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Abstract
Objective: To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging.
Methods: Participants, aged 70–92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association.
Results: Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined—reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5–2.5 is approximately 15 years.
Conclusion: This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.
GLOSSARY
- AD=
- Alzheimer disease;
- ADRC=
- Mayo Alzheimer's Disease Research Center;
- CI=
- confidence interval;
- CN=
- cognitively normal;
- ICC=
- intraclass correlation;
- MCI=
- mild cognitive impairment;
- MCSA=
- Mayo Clinic Study of Aging;
- PVC=
- partial volume-corrected;
- ROI=
- region of interest;
- SUVR=
- standardized uptake values
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.
Editorial, page 878
- Received June 1, 2012.
- Accepted September 25, 2012.
- © 2013 American Academy of Neurology
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