A Nomogram for Predicting Amyloid PET Positivity in Amnestic Mild Cognitive Impairment

Abstract

Background: Most clinical trials focus on amyloid-beta positive (A beta+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on A beta PET. Therefore, it becomes necessary for clinicians to predict which patients will have A beta biomarker. Objective: We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE) genotype between A beta+ aMCI and A beta- aMCI and to develop a clinically useful prediction model of A beta positivity on PET (PET-A beta) in aMCI using a nomogram. Methods: We recruited 523 aMCI patients who underwent A beta PET imaging in a nation-wide multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-A beta+ in aMCI patients was constructed using a logistic regression model. Results: PET-A beta+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p= 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p =0.001). Also, presence of APOE epsilon 4 (OR 4.14, p <0.001) was associated with PET-A beta+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation. Conclusions: The nomogram consisting of NP profiles, especially memory domain, and APOE epsilon 4 genotype may provide a useful predictive model of PET-A beta+ in patients with aMCI.