J Neurol Neurosurg Psychiatry 74:857-862 doi:10.1136/jnnp.74.7.857
  • Paper

Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication

  1. S Fleminger1,
  2. D L Oliver1,
  3. S Lovestone2,
  4. S Rabe-Hesketh3,
  5. A Giora1
  1. 1Lishman Brain Injury Unit, Maudsley Hospital, London, UK
  2. 2Section of Old Age Psychiatry, Institute of Psychiatry, London, UK
  3. 3Department of Biostatistics and Computing, Institute of Psychiatry, London, UK
  1. Correspondence to:
 Dr S Fleminger, Consultant Neuropsychiatrist, Lishman Brain Injury Unit, Maudsley Hospital, Denmark Hill, London SE5 8AZ, UK;
  • Received 2 August 2002
  • Accepted 2 December 2002
  • Revised 26 November 2002


Objective: To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer’s disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991).

Methods: A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al.

Results: We partially replicated the results of Mortimer et al. The meta-analysis of the seven studies conducted since 1991 did not reach significance. However, analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to 2.06), indicating an excess history of head injury in those with Alzheimer’s disease. The finding of Mortimer et al that head injury is a risk factor for Alzheimer’s disease only in males was replicated. The excess risk of head injury in those with Alzheimer’s disease is only found in males (males: OR 2.29, 95% CI 1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47).

Conclusions: This study provides support for an association between a history of previous head injury and the risk of developing Alzheimer’s disease.


  • See Editorial Commentary, p 841

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