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Cognitive function in adolescence and the risk of early-onset stroke
  1. Aya Bardugo1,2,3,4,
  2. Cole D Bendor1,2,3,5,
  3. Carmit Libruder6,
  4. Miri Lutski4,6,
  5. Inbar Zucker4,6,
  6. Avishai M Tsur1,2,3,5,7,
  7. Estela Derazne4,
  8. Gal Yaniv4,8,
  9. Raquel C Gardner9,
  10. Hertzel C Gerstein10,
  11. Tali Cukierman-Yaffe5,11,
  12. Yael Lebenthal4,12,
  13. David Batty13,
  14. David Tanne14,
  15. Ariel Furer1,2,
  16. Arnon Afek15,
  17. Gilad Twig3,5,11
  1. 1 Department of Military Medicine, Hebrew University, Jerusalem, Israel
  2. 2 Israel Defense Forces Medical Corps, Ramat Gan, Israel
  3. 3 The Gertner Institute for Epidemiology & Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
  4. 4 Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  5. 5 Department of Preventive Medicine and Epidemiology, School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  6. 6 Israel Center for Disease Control, State of Israel Ministry of Health, Ramat Gan, Israel
  7. 7 Department of Medicine, Sheba Medical Center, Tel Hashomer, Israel
  8. 8 Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel
  9. 9 The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel
  10. 10 Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  11. 11 Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Tel Hashomer, Israel
  12. 12 The Institute of Pediatric Endocrinology, Diabetes and Metabolism, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  13. 13 Department of Epidemiology and Public Health, University College London, London, UK
  14. 14 Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa, Israel
  15. 15 Reichman University, Herzelia, Israel
  1. Correspondence to Professor Gilad Twig, The Gertner Institute for Epidemiology and Health Policy, Sheba Medical Center, Ramat Gan, Israel; Gilad.Twig{at}


Background Stroke is increasingly prevalent at younger ages but the risk factors are uncertain. We examined the association between adolescent cognitive function and early-onset stroke.

Methods This was a nationwide population-based cohort study of 1 741 345 Israeli adolescents (42% women) who underwent comprehensive cognitive function tests at age 16–20 years, before mandatory military service, during 1987–2012. Cognitive function (range: 1–9) was categorised as low (1–3, corresponding to IQ score below 89), medium (4–7, IQ score range: 89–118), or high (8–9, IQ score above 118). Participant data were linked to the Israeli National Stroke Registry. Cox proportional hazard models were used to estimate risks for the first occurrence of ischaemic stroke during 2014–2018.

Results During 8 689 329 person-years of follow-up, up to a maximum age of 50 years, 908 first stroke events occurred (767 ischaemic and 141 haemorrhagic). Compared with a reference group of people with high cognitive function, body mass index-adjusted and sociodemographic-adjusted HRs (95% CIs) for early-onset stroke were 1.78 (1.33–2.38) in medium and 2.68 (1.96–3.67) in low cognitive function groups. There was evidence of a dose–response relationship (P for trend <0.0001) such that one-unit of lower cognitive function z-score was associated with a 33% increased risk of stroke (1.33; 1.23–1.42). These associations were similar for ischaemic stroke but lower for haemorrhagic stroke; persisted in sensitivity analyses that accounted for diabetes status and hypertension; and were evident before age 40 years.

Conclusions Alongside adolescent obesity and hypertension, lower cognitive function may be a risk factor for early-onset stroke.

  • stroke
  • adolescent
  • cognition

Data availability statement

Data are available upon reasonable request. The data are not publicly available due to governmental and ethical restrictions. Interested parties can contact the corresponding author via email.

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Data availability statement

Data are available upon reasonable request. The data are not publicly available due to governmental and ethical restrictions. Interested parties can contact the corresponding author via email.

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  • Contributors AB and CDB wrote the original draft. AB, CDB, ED and GT performed the formal analysis. AB, CDB and GT conceptualised the study, designed the methodology and directly accessed and verified the underlying data reported in the manuscript. CL, ML, IZ, AMT, GY, RCG, HG, TC-Y, YL, DB, DT, AF and AA reviewed and edited the manuscript. GT supervised the study. GT is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.