Cerebrospinal fluid (CSF), positron emission tomography (PET) and magnetic resonance imaging (MRI) serve as three important tools to track biological changes in AD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) provides the infrastructure for investigators to examine the longitudinal patterns of CSF, PET and MRI biomarkers at different cognitive stages. We delineated the biomarker changes over time in relation to cognitive decline in ADNI and found that the trajectories support a hypothetical sequence of AD pathology, suggesting that biomarker prediction for cognitive change is stage dependent.
Cognitive reserve has been proposed to account for the discordance between cognitive performance and AD pathology. The long held viewpoint is that cognitive reserve affects the clinical expression but has no direct effect on AD pathology. This viewpoint was re-examined in our study. The results showed that higher cognitive reserve indexed by education and other proxies was associated with slower rates of AD pathological deterioration, particularly among cognitively normal elderly people. These findings suggest that the pathological course of AD can be modified by cognitive reserve.