Modeling functional loss in Alzheimer’s Disease through cognitive reserve and cognitive state: a panel data longitudinal study

Cognitive Reserve (CR) refers to the brain's ability, supported by active and modifiable forms of lifestyle compensation, to cope with neural changes due to age or disease, delaying the onset of cognitive deficits. In CR studies, neuropsychological performances and functional autonomy are considered alternative outcomes. While decreased functional independence gains importance in dementia diagnosis and monitoring, cognitive functioning may play a role in staging its severity. The main aim of the present study was to test a longitudinal model of Alzheimer’s Disease (AD), in which CR (years of education) and current cognitive status (Mini-Mental State Examination, MMSE, score) would predict clinical progression in terms of loss of functional independence at a later time. From the ADNI database, we considered 308 AD participants, and for 180 of them, we could extract CSF Aβ1-42 baseline levels as an index of amyloid burden. Functional decline (one-year delta score at the Functional Activities of Daily Living Questionnaire) was explained by the CR and MMSE score interaction net of age; a trend was found also when controlling for amyloid burden. Functional decline at one year was increased for patients with high CR levels and low MMSE and with low CR and high cognitive state, compared to the opposite. The present investigation demonstrated the mutual role of past acquired CR and current cognitive status in predicting functional progression in AD. The study suggests a way to predictively interpret available demographic and clinical data, defining differential longitudinal trajectories that might be useful for clinical management.