Predicting amyloid-PET and clinical conversion in apolipoprotein E ε3/ε3 non-demented individuals with multidimensional factors

The apolipoprotein E (APOE) epsilon 4 is a well-established risk factor of amyloid-beta (A beta) in Alzheimer's disease (AD). However, because of the high prevalence of APOE epsilon 3, there may be a large number of people with APOE epsilon 3/epsilon 3 who are non-demented and have A beta pathology. There are limited studies on assessing A beta status and clinical conversion in the APOE epsilon 3/epsilon 3 non-demented population. Two hundred and ninety-three non-demented individuals with APOE epsilon 3/epsilon 3 from ADNI database were divided into A beta-positron emission tomography (A beta-PET) positivity (+) and A beta-PET negativity (-) groups using cut-off value of >1.11. Stepwise regression searched for a single or multidimensional clinical variables for predicting A beta-PET (+), and the receiver operating characteristic curve (ROC) assessed the accuracy of the predictive models. The Cox regression model explored the risk factors associated with clinical conversion to mild cognitive impairment (MCI) or AD. The results showed that the combination of sex, education, ventricle and white matter hyperintensity (WMH) volume can accurately predict A beta-PET status in cognitively normal (CN), and the combination of everyday cognition study partner total (EcogSPTotal) score, age, plasma p-tau 181 and WMH can accurately predict A beta-PET status in MCI individuals. EcogSPTotal score were independent predictors of clinical conversion to MCI or AD. The findings may provide a non-invasive and effective tool to improve the efficiency of screening A beta-PET (+), accelerate and reduce costs of AD trial recruitment in future secondary prevention trials or help to select patients at high risk of disease progression in clinical trials.