Inflammaging and Cognitive Decline: A Brief Review of the Chronic Low-Grade Neural Inflammation Hypothesis

This presentation reviews the chronic low‑grade neural inflammation hypothesis as a mechanism linking aging to cognitive decline. Inflammaging(definition) refers to persistent, low‑level inflammation that develops with age due to immune dysregulation in the absence of infection. In the brain, this process is often triggered by the accumulation of beta‑amyloid plaques and phosphorylated tau tangles. Microglia attempt to clear these proteins, but their prolonged activation releases inflammatory mediators that damage surrounding neurons. Over time, this sustained neural inflammation contributes to neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, epilepsy, and psychiatric disorders including schizophrenia and major depression. Imaging markers like TSPO highlight elevated inflammation in vulnerable regions, such as the hippocampus in amnestic Alzheimer’s disease. As the U.S. population ages and the proportion of older adults grows, understanding inflammaging has increasing public‑health significance. Clarifying how chronic neural inflammation develops—and how it might be slowed or prevented—could reduce the burden of age‑related cognitive disorders on families, caregivers, and healthcare systems.