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

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