Cognitive Trajectories and Associated Biomarkers in Patients with Mild Cognitive Impairment

Background: To diagnose mild cognitive impairment (MCI) patients at risk of progression to dementia is clinically important but challenging. Objective: We classified MCI patients based on cognitive trajectories and compared biomarkers among groups. Methods: This study analyzed amnestic MCI patients with at least three Clinical Dementia Rating (CDR) scores available over a minimum of 36 months from the Alzheimer's Disease Neuroimaging Initiative database. Patients were classified based on their progression using trajectory modeling with the CDR-sum of box scores. We compared clinical and neuroimaging biomarkers across groups. Results: Of 569 eligible MCI patients (age 72.7 +/- 7.4 years, women n = 223), three trajectory groups were identified: stable (58.2%), slow decliners (24.6%), and fast decliners (17.2%). In the fifth year after diagnosis, the CDR-sum of box scores increased by 1.2, 5.4, and 11.8 points for the stable, slow, and fast decliners, respectively. Biomarkers associated with cognitive decline were amyloid-beta 42, total tau, and phosphorylated tau protein in cerebrospinal fluid, hippocampal volume, cortical metabolism, and amount of cortical and subcortical amyloid deposits. Cortical metabolism and the amount of amyloid deposits were associated with the rate of cognitive decline. Conclusion: Data-driven trajectory analysis provides new insights into the various cognitive trajectories of MCI. Baseline brain metabolism, and the amount of cortical and subcortical amyloid burden can provide additional information on the rate of cognitive decline.