Evaluating the effect of kidney function on brain volumes and dementia risk in the UK Biobank

Abstract

Objective: To investigate the association between kidney function with the risk of dementia and brain volumes.

Methods: A total of 452,996 UK Biobank participants with calculated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) were included. We utilized Cox proportional hazards regression models and restricted cubic spline analyses to examine the relationships between kidney function and the risk of all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Additionally, we explored the correlations between kidney function and brain magnetic resonance indicators among 40,380 participants.

Results: During a median follow-up of 12 years, 5,258 incident ACD cases were identified. The deterioration of kidney function was associated with an increased risk of ACD. When compared to eGFR ≥ 90 ml/min/1.73 m², the highest risk increase was evident for eGFRcre < 30 ml/min/1.73 m² (adjusted HR = 2.372, 95% CI: 1.444-3.897, P < 0.001), with eGFRcys showing greater significance (adjusted HR = 3.045, 95% CI: 2.212-4.191, P < 0.001), especially in relation to AD. Compared to the ACR level in the range of 3-30 mg/mmol, the category of > 30 mg/mmol was associated with an increased risk of ACD (adjusted HR = 1.720, 95% CI: 1.350-2.190, P < 0.001). Moreover, the decline in kidney function was associated with the total brain volume atrophy and reduction in certain subcortical areas.

Conclusions: Our study indicates that diminished kidney function, as evidenced by a drop in eGFR and aggravated proteinuria, elevates dementia risk. Associated brain structural changes further underpin this connection from a neuro-pathophysiological perspective.

Keywords: Albuminuria; Brain volume; Dementia; Glomerular filtration rate; Kidney function.