Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease

Background: We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD). Methods: We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (A beta 1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132). Results: CSF A beta 1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage. Conclusion: This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.