Abstract:

Background: Delirium is common and age, frailty and dementia are risk-factors. The pathophysiology is complex and poorly understood, but age-related immune system changes may be key. This study aimed to measure markers of immune cell migration, accelerated immune ageing and blood-brain barrier permeability in community-dwelling, older people comparing those who developed ≥1 episode of delirium over 2 years with those that did not.

Methods: Baseline samples were collected from CASCADE participants who were followed up for 2 years. Delirium screening was performed weekly; positive screens or hospital admission triggered a delirium assessment. Serum was isolated, stored and analysed using a multiplex panel comparing levels between participants with and without delirium episodes.

Results: About 98 participants were included. Median age was 88 (IQR: 81.8-92.0), with 90.8% classified as frail. Forty-three participants (43.9%) experienced ≥1 delirium episodes. CCL2 (MCP-1) and CXCL2 (MIP-2α), measured in a stable state at baseline, were significantly higher in the delirium group compared to the no delirium group (13.38 (11.21-17.93) vs. 10.83 (9.03-14.64) P = .004) and (17.23 (11.80-24.22) vs. 13.49 (10.19-17.98) P = .031), respectively. When stratified by dementia status, the associations of CCL2 with delirium were maintained in both groups, but CXCL2 was only significantly higher in delirium in the subgroup without dementia.

Discussion: CCL2 and CXCL2 are chemokines involved in immune cell recruitment and markers of accelerated immune ageing. Future work should elucidate the role of immune cell recruitment and brain infiltration in delirium, to identify treatment targets. Furthermore, work should explore whether targeting immune ageing can reduce delirium risk.

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