Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank

Abstract

Background: Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI.

Methods: For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8 years before the baseline evaluation.

Findings: Of 502 412 participants in the UK Biobank study, 492 802 participants were eligible for inclusion in this study, of whom 46 706 underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273 ms, fluid intelligence score decreased by 0·057 correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95 to 0·97]), and numeric memory maximum correct matches decreased by 0·025 in fully adjusted models. Surgeries were associated with smaller hippocampal volume (β=-5·76 mm³ [-7·89 to -3·64]) and greater white matter hyperintensities volume (β=100·02 mm³ [66·17 to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex.

Interpretation: This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures.

Funding: The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

Figure 1:. Study profile and timeline

(A) Study profile. (B) Study timeline. DKT=Desikan–Killiany–Tourville. IPAQ=International Physical Activity Questionnaire. SDST=symbol digit substitution test. TMTA=trail making test A (numeric). TMTB=trail making test B (alphanumeric).

Figure 1:. Study profile and timeline

(A) Study profile. (B) Study timeline. DKT=Desikan–Killiany–Tourville. IPAQ=International Physical Activity Questionnaire. SDST=symbol digit substitution test. TMTA=trail making test A (numeric). TMTB=trail making test B (alphanumeric).

Figure 2:. Actual and predicted values from fully adjusted models showing the association of cumulative surgeries with primary cognitive outcomes at specific ages

(A) Reaction time. (B) Fluid intelligence. (C) Numeric memory. All analyses include instance 0, instance 2, and instance 3 data. All linear mixed effects models were fully adjusted for cognitive outcome ~ cumulative surgeries + cumulative stroke admissions + cumulative other medical admissions + baseline age + baseline age² normalised + time × deprivation + female sex + education + BMI + BMI² normalised + smoking + depression + alcohol consumption + physical activity + hypertension + diabetes + solid tumour + (1|participant). Quadratic terms were normalised by variable²/1000. Interaction for surgeries × other medical admissions is included in the reaction time and fluid intelligence fully adjusted models. Linear smoothing uses the formula y ~ x + I(x²).

Figure 3:. Brain maps of associations of DKT cortical regions with surgeries (β coefficients)

DKT=Desikan–Killiany–Tourville.