Objective: To investigate the relationship between Alzheimer’s disease (AD) biomarkers and cognitive change in a population of well-functioning elderly people. Methods: We followed up over 3 years 84 participants dementia-free at baseline (mean age: 72.0 years, 59% women), as part of the Harvard Aging Brain Study and the Massachusetts Alzheimer’s Disease Research Center longitudinal cohort. The relationships between baseline AD biomarkers and longitudinal cognitive change (increase of clinical dementia rating scale
[CDR] over 0, decline of Mini Mental State Examination [MMSE]) were assessed by using Cox proportional hazard regressions and linear mixed models.
Results: During the follow-up, 12 (14%) participants increased their CDR score from 0 to 0.5. Increase of CDR was associated with higher baseline CSF levels of Tau and phosphorylated Tau, brain amyloid load, and lower MRI hippocampal volume. CSF Tau was also associated with longitudinal change in MMSE score. No association was observed for CSF beta amyloid level and metabolic PET imaging. These associations remained after adjustment for age, gender, level of education, APOE ε4 status, baseline cognition, and after
the exclusion of subjects with CDR sum of boxes = 0.5 at baseline.
Conclusions: In a population of cognitively normal elderly people, AD biomarkers were associated with subtle cognitive decline, supporting the idea that biomarkers may play a role in future screening strategies.