Do infections accelerate cognitive decline?

The risk for infection-related complications increases with age due to changes in immune system responses. One of these complications is the acceleration of cognitive decline. Infections can cause short term cognitive impairments which are reversible once the infection is cleared, but they can also lead to long-term cognitive impairments in people who are already on the trajectory toward dementia. In effect, an infection can unmask dementia in people with subtle symptoms.

Longitudinal studies have found that hospitalization for common infections, such as pneumonia and urinary tract infections, is associated with at least 1.4-fold higher risk for dementia in otherwise well-functioning older adults [1; 2]. The risk was similar for those with mild cases not requiring intensive care compared with those with severe life-threatening cases, suggesting the risk does not depend on the severity of infection. But there is evidence it may depend on the frequency of infection, such that having repeated bouts of infection further increases dementia risk in the elderly [3]. This increased risk is driven by dysfunctional immune system responses in people predisposed to dementia.

There is evidence for a bidirectional relationship between immune system dysfunction and dementia, highlighting the role of the immune system in dementia onset and progression [2]. People with dementia have an increased risk for infection, which may be due to an altered immune response, while a poor immune response to infection places elderly individuals at increased risk for dementia.

In healthy young adults, the immune system mounts a strong early response to a virus or microbe, which leads to a fast recovery. As the immune system ages, it can become dysfunctional, leading it to mount a weak early response that is ineffective in clearing the microbe. This then induces the body to mount a very strong late response, leading to systemic inflammation. It is this inflammatory response which drives cognitive impairment. Communication between immune cells and neural cells is important for the maintenance of cognitive function. Inflammation can disrupt this communication, leading to cognitive impairment [4].

Inflammation in the brain can lead to delirium, or acute mental confusion [5]. People with dementia as well as those with subclinical symptoms who are on the trajectory toward dementia are at highest risk for delirium. Indeed, acute delirium can be one of the presenting signs of infection in someone with dementia. A recent study found that the immune system changes that take place during infection-related delirium are the same as those that cause neuronal damage in Alzheimer’s disease [6]. Therefore, these bouts of infection-related brain inflammation amplify processes underlying cognitive decline, which may explain why infections accelerate cognitive decline in people with or without overt pre-existing symptoms.

The best way to protect oneself from infection-related cognitive decline is to prevent infections in the first place by engaging in activities that boost the immune system, such as getting exercise and eating a healthy diet, as well as getting immunizations and practicing good hygiene. Urinary tract infections can be prevented with good perineal hygiene, while periodontitis can be prevented and treated with good oral hygiene. Immunizations are the most effective method to prevent severe infections for pneumonia, flu, and shingles.

1. Tate JA, Snitz BE, Alvarez KA et al. (2014) Infection hospitalization increases risk of dementia in the elderly. Crit Care Med 42, 1037-1046.
2. Shah FA, Pike F, Alvarez K et al. (2013) Bidirectional relationship between cognitive function and pneumonia. Am J Respir Crit Care Med 188, 586-592.
3. Dunn N, Mullee M, Perry VH et al. (2005) Association between Dementia and Infectious Disease: Evidence from a Case-Control Study. Alzheimer Disease & Associated Disorders 19, 91-94.
4. Perry VH, Cunningham C, Holmes C (2007) Systemic infections and inflammation affect chronic neurodegeneration. Nature Reviews Immunology 7, 161-167.
5. Atterton B, Paulino MC, Povoa P et al. (2020) Sepsis Associated Delirium. Medicina (Kaunas) 56, 240.
6. Peters van Ton AM, Verbeek MM, Alkema W et al. (2020) Downregulation of synapse-associated protein expression and loss of homeostatic microglial control in cerebrospinal fluid of infectious patients with delirium and patients with Alzheimer’s disease. Brain, Behavior, and Immunity.

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