid for proofreading the manuscript. We also thank Franziska Löhrer, Brigitte Rechsteiner, and Rita Bischof for performing the ELISAs.

Funding

CSF protein ELISA test kits were provided by Fujirebio Europe N.V. (Ghent, Belgium). The funding source did not influence the data collection, measurements, interpretation, or drafting of the manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Holger Joswig, Lorenz Epprecht, Gerhard Hildebrandt, Jean-Yves Fournier & Martin Nikolaus Stienen

  2. Department of Clinical Neurological Sciences, Division of Neurosurgery, London Health Sciences Centre, University Hospital, London, ON, Canada

    Holger Joswig

  3. Center for Laboratory Medicine, St. Gallen, Switzerland

    Wolfgang Korte

  4. Department of Neurology, Division of Neuropsychology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

    Severin Früh

  5. Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland

    Martin Nikolaus Stienen

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  1. Holger Joswig
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  2. Wolfgang Korte
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  4. Lorenz Epprecht
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  7. Martin Nikolaus Stienen
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Correspondence to Holger Joswig.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee St. Gallen, Switzerland (EKSG 13/011/1B). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was registered at ClinicalTrials.gov (Identifier: NCT02129010; URL https://clinicaltrials.gov/ct2/show/NCT02129010).

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Informed consent was obtained from all individual participants or his/her next of kin or substitute decision maker.

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Supplementary Table 1

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Supplementary Figure 1

Cerebrospinal fluid (CSF) measurements of total Tau (tTau; A), phosphorylated Tau (pTau; B), Amyloid beta 40 (Aβ40; C) and 42 (Aβ42; D) at admission day (D0), day 2 (D2) and day 6 (D6) after aneurysmal hemorrhage in patients with favorable (Montreal Cognitive Assessment (MoCA) score ≥ 26) and unfavorable neuropsychological screening results (MoCA <26) at three (3 m; blue circles) and 12 months (12 m; gray squares). Results are presented in mean pg/ml and standard error of mean (SEM). * = p < 0.05; + = p < 0.10. (JPEG 2161 kb)

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Joswig, H., Korte, W., Früh, S. et al. Neurodegenerative cerebrospinal fluid biomarkers tau and amyloid beta predict functional, quality of life, and neuropsychological outcomes after aneurysmal subarachnoid hemorrhage. Neurosurg Rev 41, 605–614 (2018). https://doi.org/10.1007/s10143-017-0900-6

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