Dual impact of neuroinflammation on cognitive and motor impairments in Alzheimer's disease

Abstract

Neuroinflammation plays a crucial role in the progression of Alzheimer's disease (AD), contributing to both cognitive decline and motor impairment. This review examines the dual impact of neuroinflammatory processes, particularly the activation of microglia and astrocytes, and the dysregulated release of pro-inflammatory cytokines and chemokines, on cognition and balance in AD. Neuroinflammation leads to synaptic dysfunction, oxidative stress, and mitochondrial impairment, which accelerate neuronal damage and disrupt motor circuits, such as those in the motor cortex, basal ganglia, and cerebellum. These disruptions result in motor symptoms like gait disruption and balance issues, reflecting the close interplay between cognitive and motor functions. In addition, we highlighted the role of blood-brain barrier disruption and peripheral neuropathy in increasing motor dysfunction. Despite the promise of anti-inflammatory treatments, clinical trials with non-steroidal anti-inflammatory drugs have yielded mixed results, underscoring the need for early intervention and more targeted therapies. Therefore, understanding the mechanisms linking neuroinflammation to cognitive and motor impairments may guide the development of new therapeutic approaches aimed at mitigating the complex pathology of AD.