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Abstract
Objective To understand the time course of β-amyloid (Aβ) deposition in the brain, which is crucial for planning therapeutic trials of Aβ-lowering therapies in Alzheimer disease (AD).
Methods Two samples of participants from the Alzheimer's Disease Neuroimaging Initiative were studied with [18F]Florbetapir (FBP) Aβ PET and followed for up to 9 years. Sample A included 475 cognitively normal (CN) older people and those with mild cognitive impairment (MCI) and AD and sample B included 220 CN Aβ− individuals. We examined the trajectory of FBP over time in sample A and the incidence rate of conversion from negative to positive Aβ PET scans in sample B.
Results The relationship between time and brain Aβ was sigmoidal, taking 6.4 years to transition from amyloid negative to positive and another 13.9 years to the onset of MCI. Aβ deposition rates began to slow only 3.8 years after reaching the positivity threshold. The incidence rate for scan positivity was 38/1,000 person-years, and factors associated with conversion were age, baseline FBP, and being a female APOE ε4 carrier. Among CN Aβ− individuals, FBP slopes were associated with rates of memory decline and brain tau measured with [18F]Flortaucipir PET 5 years after baseline.
Conclusions Lowering brain Aβ must be accomplished early in the evolution of AD. Transitions of PET scans from Aβ− to Aβ+ should be predictable, and it is reasonable to expect that lowering rates of Aβ even in early stages could produce clinically significant benefits.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- CN=
- cognitively normal;
- FBP=
- [18F]florbetapir;
- FTP=
- [18F]flortaucipir;
- FWHM=
- full width at half maximum;
- MCI=
- mild cognitive impairment;
- ROI=
- region of interest;
- SMC=
- subjective memory complaints;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at links.lww.com/WNL/B308.
- Received July 7, 2020.
- Accepted in final form October 28, 2020.
- © 2021 American Academy of Neurology
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