Traumatic Brain Injury and Dementia: Mechanisms, Risk Stratification, and Clinical Management.

Traumatic brain injury (TBI) is one of the main mechanisms underlying health issues associated with functional and structural brain changes. While direct effects such as cognitive and physical impairments are well documented, recent research has linked TBI to neurodegenerative changes similar to dementia. TBI-related neurodegeneration includes progressive brain-tissue degeneration that leads to behavioral changes, cognitive decline, and dementia-like symptoms. The exact underlying mechanisms are complex, and include neuroinflammation, oxidative stress, excitotoxicity, and disruption to protein homeostasis. Neuroinflammation is controlled by the activation of astrocytes and microglia and causes neuronal damage and the prolonged release of proinflammatory cytokines. Oxidative stress damages cell and impairs mitochondrial function, while the accumulation of misfolded proteins such as tau and β-amyloid mimics the pathology of Alzheimer's disease. Excitotoxicity involves excessive neurotransmitter release that may lead to further injuries. Epidemiological studies show that the risk of dementia is increased after moderate-to-severe TBI and influenced by age and genetic factors. Current management strategies focus on symptom relief, and there is ongoing research aimed at improving the understanding of the underlying mechanisms and the development of effective treatments.