Stata code for analyses of associations between delirium and longitudinal volumetric MRI imaging. Sample from Insight 46 cohort, used for the paper "Delirium and associations with atrophy rate in serial volumetric MRI: A prospective UK cohort study". Full link to be provided when published.
Background & Objectives:
Delirium is associated with longitudinal decline in cognition, but possible underlying pathophysiology is poorly understood. We used neuroimaging to examine longitudinal changes in brain structure, adjusting for the presence of amyloid (Aβ) plaque deposition and white matter hyperintensity volumes (WMHV), for individuals with reported delirium in the last twenty years. We hypothesised delirium would be associated with an increased rate of whole-brain atrophy, independent of atrophy caused by Aβ deposition and WMHV.
Methods:
Serial volumetric MRI and Aβ PET scans were conducted on individuals enrolled in the Insight 46 neuroimaging study (a sub-study of the British 1946 Birth Cohort), who had no major brain disorder (including dementia) at follow-up. Participants with two high quality scans were included. Linear regression was used to examine associations between self or carer-reported delirium between the ages of 50 and 70, and rate of whole-brain atrophy between ages 71 and 73 (mean scan interval 2.4 years). Analyses were adjusted for sex, age at first scan, chronic disease count, polypharmacy, APOE genotype, and baseline brain volume, Aβ deposits and WMHV.
Results:
Among 326 participants (156 female, mean age at first scan 70.2), 54 reported delirium. Delirium was associated with an increased rate of whole-brain atrophy (1.06ml increased volume loss per year, 95% C.I. 0.20ml to 1.92ml, p=0.02) but not with disproportionate hippocampal atrophy or ventricular expansion. Associations were independent of Aβ positivity and WMHV at baseline, which both displayed associations with increased rates of whole-brain atrophy (Aβ positivity: 1.00ml increased volume loss per year, 95% C.I. 0.14ml to 1.86ml, p=0.02 & WMHV: 0.09ml increased volume loss per year per additional ml of WMHV, 95% C.I. 0.03ml to 0.14ml, p<0.01).
Discussion:
Delirium is associated with a higher risk of later life dementia, and increased rates of whole-brain atrophy, independent of cerebral Aβ deposition and WMHV, may highlight pre-clinical changes in brain structure related to prodromal dementia. However, participants were excluded from our study if they had developed dementia at follow up, and had no demonstrable differences in Pre-clinical Alzheimer’s Cognitive Composite scores. Our findings may suggest a delirium-specific mechanism for atrophy, independent of dementia.