Get access

Brain injury biomarkers are not dependent on β-amyloid in normal elderly

Authors

  • David S. Knopman MD,

    Corresponding author
    1. Mayo Clinic Alzheimer's Disease Research Center, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    • Department of Neurology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Clifford R. Jack Jr MD,

    1. Mayo Clinic Alzheimer's Disease Research Center, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    2. Department of Radiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Heather J. Wiste BA,

    1. Department of Health Sciences Research, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Stephen D. Weigand MS,

    1. Department of Health Sciences Research, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Prashanthi Vemuri PhD,

    1. Department of Neurology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Val J. Lowe MD,

    1. Department of Radiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Kejal Kantarci MD,

    1. Department of Radiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Jeffrey L. Gunter PhD,

    1. Department of Radiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Matthew L. Senjem MS,

    1. Department of Radiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Michelle M. Mielke PhD,

    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Rosebud O. Roberts MBBCh,

    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Bradley F. Boeve MD,

    1. Department of Neurology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    2. Mayo Clinic Alzheimer's Disease Research Center, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author
  • Ronald C. Petersen MD, PhD

    1. Department of Neurology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    2. Mayo Clinic Alzheimer's Disease Research Center, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    3. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN
    Search for more papers by this author

Address correspondence to Dr Knopman, Department of Neurology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: knopman@mayo.edu

Abstract

Objective

The new criteria for preclinical Alzheimer disease (AD) proposed 3 stages: abnormal levels of β-amyloid (stage 1), stage 1 plus evidence of brain injury (stage 2), and stage 2 plus subtle cognitive changes (stage 3). However, a large group of subjects with normal β-amyloid biomarkers have evidence of brain injury; we labeled them as the “suspected non-Alzheimer pathophysiology” (sNAP) group. The characteristics of the sNAP group are poorly understood.

Methods

Using the preclinical AD classification, 430 cognitively normal subjects from the Mayo Clinic Study of Aging who underwent brain magnetic resonance (MR), 18fluorodeoxyglucose (FDG), and Pittsburgh compound B positron emission tomography (PET) were evaluated for FDG PET regional volumetrics, MR regional brain volumetrics, white matter hyperintensity volume, and number of infarcts. We examined cross-sectional associations across AD preclinical stages, those with all biomarkers normal, and the sNAP group.

Results

The sNAP group had a lower proportion (14%) with apolipoprotein E ε4 genotype than the preclinical AD stages 2 + 3. The sNAP group did not show any group differences compared to stages 2 + 3 of the preclinical AD group on measures of FDG PET regional hypometabolism, MR regional brain volume loss, cerebrovascular imaging lesions, vascular risk factors, imaging changes associated with α-synucleinopathy, or physical findings of parkinsonism.

Interpretation

Cognitively normal persons with brain injury biomarker abnormalities, with or without abnormal levels of β-amyloid, were indistinguishable on a variety of imaging markers, clinical features, and risk factors. The initial appearance of brain injury biomarkers that occurs in cognitively normal persons with preclinical AD may not depend on β-amyloidosis. ANN NEUROL 2013;73:472–480

Get access to the full text of this article

Ancillary