Imaging markers of neuroinflammation in aging and Alzheimer's disease and related dementia: A comprehensive review

Abstract

Neuroinflammation represents a key pathophysiological process contributing to cognitive decline during aging and may play a significant role in the development of Alzheimer’s disease and related dementia (ADRD). Many magnetic resonance imaging (MRI) studies have investigated the extent and impact of neuroinflammation in older adults and in individuals at various stages of ADRD. These imaging techniques enable the assessment of blood-brain barrier (BBB) permeability, structural damage in white and gray matter, and functional brain impairment. In this review, we summarize the advantages and limitations of various MRI protocols used to study neuroinflammation. With a focus on neuroinflammation, studies that characterized structural and functional brain changes but did not relate the findings to neuroinflammation were outside the scope of this review. However, we provided a brief survey on studies combining multiple imaging modalities for readers to have a broader view on neuroinflammation, aging, and ADRD. We first begin by introducing MRI techniques used to examine BBB dysfunction, neuroinflammation, gray and white matter deficits, and functional brain changes. Next, we reviewed studies investigating neuroinflammation in aging, followed by examination of imaging studies of ADRD in this context. Collectively, these findings indicate that both aging and AD are associated with progressive BBB dysfunction contributing to cognitive decline. Additionally, neural markers derived of diffusion tensor imaging, magnetic transfer imaging, MR spectroscopy, structural imaging, and functional connectivity provide valuable insights into neuroinflammatory processes. This body of research highlights MRI’s potential as a non-invasive tool for monitoring neuroinflammation and tracking disease onset and progression.