What Does the Brain Have to Keep Working at Its Best? Resilience Mechanisms Such as Antioxidants and Brain/Cognitive Reserve for Counteracting Alzheimer’s Disease Degeneration

SIMPLE SUMMARY: Alzheimer’s disease currently represents one of the major challenges of modern society in relation to social and medical costs. As people age, they often experience mild changes in cognitive functioning that may be due to an initial degeneration of cerebral networks. Advances in neurobiology research including antioxidants intake and brain capacity to resist damage is relevant in order to support elderly people in the adoption of healthy lifestyles able to counteract dementia onset. ABSTRACT: Here we performed a narrative review highlighting the effect of brain/cognitive reserve and natural/synthetic antioxidants in exerting a neuroprotective effect against cognitive deterioration during physiological and pathological aging. Particularly, we discussed pathogenesis of Alzheimer’s disease, brain and cognitive reserve as means of resilience towards deterioration, and evidence from the literature about antioxidants’ role in sustaining cognitive functioning in the preclinical phase of dementia. During aging, the effects of disease-related brain changes upon cognition are reduced in individuals with higher cognitive reserve, which might lose its potential with emerging cognitive symptoms in the transitional phase over the continuum normal aging-dementia (i.e., Mild Cognitive Impairment). Starting from this assumption, MCI should represent a potential target of intervention in which antioxidants effects may contribute—in part—to counteract a more severe brain deterioration (alongside to cognitive stimulation) causing a rightward shift in the trajectory of cognitive decline, leading patients to cross the threshold for clinical dementia later.