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Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study

BMJ 2017; 357 doi: (Published 06 June 2017) Cite this as: BMJ 2017;357:j2353
  1. Anya Topiwala, clinical lecturer in old age psychiatry1,
  2. Charlotte L Allan, academic clinical lecturer in old age psychiatry1,
  3. Vyara Valkanova, specialist registrar in old age psychiatry1,
  4. Enikő Zsoldos, postdoctoral scientist1,
  5. Nicola Filippini, postdoctoral scientist1,
  6. Claire Sexton, postdoctoral scientist2,
  7. Abda Mahmood, research assistant1,
  8. Peggy Fooks, medical student3,
  9. Archana Singh-Manoux, professor of epidemiology and public health4,
  10. Clare E Mackay, associate professor1,
  11. Mika Kivimäki, professor4,
  12. Klaus P Ebmeier, professor of old age psychiatry1
  1. 1Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK
  2. 2FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK
  3. 3University of Oxford, Warneford Hospital, Oxford, OX3 9DU, UK
  4. 4Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK
  1. Correspondence to: A Topiwala anya.topiwala{at}
  • Accepted 11 May 2017


Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.

Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).

Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).

Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.

Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.

Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.

Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.


  • We thank the Whitehall II cohort participants for their time and D Lunn for statistical advice to the corresponding author.

  • Contributors: AT and CLA planned the study and acquired and analysed data. VV and PF analysed data. EZ and AM acquired data. NF and CS acquired and analysed data. AS-M, CEM, and MK also planned the study. KPE planned the study and analysed data. All authors contributed towards writing the paper. AT, KPE, and MK are guarantors.

  • Funding: The study was funded by UK Medical Research Council (G1001354; KPE), the Gordon Edward Small’s Charitable Trust (SC008962; KPE), and the HDH Wills 1965 charitable trust (charity No: 1117747; KPE). MK was supported by the Medical Research Council (K013351) and NordForsk.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: grant support for the submitted work is detailed above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved as part of a larger study (Predicting MRI abnormalities with longitudinal data of the Whitehall II sub- study; MSD/IDREC/C1/2011/71) by the University of Oxford medical sciences interdivisional research ethics committee.

  • Data sharing: Policy referenced on: Data will be shared a period of two years after collection to allow the research group and collaborators time for analysis and publication. Reference to Whitehall II Data sharing policy here:

  • Transparency: The lead authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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