The aging process correlates with a progressive failure in the normal cellular and organ functioning; these alterations are aggravated in Alzheimer’s disease (AD). In both aging and AD there is a general decrease in the capacity of the body to eliminate toxic compounds and, simultaneously, to supply the brain with relevant growth and nutritional factors. The barriers of the brain are targets of this age related dysfunction; both the endothelial cells of the blood–brain barrier and the choroid plexus epithelial cells of the blood-cerebrospinal fluid barrier decrease their secretory capacity towards the brain and their ability to remove toxic compounds from the brain. Additionally, during normal aging and in AD, the permeability of the brain barriers increase. As such, a greater contact of the brain parenchyma with the blood content alters the highly controlled neural environment, which impacts on neural function. Of interest, the brain barriers are more than mere obstacles to the passage of molecules and cells, and therefore active players in brain homeostasis, which is still to be further recognized and investigated in the context of health and disease. Herein, we provide a review on how the brain barriers change during aging and in AD and how these processes impact on brain function.

Appropriate decision-making relies on the ability to shift between different behavioral strategies according to the context in which decisions are made. A cohort of subjects exposed to prolonged stress, and respective gender- and age-matched controls, performed an instrumental behavioral task to assess their decision-making strategies. The stressed cohort was reevaluated after a 6-week stress-free period. The behavioral analysis was complemented by a functional magnetic resonance imaging (fMRI) study to detect the patterns of activation in corticostriatal networks ruling goal-directed and habitual actions. Using structural MRI, the volumes of the main cortical and subcortical regions implicated in instrumental behavior were determined. Here we show that chronic stress biases decision-making strategies in humans toward habits, as choices of stressed subjects become insensitive to changes in outcome value. Using functional imaging techniques, we demonstrate that prolonged exposure to stress in humans causes an imbalanced activation of the networks that govern decision processes, shifting activation from the associative to the sensorimotor circuits. These functional changes are paralleled by atrophy of the medial prefrontal cortex and the caudate, and by an increase in the volume of the putamina. Importantly, a longitudinal assessment of the stressed individuals showed that both the structural and functional changes triggered by stress are reversible and that decisions become again goal-directed.