It's been suggested that inflammation is closely connected to cognitive decline, and neuroinflammation is known to play a role in the development of Alzheimer's disease (AD). It seems that secondary infections, even when they do not occur in the brain, can cause AD patients to decline cognitively even faster. In AD, certain brain cells called astrocytes and microglia are thought to be overactivated. Microglia are critical to immune function in the brain. Astrocytes have a variety of functions, including helping maintain homeostasis.
Researchers have suggested that when new events happen that trigger an inflammatory response, there is also an immune response in the brain that affects memory in both mice and humans. Reporting in Alzheimer's & Dementia, scientists have used a mouse model of AD to examine the effects of acute inflammatory events on the function of neural networks, inflammation in the brain, and memory. The work suggested that secondary infections cause astrocytes and microglia to become even more overactive, which further disrupts cognition and rhythms in the brain.
The mouse model used in this work had more cognitive impairment and disorder in brain rhythms compared to age-matched mice that were healthy. The researchers suggested that the changes seen in these mice mimic those seen in elderly AD patients. The astrocytes and microglia in the mouse model were altered as well.
In people with AD who had died, those that had a systemic infection also had higher levels of a pro-inflammatory molecule called IL-1β. That is the same molecule that is thought to cause the changes seen in the mouse model, like the heightened immune response.
"Alzheimer's disease is the most common form of dementia, affecting more than five percent of those over 60 and this distressing, debilitating condition causes difficulties for a huge number of people across the globe. The more we know about the disease and its progression the better chance we have of treating those living with it. We believe our work adds to this knowledge base in a few ways. Primarily, we show that the Alzheimer's-affected brain has a greater vulnerability to acute inflammatory events, even if they occur outside the brain," said study leader Colm Cunningham, Associate Professor in Trinity's School of Biochemistry and Immunology, and the Trinity Biomedical Sciences Institute.
"Placing this within the context of the slowly evolving progression of AD, we propose that these hypersensitive responses, now seen in multiple cell populations, may contribute to the negative outcomes that follow acute illness in older patients, including episodes of delirium and the accelerated cognitive trajectory that has been observed in patients who experience delirium before or during their dementia."