• Middle-aged mice given repeated bacterial exposures (infections) have decreased memory retention during maze tests.
  • Repeated infections lead to inflammation in the hippocampus, part of the brain which is primarily responsible for learning and memory formation.
  • Inflammation in the hippocampus leads to decreased communication between nerve cells (neurons) and reduced memory retention.

Age-related cognitive decline is a common part of the aging process affecting over 20% of older adults in the U.S. Cognitive decline is often accompanied by significant impairment in daily functioning and decreased quality of life. A recent study shows that repeated infections during adulthood may negatively affect cognitive, suggesting that preventing such infections may help stave off age-related cognitive concerns.

The study, a collaboration amongst a few U.S.-based institutions and published in Brain, Behavior, and Immunity, focuses on middle-aged mice exposed every couple of weeks to increasing doses of LPS (lipopolysaccharide) – a bacterial component used to elicit immune responses and inflammation. The scientists found that the aged mice had impaired learning and memory following repeated LPS exposure. The mice also had increased inflammation and disrupted long-term potentiation – the process by which connections between neurons get stronger with repeated activation, a basis for memory and learning – in the hippocampus. The researchers suggest that this data has significant implications for older adults who may suffer from repeated infections.

“The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia,” the scientists wrote.

Repeated Infection Affects Memory and Retention

The scientists injected 10 month old mice (around 40 in human years) with five injections of LPS over the course of 10 weeks. The mice were assessed for health on a 20-point scale, ensuring that they recovered from their illness within the two weeks following each injection. 

Following the 10 weeks of treatment, Engler-Chiurazzi and colleagues ran tests to assess the cognitive abilities of the mice. The open field test – which looks at activity levels, mobility, and exploration habits – and tests to assess pain sensation were unaffected by the repeated LPS exposures. However, tests that measured memory retention, such as a shock avoidance test and a hidden platform water maze, were affected by LPS treatment, suggesting that repeated infections affect memory retention and sustained learning.

(Engler-Chiurazzi et al., 2023 | Brain, Behavior, and Immunity) Repeated LPS Exposures Affect Memory Retention Mice given LPS injections (gray) had B) decreased immediate retention and 24-hour retention as compared to placebo-treated mice (white) during a shock avoidance test, as well as Eii) decreased retention when attempting to find an underwater platform on the first trial of the day (Trial 1) as compared to the last trial of the previous day (Trial 6), indicating less overnight memory as compared to placebo-treated mice (white).

Hippocampal Inflammation and Decreased Neuronal Connection with Repeated Infections

To assess how the LPS may be affecting learning and memory, the investigators looked at inflammation in the hippocampus, which as mentioned previously plays a major role in learning and memory. They found that repeated LPS exposure increases IL-6 levels in the hippocampus. IL-6 is a pro-inflammatory cellular messaging molecule shown to be important for tissue damage-induced immune response, which may occur with repeated infections.

(Engler-Chiurazzi et al., 2023 | Brain, Behavior, and Immunity) Repeated LPS Exposures Increases Inflammation in the Hippocampus Mice treated with LPS had increased IL-6 in their hippocampus, but not in the cortex – another part of the brain which is not as associated with memory creation – as compared to placebo treated mice (Veh)

Having seen inflammatory effects in the hippocampus, the researchers looked at the effects of repeated LPS on LTP (long-term potentiation), a very prominent process in the hippocampus given its role in forming long term memory. They found that mice given repeated LPS injections had less LTP, indicative of less long-term synaptic plasticity – the ability to change and form new connections (synapses) between neurons – than those given placebo injections. 

Inflammation and Cognitive Decline

Engler-Chiurazzi and colleagues show here how repeated infections may play a role in cognitive decline, particularly when it comes to learning and memory retention, further suggesting that anti-inflammatory therapies may show promise in preventing cognitive dysfunction as we age. This study also highlights the ways in which we must be wary of infectious diseases running rampant through retirement communities and assisted living facilities, with the investigators going so far as to suggest that more aggressive infection interventions are warranted among those at high risk for dementia.

Other studies have previously linked cognitive concerns and inflammation, including showing that an anti-inflammatory Psoriasis medication can protect against Alzheimer’s disease and linking severe covid to accelerated brain aging, but this is the among the first linking smaller, repeated infections and their cumulative effects to cognitive decline. More research is needed into the association between infections and cognitive decline, but it seems as though staying our healthiest can only benefit us as we age.