Alzheimer’s disease: reliance on biomarkers leads to overdiagnosis

  • Jack CR & al.
  • JAMA Neurol
  • 15 Jul 2019

  • International Clinical Digest
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  • Biological Alzheimer’s disease based on amyloid and tau positron emission tomography (PET) was much more prevalent than clinical Alzheimer’s disease among older adults.

Why this matters

  • With increasing use of biomarkers, definition of Alzheimer’s disease may become confusing.

Key results

  • Biological Alzheimer’s disease (abnormal amyloid and tau) was more prevalent than clinically defined probable Alzheimer’s disease for both sexes.
  • Among women (P<.001 style="list-style-type:circle;">
  • 10% vs 1% at age 70 years.
  • 33% vs 10% at age 85 years.
  • Among men (P<.001 style="list-style-type:circle;">
  • 9% vs 1% at age 70 years.
  • 31% vs 9% at age 85 years.
  • Compared with women, men had a greater prevalence of mild cognitive impairment or dementia.
  • Expert comment

    • In an editorial, Teresa Gomez-Isla, MD, PhD, and Matthew P. Frosch, MD, PhD, write, “The existence of a long clinically silent phase in AD poses a serious challenge for the design of outcome measures in prevention trials and drives up the cost and length of these trials, particularly in the absence of another surrogate marker that can be measured in vivo to estimate how far any given individual could be from theoretically entering a symptomatic phase. Subsequent future investigations must be directed to understanding the pathologic and biochemical brain changes, as well as individual genetic and epigenetic factors that, beyond just the presence of plaques and tangles, drive the clinical course in these imaging-positive individuals.”

    Study design

    • Population-based cohort study among 5213 older adults aged 60-89 years (Mayo Clinic Study of Aging) with varied clinical diagnostic entities:
      • 3926 cognitively unimpaired.
      • 640 mild cognitive impairment.
      • 647 dementia.
    • Biological diagnostic entities based on PET:
      • Alzheimer’s continuum (abnormal amyloid, regardless of tau).
      • Alzheimer’s pathologic change (abnormal amyloid, normal tau).
      • Alzheimer’s disease (abnormal amyloid and tau).
    • Main outcomes: prevalence of clinical vs biological diagnostic entities.
    • Funding: National Institutes of Health; others.


    • Fewer PET scans than intended in dementia group.
    • Unclear generalisability.
    • Inability to image individuals with severe dementia.