Predicting amyloid-PET positivity and clinical conversion in APOE ε3/ε3
non-demented individuals with multimodal factors
Abstract
The most typical pathological change in Alzheimer’s disease (AD) is the
aggregated deposition of amyloid-β (Aβ). APOE ε3/ε3 is the most
prevalent genotype in the AD population. Individuals with amyloid-PET
(Aβ-PET) positivity (+) and disease progression may not be a minority in
the APOE ε3/ε3 non-demented population. This study searched for
accessible and available clinical models that can predict Aβ-PET (+),
and assess factors that can predict clinical conversion in APOE ε3/ε3
non-demented individuals. We selected 293 non-demented individuals with
APOE ε3/ε3 from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
database. They were divided into Aβ-PET (+) and Aβ-PET (-) groups based
on the 18F-florbetapir PET SUVR cut-off value of >1.11.
Stepwise regression and the receiver operating characteristic curve
(ROC) were used to search for a single or a combination of clinical
variables, and to assess the accuracy of clinical markers, respectively.
The Cox regression model was used to explore the risk factors associated
with clinical transition. Our study found that the combination of
clinical markers (Model A4: sex, education, ventricle and WMH volume;
Model D5: everyday cognition study-partner total (EcogSPTotal) score,
age, plasma p-tau 181 and WMH) respectively predicted Aβ-PET status in
cognitively normal (CN) individuals and mild cognitive impairment (MCI)
individuals. Aβ-PET (+) and EcogSPTotal score were independent
predictors of clinical transition in APOE ε3/ε3 non-demented
individuals. These specific factors offered an attractive and
cost-effective assessment for Aβ status and clinical conversion.