Thinking outside the brain for cognitive improvement: Is peripheral immunomodulation on the way?

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Cognitive impairment is prevalent in aging and neurodegenerative diseases like Alzheimer's Disease (AD).
• Current research primarily focuses on the central nervous system (CNS) for cognitive decline interventions.
• Emerging evidence highlights the critical role of systemic factors and brain-periphery communication in cognitive function.

Purpose of the Study:

• To explore a non-neurocentric understanding of cognitive impairment pathogenesis.
• To discuss novel therapeutic strategies targeting brain-periphery interactions.
• To examine the diagnostic and therapeutic implications of systems-based approaches.

Main Methods:

• Review of recent advances in understanding cognitive deficits from a systems perspective.
• Analysis of the bidirectional crosstalk between the CNS and the peripheral immune system.
• Discussion of neuroimmune, neuroendocrinal, and bioenergetic mechanisms involved.

Main Results:

• Recent advances provide a systems-level perspective on cognitive deficits.
• Brain-periphery interactions are crucial for neuronal survival and function.
• Therapeutic interventions targeting these interactions may not require CNS entry.

Conclusions:

• A systems-based, non-neurocentric view is essential for understanding cognitive impairment.
• Targeting brain-periphery interactions offers promising therapeutic avenues for cognitive disorders.
• Clinical translation of these findings requires careful consideration of key issues.