Abstract
Objective: To test the hypotheses predicted in a hypothetical model of Alzheimer disease (AD) biomarkers that rates of β-amyloid (Aβ) accumulation on PET imaging are not related to hippocampal neurodegeneration whereas rates of neurodegenerative brain atrophy depend on the presence of both amyloid and neurodegeneration in a population-based sample.
Methods: A total of 252 cognitively normal (CN) participants from the Mayo Clinic Study of Aging had 2 or more serial visits with both amyloid PET and MRI. Subjects were classified into 4 groups based on baseline positive/negative amyloid PET (A+ or A−) and baseline hippocampal volume (N+ or N−). We compared rates of amyloid accumulation and rates of brain atrophy among the 4 groups.
Results: At baseline, 148 (59%) were amyloid negative and neurodegeneration negative (A−N−), 29 (12%) amyloid negative and neurodegeneration positive (A−N+), 56 (22%) amyloid positive and neurodegeneration negative (A+N−), and 19 (8%) amyloid positive and neurodegeneration positive (A+N+). High rates of Aβ accumulation were found in those with abnormal amyloid at baseline and were not influenced by hippocampal neurodegeneration at baseline. In contrast, rates of brain atrophy were greatest in A+N+.
Conclusions: We describe a 2-feature biomarker approach to classifying elderly CN subjects that is complementary to the National Institute on Aging–Alzheimer's Association preclinical staging criteria. Our results support 2 key concepts in a model of the temporal evolution of AD biomarkers. First, the rate of Aβ accumulation is not influenced by neurodegeneration and thus may be a biologically independent process. Second, Aβ pathophysiology increases or catalyzes neurodegeneration.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- CN=
- cognitively normal;
- FDG=
- fluorodeoxyglucose;
- HVa=
- total intracranial volume–adjusted hippocampal volume;
- MCI=
- mild cognitive impairment;
- MCSA=
- Mayo Clinic Study of Aging;
- MPRAGE=
- magnetization-prepared rapid gradient echo;
- NFT=
- neurofibrillary tangle;
- NIA-AA=
- National Institute on Aging–Alzheimer's Association;
- ROI=
- region of interest;
- SNAP=
- suspected non-Alzheimer pathophysiology;
- SUVR=
- standardized uptake value ratio;
- TIV=
- total intracranial volume
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by NIH RO1 AG041851.
Editorial, page 1576
- Received September 3, 2013.
- Accepted in final form January 7, 2014.
- © 2014 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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