Biomarkers of delirium and relation to dementia among the elderly in the intensive care unit: A narrative review

Abstract

Delirium is a neuropsychiatric disorder highly prevalent in the intensive care unit (ICU), especially among elderly patients. Symptoms develop suddenly over a short period of time in the form of a fluctuating mental state marked by severe inattention and disturbance in cognition. Dementia, on the other hand, develops over a long period of time as a result of a neurodegenerative disorder. In this review, we aim to identify overlapping biomarkers between delirium and dementia to have a better understanding of the underlying pathophysiological mechanisms relating these two disorders. Overlapping biomarkers included low levels of albumin and IGF-1, a presence of the APOE ε4 allele (APOE ε4 +), as well as higher levels of of AβN-40, S100β, procalcitonin, IL-1β, NfL, prolactin, creatinine, MMP-9, and homocysteine. We put forward several hypotheses on the convergence of the pathophysiology of these two disorders. It is plausible that ICU-acquired delirium arises as a sign of prodromal dementia or as a result of chronic systemic inflammation and concomitant neuroinflammation due to an increase in S100β proteins in the brain as a byproduct of chronic glial activation. Simultaneously, accumulation of creatinine may render the functioning of the kidneys sub-optimal, which can have deleterious effects on cognitive functioning, while lower serum albumin can increase the risk of Aβ accumulation in the brain and therefore increase the likelihood of delirium and future dementia. Moreover, homozygosity in the APOE ε4 allele coupled with elevated plasma CRP might increase the risk of delirium and trigger the onset of Alzheimer’s disease (AD). Therapeutic approaches targeting the above biomarkers need to be the subject of further investigation, especially among those exhibiting persistent delirium.