Mechanisms of Cognitive Aging: The Roles of Brain Iron Accumulation and Neuroinflammation

Age-related cognitive impairments compromise the functional capacity of aging individuals, and create major individual and societal costs. Therefore, understanding the mechanisms underlying cognitive aging is of great importance. Increasing evidence suggests that metabolically active iron particles increase in the aging brain, disrupting optimal neural functioning. At the same time, human aging is characterized by chronic, low-grade inflammation, with negative consequences on cognition. Based on initial evidence, we hypothesize that an overload of iron is deleterious, as it may induce chronic inflammation. We also address the alternative hypothesis that high systemic inflammation precedes and predicts iron accumulation across three years. Moreover, neuroinflammation may be independent of iron, but still contribute to cognitive performance. The latter scenario may be particularly true for brain regions with low iron accumulation.

The overarching goal of this research project is to determine the role of iron accumulation in the aging brain as a mechanism underlying neuroinflammation and concomitant impairments in cognitive as well as motor functions. Without a mechanistic understanding, intervention efforts to delay cognitive decline are likely to fail, because they may not focus on the causal factors. Overall, our findings will contribute to a better understanding of individual cognitive and brain aging trajectories.

This project is funded by the Swedish Research Council (VR).