Memory impairments in healthy aging: Role of aging-induced microglial sensitization

Healthy aged individuals are more likely to suffer profound memory impairments following a challenging life event such as a severe bacterial infection, surgery, or an intense psychological stressor, than are younger adults. These peripheral challenges are capable of producing a neuroinflammatory response, (e.g., increased pro-inflammatory cytokines), and in the healthy aged brain this response is exaggerated and prolonged. Normal aging primes or sensitizes microglia and this appears to be the source of this amplified response. Among the outcomes of this exaggerated neuroinflammatory response is an impairment in synaptic plasticity, and a reduction in key downstream mediators such as Arc and BDNF. Each of these mechanisms is important for long-term memory formation, and is compromised by elevated pro-inflammatory cytokines. Pharmacological, dietary and physical interventions are discussed as potential therapies to abrogate the challenge-induced neuroinflammatory response, thereby preventing or reducing memory deficits in aged subjects.