A multi‐cohort study of longitudinal and cross‐sectional Alzheimer's disease biomarkers in cognitively unimpaired older adults
Long Xie, Sandhitsu R. Das, Yue Li, Laura E.M. Wisse, Emily McGrew, Xueying Lyu, Michael DiCalogero, Ujashi Shah, Ademola Ilesanmi, Amanda E Denning, Christopher Brown, Jesse Cohen, Lasya P Sreepada, Mengjin Dong, Niyousha Sadeghpour, Pulkit Khandelwal, Ranjit Ittyerah, Sadhana Ravikumar, Shokufeh Sadaghiani, Stanislau Hrybouski, Robin de Florès, Eli Gibson, Paul A. Yushkevich, S. J. Wolk, for the Alzheimer's Disease Neuroimaging Initiative
Abstract
INTRODUCTION: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear. METHOD: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A-/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted. Cross-sectional MTL tau burden (T) was computed from tau positron emission tomography (N = 1095). RESULTS: We found cross-sectional tau and longitudinal structural biomarkers best separated A+ CU from A- CU. A-T+ CU had significantly faster neurodegeneration rate compared to A-T- CU. MTL tau was significantly correlated with MRI and cognitive biomarkers regardless of Aβ status. MTL tau, MRI, and cognition provided complementary information about disease progression. DISCUSSION: This large multisite study replicates prior findings in CU older adults, supporting the utility of neuroimaging and cognitive biomarkers in preclinical AD clinical trials and normal aging studies. HIGHLIGHTS: We investigated neuroimaging and cognitive biomarkers in 3036 cognitively unimpaired (CU) participants. Medial temporal lobe (MTL) tau and longitudinal MTL atrophy best separate amyloid beta positive (A+) CU from amyloid beta negative (A-) CU. A- tau positive (T+) CU had a significantly faster neurodegeneration rate compared to A-T- CU. MTL tau correlated with structural magnetic resonance imaging (MRI) and cognition regardless of amyloid beta status. Combined baseline MTL tau, MRI, and cognition best predict Alzheimer's disease progression.