Comparing predictors of conversion and decline in mild cognitive impairment

TLDR

The study aimed to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements in patients with amnestic mild cognitive impairment to identify optimal markers for predicting disease progression. Baseline APOE ε4 status, CSF Aβ1‑42, total tau, p‑tau181p, FDG‑PET glucose metabolism, hippocampal volume, and episodic memory were measured in 85 amnestic MCI participants from ADNI, with each variable dichotomized by external cutoffs and used to predict conversion to Alzheimer disease and cognitive decline over an average of 1.9 years. Patients with abnormal FDG‑PET and episodic memory were 11.7 times more likely to convert to Alzheimer disease, while the CSF p‑tau181p/Aβ1‑42 ratio and, marginally, FDG‑PET predicted cognitive decline, indicating that baseline FDG‑PET and episodic memory best predict conversion whereas the CSF ratio best predicts longitudinal decline.

Abstract

<b>Objective:</b> A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. <b>Methods:</b><i>APOE</i> ε4 allele frequency, CSF proteins (Aβ_1-42, total tau, hyperphosphorylated tau [p-tau_181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer9s Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer9s Disease Assessment Scale–Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). <b>Results:</b> Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (<i>p</i> ≤ 0.02). In addition, the CSF ratio p-tau_181p/Aβ_1-42 (β = 1.10 ± 0.53; <i>p</i> = 0.04) and, marginally, FDG-PET predicted cognitive decline. <b>Conclusions:</b> Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau_181p/Aβ_1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.