Neuropathological approaches to cerebral aging and neuroplasticity

Cerebral aging is a complex and heterogenous process related to a large variety of molecular changes involving multiple neuronal networks, due to alterations of neurons (synapses, axons, dendrites, etc), particularly affecting strategically important regions, such as hippocampus and prefrontal areas. A substantial proportion of nondemented, cognitively unimpaired elderly subjects show at least mild to moderate, and rarely even severe, Alzheimer-related lesions, probably representing asymptomatic preclinical Alzheimer's disease, and/or mixed pathologies. While the substrate of resilience to cognitive decline in the presence of abundant pathologies has been unclear, recent research has strengthened the concept of cognitive or brain reserve, based on neuroplasticity or the ability of the brain to manage or counteract age-related changes or pathologies by reorganizing its structure, connections, and functions via complex molecular pathways and mechanisms that are becoming increasingly better understood. Part of neuroplasticity is adult neurogenesis in specific areas of the brain, in particular the hippocampal formation important for memory function, the decline of which is common even in “healthy” aging. To obtain further insights into the mechanisms of brain plasticity and adult neurogenesis, as the basis for prevention and potential therapeutic options, is a major challenge of modern neurosciences.