Selective Worsening of Brain Injury Biomarker Abnormalities in Cognitively Normal Elderly Persons With β-Amyloidosis
Open accessAbstract
IMPORTANCE: 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. OBJECTIVE: To test the hypothesis that the joint presence of β-amyloidosis and brain injury biomarkers would lead to more rapid neurodegeneration. DESIGN Longitudinal cohort study. SETTING: Population-based Mayo Clinic Study of Aging. PARTICIPANTS: 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. 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.
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- Authors
- Knopman, D. S., Jack, C. R., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V. J., Kantarci, K., Gunter, J. L., Senjem, M. L., Mielke, M. M., Roberts, R. O., Boeve, B. F., & Petersen, R. C.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Knopman, David S.
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2013-08-01
- Volume
- 70
- Issue
- 8
- Pages
- 1030
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC3884555
- OpenAlex
- W1987064062
- Cited by
- 68
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 9 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 13 · 2013: 4
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (U01AG006786, R01AG011378, R01AG041851, P50AG016574)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- preclinical Alzheimer's disease, beta-amyloidosis, brain injury biomarkers, hippocampal atrophy, neurodegeneration, medial temporal lobe, Pittsburgh compound B PET, FDG-PET, mild cognitive impairment, dementia, Mayo Clinic Study of Aging, Alzheimer's disease risk
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloidosis, Atrophy, Female, Hippocampus, Humans, Longitudinal Studies, Male, Risk, Temporal Lobe, Biomarkers, Amyloid beta-Peptides, Cognitive Dysfunction, Prodromal Symptoms
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