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Biomarkers and the diagnosis of preclinical dementia

  • Philippa Lilford (a1) and Julian C. Hughes (a2)

Alzheimer's disease pathology accumulates years before the onset of clinical symptoms and has been termed ‘preclinical dementia’. Biomarkers have been developed to detect this pathology – namely, brain amyloid deposition and markers of neurodegeneration. In this article we describe these biomarkers and review the evidence for their clinical use in predicting risk both in the cognitively ‘normal’ and in those who already have established cognitive decline. We also discuss the limitations and ethical considerations of these tests and consider whether we should start incorporating Alzheimer's disease biomarkers into clinical practice. We find that, because many cognitively healthy people will have Alzheimer's pathology, and it is not clear whether this does help predict future risk of Alzheimer's disease, diagnosing preclinical dementia carries numerous ethical implications and is currently not being advocated outside research settings.


  • Understand the concepts of preclinical and prodromal Alzheimer's disease and the use of biomarkers in this context
  • Analyse the supporting evidence for the use of biomarkers in prodromal and preclinical dementia
  • Apply this information to everyday clinical practice


J. C. H. works in the Research Institute for the Care of Older People (RICE), which undertakes clinical drug trials for drug companies. He is a sub-investigator on a number of trials (some of which involve neuroimaging and biomarkers) and principal investigator and chief investigator on two trials (neither of which involves biomarkers). All of these trials concern Alzheimer's disease or dementia. He does not receive any direct personal payment from the trials: the payment goes to RICE, which does, however, fund almost half of his post. RICE is an independent charity and separate from the University of Bristol.

Corresponding author
Correspondence Professor Julian C. Hughes, The RICE Centre, Building 8, Royal United Hospital, Combe Park, Bath BA1 3NG, UK. Email:
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Biomarkers and the diagnosis of preclinical dementia

  • Philippa Lilford (a1) and Julian C. Hughes (a2)
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