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Abstract
Objective To examine the feasibility of using cross-sectional PET to identify cognitive decliners among β-amyloid (Aβ)-negative cognitively normal (CN) elderly adults.
Methods We determined the highest Aβ-affected region by ranking baseline and accumulation rates of florbetapir-PET regions in 355 CN elderly adults using 18F-florbetapir-PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The banks of the superior temporal sulcus (BANKSSTS) were found as the highest Aβ-affected region, and Aβ positivity in this region was defined as above the lowest boundary of BANKSSTS standardized uptake value ratio of Aβ+ (ADNI-defined COMPOSITE region) CN individuals. The entire CN cohort was divided as follows: stage 0, BANKSSTS−COMPOSITE−; stage 1, BANKSSTS+COMPOSITE−; and stage 2, BANKSSTS+COMPOSITE+. Linear mixed-effect (LME) models investigated subsequent longitudinal cognitive change, and 18F-flortaucipir (FTP)-PET was measured 4.8 ± 1.6 years later to track tau deposition.
Results LME analysis revealed that individuals in stage 1 (n = 64) and stage 2 (n = 99) showed 2.5 (p < 0.05) and 4.8 (p < 0.001) times faster memory decline, respectively, than those in stage 0 (n = 191) over >4 years of mean follow-up. Compared to stage 0, both stage 1 (p < 0.05) and stage 2 (p < 0.001) predicted higher FTP in entorhinal cortex.
Conclusions Nominally Aβ− CN individuals with high Aβ in BANKSSTS are at increased risk of cognitive decline, probably showing an earlier stage of Aβ deposition. Our findings may help elucidate the association between brain Aβ accumulation and cognition in Aβ− CN cohorts.
Classification of evidence This study provides Class II evidence that in elderly CN individuals those with high PET-identified superior temporal sulcus Aβ burden have an increased risk of cognitive decline.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- BANKSSTS=
- banks of the superior temporal sulcus;
- CN=
- cognitively normal;
- FDG=
- 18F-fluorodeoxyglucose;
- FTP=
- 18F-flortaucipir;
- GLM=
- generalized linear models;
- GMM=
- gaussian mixed-model;
- LME=
- linear mixed-effect;
- p-tau=
- phosphorylated tau;
- PCC=
- posterior cingulate cortex;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio;
- t-tau=
- total tau
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 in the coinvestigators list at links.lww.com/WNL/B81.
Editorial, page 603
Class of Evidence: NPub.org/coe
- Received April 29, 2019.
- Accepted in final form November 14, 2019.
- © 2020 American Academy of Neurology
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