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Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up

  • Charlotte L. Allan (a1), Enikõ Zsoldos (a1), Nicola Filippini (a1), Claire E. Sexton (a1), Anya Topiwala (a1), Vyara Valkanova (a1), Archana Singh-Manoux (a2), Adam G. Tabák (a3), Martin J. Shipley (a4), Clare Mackay (a1), Klaus P. Ebmeier (a1) and Mika Kivimäki (a4)...



Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure.


To examine lifetime blood pressure as a predictor of brain structure in old age.


A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985–2013). In 2012–2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities.


Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy.


Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose–response pattern.


Corresponding author

Charlotte L. Allan, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. Email:


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These authors contributed equally to this work.

The Whitehall II Study is supported by grants from the Medical Research Council (K013351); British Heart Foundation; National Heart Lung and Blood Institute (R01HL036310), US National Institutes of Health (NIH); and the National Institute on Aging (R01AG013196 and R01AG034454), US NIH. The Whitehall Imaging substudy is supported by the Medical Research Council (G1001354). C.L.A has received funding for a clinical research fellowship from Oxfordshire Health Services Research Fund and from the National Institute for Health Research (NIHR); N.F. is supported by the HDH Wills 1965 Charitable Trust; C.E.S. and C.M by the NIHR Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford; M.J.S. by the British Heart Foundation; A.S.-M. by the National Institute on Aging, NIH (R01AG013196, R01AG034454); A.G.T. by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TáMOP 4.2.4. A/-11-1-2012-0001 ‘National Excellence Program’; K.P.E. by the Medical Research Council (G1001354), the HDH Wills 1965 and the Gordon Edward Small Charitable Trusts; and M.K. by the Medical Research Council (K013351), the Academy of Finland, the US NIH (R01HL036310, R01AG034454) and a professorial fellowship from the Economic and Social Research Council.

Declaration of interest

K.P.E. has received consultation fees from Lilly.



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Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up

  • Charlotte L. Allan (a1), Enikõ Zsoldos (a1), Nicola Filippini (a1), Claire E. Sexton (a1), Anya Topiwala (a1), Vyara Valkanova (a1), Archana Singh-Manoux (a2), Adam G. Tabák (a3), Martin J. Shipley (a4), Clare Mackay (a1), Klaus P. Ebmeier (a1) and Mika Kivimäki (a4)...
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