Immune Drain

How acute and chronic infections can reinforce metabolic stress in the brain

An abundance of chronic bacterial invaders can damage the bladder and kidneys) , gut lining), and gums). This damage triggers chemical alarm messengers (inflammatory cytokines) that can reach the bloodstream. These chemical alarm messengers can alert the brain via visceral afferent pathways (the brain’s sensory antennas for the body) or the blood brain barrier (Wang et al., 2022¹; Tracey, 2002² ) When brain cells detect these alarm signals, they can respond by downshifting their energy production and releasing amyloid: a response that can cause a sudden onset of agitation or withdrawal (Holmes et al., 2003³; Cunningham et al., 2021⁴; Giridharan et al., 2019⁵; Soscia et al., 2010⁶ ). This metabolic downshift response and release of antimicrobial amyloid peptides is normally a temporary defense strategy: neutralize incoming threats by cutting off energy supply to a potential influx of invaders (Nathan & Ding, 2010⁷) After the threat has passed, brain cells resume normal metabolic operations and restore healthy metabolism.

However, under conditions of pre-existing metabolic stress (energy deficit), the hallmark of Alzheimer’s disease (Cunnane et al., 2020⁸; ), the brain cells have difficulty resuming normal operations and cleaning up the amyloid peptides: doing so requires resources that a metabolically stressed brain cannot adequately provide) (Lauro & Limatola, 2020⁹; Yin et al., 2016¹⁰). As recurrent UTIs continue, amyloid deposits remain without cleanup, and further vascular damage leaves the system even more vulnerable than before (Asby et al., 2021¹¹)

In this condition of systemic metabolic stress and dementia, a vicious cycle can become entrenched: a body and brain stuck in a loop of bacterial invaders, responding to the invasion by downshifting metabolism, lacking the resources to resume normal cleanup and metabolic operations, followed by another wave of invaders attacking an already stressed system. Both acute infections (UTIs) and chronic bacterial loads (constipation, periodontitis) can contribute to this vicious cycle (Fong et al., 2009¹²).

How to reduce the immune drain

People living with dementia are more vulnerable to acute and chronic infections (Kim et al., 2026¹³). They also have impaired metabolism, making it more difficult to overcome infections, potentially leading to a runaway state of self-reinforcing dysregulation (Karin & Alon, 2017¹⁴) Reducing persistent stressors, alongside supporting metabolism, may help to improve the potential for restoring an improved level of systemic regulation.

In practical terms, maintaining an effective oral health routine, preventing constipation, and preventing UTIs are actionable steps that individuals and their caregivers can take to give their bodies a better chance at maintaining the best regulation possible. In the case of dementia, increased difficulty with communication, mobility, initiating actions, and changes in sensitivity make managing stress on the immune system more difficult, and caregivers, healthcare providers, and institutions must provide increased vigilance in these areas. Despite the difficulty, investments in these basic body health measures can reap outsized benefits in terms of preventing further decline.