Cognitive reserve analysis using functional MRI

The new consensus definition of cognitive reserve (CR) provides a framework to study individual differences in cognitive functioning relative to aging and disease. CR denotes a property of the brain that allows for better than expected cognitive performance given the degree of age-related brain changes or disease. More specifically, individual differences in patterns of brain activity during fMRI tasks might explain the differential susceptibility to pathological burden. According to the consensus definitions, we sought to identify and quantify CR from an fMRI task of subsequent memory in a large multi-centric sample (DELCODE) consisting of 202 participants with subjective cognitive decline, 64 with mild cognitive impairment, 21 with Alzheimer’s disease (AD) dementia, 51 AD relatives and 152 cognitively normal controls. Individual measures of CSF amyloid-ß42:40 ratio, CSF p-tau and hippocampal volume were reduced to a single number, representing an AD pathological load score. Subsequently, a multivariate moderation model is developed to identify a CR-related activation pattern of successful memory encoding that moderates this relationship.