Delirium and Associations with Atrophy Rate on Serial Volumetric MRI: A Prospective UK Cohort Study

Abstract

Background: Delirium is associated with long-term cognitive impairment, but the underlying pathophysiology is unclear. In individuals reporting historic delirium symptoms, we examined MRI-derived rates of atrophy and the influence of baseline brain health. We hypothesised delirium would be associated with increased atrophy, independent of amyloid-beta (Abeta), white matter hyperintensity volumes (WMHV) and plasma neurofilament light (NfL) concentration. Methods: Volumetric MRI and 18F-florbetapir Abeta-PET scans were conducted at two time-points in individuals in Insight 46, the neuroscience sub-study of the 1946 British Birth Cohort. Participants with two high quality scans and no major brain disorder (including dementia) at follow-up were included. Linear regression was used to examine associations between self or informant-reported delirium after age 50, and rates of whole-brain, hippocampal and ventricular volume change (quantified using the boundary shift integral) between ages 71 and 73 (mean scan interval 2.4 years). Analyses were adjusted for multiple a priori biological and social factors, including total intracranial volume, Abeta positivity, WMHV and plasma NfL concentration. Findings: Of 323 participants (48% female, mean age at first scan 70.2), 53 (16%) reported a history of delirium. Delirium was associated with a 15% increased rate of whole-brain atrophy (-0.98ml/yr change, 95% CI -1.84ml to -0.11ml, p=0.028) but not with disproportionate hippocampal or ventricular atrophy. Loss was predominantly in grey matter. Associations were independent of, and had a similar magnitude of effect to that of Abeta positivity, a 10ml increase in WMHV, or doubling of plasma NfL at baseline. Interpretation: Historic delirium is associated with faster atrophy, independent of key markers of baseline brain health in cognitively intact older adults. These findings are consistent with delirium being independently associated with neurodegeneration, likely unrelated to Alzheimer's disease.Copyright © 2025, The Authors. All rights reserved.