The appearance of β-amyloidosis and brain injury biomarkers in cognitively normal (CN)
persons is thought to define risk for the future development of cognitive impairment due to
Alzheimer disease (AD), but their interaction is poorly understood.
To test the hypothesis that the joint presence of β-amyloidosis and brain injury biomarkers
would lead to more rapid neurodegeneration.
Longitudinal cohort study.
Population-based Mayo Clinic Study of Aging.
One hundred ninety-one CN persons (median age, 77 years; range, 71-93 years) in the Mayo Clinic
Study of Aging who underwent magnetic resonance, fludeoxyglucose F 18 (FDG) positron emission
tomography (PET), and Pittsburgh Compound B (PiB) PET imaging at least twice 15 months apart.
Participants were grouped according to the recommendations of the National Institute on
Aging–Alzheimer Association preclinical AD criteria based on the presence of
β-amyloidosis, defined as a PiB PET standardized uptake value ratio (SUVr) greater than 1.5,
alone (stage 1) or with brain injury (stage 2 + 3), defined as hippocampal atrophy or
FDG hypometabolism. We also studied a group of patients with mild cognitive impairment
(n = 17) or dementia (n = 9) from the Mayo Clinic Study of Aging or the Mayo
Alzheimer Center with similar follow-up times who had undergone comparable imaging and had a PiB PET
SUVr greater than 1.5.
Main Outcomes and Measures
Rate of change of cortical volume on volumetric magnetic resonance images and rate of change of
glucose metabolism on FDG PET scan results.
There were 25 CN participants with both high PiB retention and low hippocampal volume or FDG
hypometabolism at baseline (preclinical AD stages 2 + 3). On follow-up scans, the
preclinical AD stage 2 + 3 participants had greater loss of medial temporal lobe volume
and greater glucose hypometabolism in the medial temporal lobe compared with the other CN groups.
The changes were similar to those in the cognitively impaired participants. Extratemporal regions
did not show similar changes.
Conclusions and Relevance
Higher rates of medial temporal neurodegeneration occur in CN individuals who, on their initial
scans, had abnormal levels of both β-amyloid and brain injury biomarkers. Although preclinical
AD is currently only a research topic, the description of its brain structural changes will be
critical for trials designed to prevent or forestall dementia due to AD.