Persistent Chronic Inflammation Raises the Risk of Neurodegenerative Disease

In this open access paper, the authors present evidence for chronic inflammation to contribute to the development of neurodegenerative disease. A great deal of research into the late stage disease state robustly connects inflammation to pathology, and given the risk factors for neurodegeneration, such as excess visceral fat tissue, it is entirely reasonable to think that inflammation is important. It accelerates the development of many other age-related conditions, after all. Less work has been carried out on the early stages of development of neurodegenerative diseases in humans, however, due to the lack of good data sets that span the necessary decades of time. There are already many good reasons to minimize chronic inflammation throughout life, to as great a degree as is possible. This one can be added to the stack.

Although it has become clear over the last several decades that inflammation plays a role in the pathogenesis of Alzheimer's disease and other forms of dementia, the precise nature and temporal characteristics of the neurodegeneration-inflammation relationship have remained largely unknown. Several lines of research have identified inflammation, both within the brain and within the periphery, as a potential driver of neurodegenerative brain changes and cognitive decline. Chronic low-grade inflammation, in particular, has received considerable attention, as translational studies suggest that it may play a causal role in dementia, late-life cognitive decline, and a number of other age-related phenotypes.

Although evidence from animal models indicates that chronic inflammation can perpetuate, or even initiate, neurodegenerative changes, this hypothesis has been challenging to examine in human studies. This is largely due to a lack of longitudinal data on inflammatory biomarkers in cohort studies which examine neurocognitive outcomes in older adults. In a recently published study of participants from the Atherosclerosis Risk in Communities (ARIC) Cohort, we were able to clarify the relationship between long-term (21-year) patterns of systemic inflammation and late-life neurodegenerative changes.

In this study, we found that individuals who both demonstrated elevated inflammation before or during middle adulthood and maintained high levels of inflammation over the subsequent two decades had greater white matter hyperintensity volume and reduced white matter microstructural integrity as older adults, compared to those who maintained low levels of inflammation. These findings support the idea that systemic inflammation can initiate or perpetuate neurodegenerative brain changes which underlie cognitive impairment and dementia.

Link: https://doi.org/10.18632/aging.101704

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