Usefulness of CSF Biomarkers in Predicting the Progression of Amnesic and Nonamnesic Mild Cognitive Impairment to Alzheimer’s Disease

摘要

Objective: The aim of this study was to investigate the usefulness of Alzheimer’s diseaseCerebrospinal Fluid (CSF) biomarkers in predicting the progression to dementia in patients withMild Cognitive Impairment (MCI).Methods: One hundred and thirteen patients were consecutively recruited from April 2012 to April2014. Measurement of CSF biomarkers (amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylatedtau (p-tau)) and a neuropsychological evaluation were performed for all patients. We categorizedpatients with MCI as A+A- and N+N- based on the presence/absence of amyloid pathology andneurodegeneration, respectively.Results: Of 72 patients with MCI, 26 (36%) progressed to dementia. These patients had lower CSFAβ42 levels and higher p-tau and t-tau levels at baseline. The proportion that progressed to dementiawas 14.3% (2/14), 36.8% (7/19), 66.7% (4/6) and 75% (12/16) in the A-N-, A+N-, A-N+(SNAP), and A+N+ patients, respectively (p < 0.05). There were significant differences in theprobability of progression from amnestic MCI (aMCI) to AD between the A+N+ and A-N- patients(OR = 8.1, 95% CI 1.5-42.3, p = 0.001) but not between SNAP (OR = 7.3, 95% CI 0.9-61, p =0.02) or A+N- (OR = 2.1, 95% CI 0.4 to 10.4, p = 0.15) patients compared to the A-N- subgroup.None of the biomarker profiles of the subgroups predicted the time until the progression to AD.Conclusion: The use of CSF AD biomarkers in clinical practice improves the certainty of diagnosisand prognosis of patients, especially in patients in the prodromal phase or in patients with atypicalpresentations.