Linking cortical structure and delirium in the elderly: insights from cohort study and shared genetic risk analysis

This study aimed to assess the association between regional cortical changes measured via baseline magnetic resonance imaging (MRI) and the incidence of delirium.

Observational associations were assessed using a prospective cohort from the UK Biobank and an independent clinical cohort. The population-based study included participants aged 60 years or older who had undergone structural brain MRI since 2014. Regional cortical volume, mean thickness, and surface area were extracted based on the Desikan-Killiany cortical atlas. Delirium was defined using ICD-10 diagnostic codes. Additionally, preoperative brain MRI images from participants in another cohort were collected and automatically segmented using deep learning algorithms to obtain cortical measurements. Logistic analysis was performed to investigate the associations between cerebral cortical structure and delirium risk. Lastly, genome-wide association study data derived from the ENIGMA Consortium and FinnGen Biobank were utilized to conduct conditional/conjunctional false discovery rate (cond/conjFDR) analyses to identify shared genetic loci associated with cortical structures and delirium.

This observational analysis included 31,890 participants from the UK Biobank and 152 participants from an independent cohort. In the UK Biobank cohort, decreased cortical thickness in the 17 regions was associated with a significantly increased risk of delirium. Similarly, a preoperative reduction in cortical volume in 7 regions was associated with an increased risk of delirium in the independent cohort. Besides, 100 single-nucleotide polymorphisms (SNPs) were identified as significantly associated with cortical structures when conditioned on delirium. Finally, colocalization analysis demonstrated that these pleiotropic risk loci modulated the expression of NT5C2, RGP1, CCDC25, TPM2, EEF1AKMT2, IQANK1 and LHPP in blood and brain tissues.

Regional cortical atrophy is associated with an increased risk of delirium in the elderly. Brain MRI examinations may be beneficial for preoperative delirium risk assessment in elderly individuals undergoing elective surgery.