AbstractBackgroundPoorer kidney function could represent a novel modifiable risk factor for dementia, however previous findings are inconclusive. In the current study, we utilized a large population‐based cohort with long follow‐up to investigate whether glomerular filtration rate (GFR), an indicator of kidney function, and albuminuria, an indicator of kidney damage, were associated with an increased risk of all‐cause dementia.MethodThe sample consisted of 202,702 UK Biobank participants aged ≥60 years and free from dementia and end‐stage kidney disease at baseline between 2006‐2010. Estimated GFR was derived from serum creatinine and cystatin C (eGFRcr‐cys) and categorized as ≥90 (normal/high function), 60‐89 (mildly decreased function) and <60 ml/min/1.73m2 (moderately/severely decreased function). Albuminuria was defined using the urinary albumin to creatinine ratio (ACR). ACR was categorized into <3 (normal/mildly increased), 3‐30 (moderately increased), and >300 (severely increased) mg/mmol. Incident dementia was determined through cohort‐wide linkage to hospital and death records. The associations were assessed using Cox proportional‐hazard models adjusted for age, sex, ethnicity, socioeconomic status, education, household income, country, smoking status, alcohol intake, body mass index, hypertension, diabetes, and APOE‐ε4 allele status.ResultOver 15 years of follow‐up, 6,042 participants developed incident dementia. The fully‐adjusted Hazard Ratios (HR) were 1.00 (95% Confidence Interval [CI] 0.94‐1.06) and 1.42 (95% CI 1.28‐1.58) for eGFRcr‐cys 60‐89 and <60 respectively, compared to ≥90 ml/min/1.73m2. Moderately/severely decreased eGFRcr‐cys remained associated with incident dementia after restricting to participants with more than 10 years of follow‐up (HR = 1.33, 95% CI 1.13‐1.56). The HRs for moderate and severely increased ACR were 1.16 (95% CI 1.07‐1.26) and 2.24 (95% CI 1.79‐2.80), respectively, compared to normal/mildly increased ACR (<3mg/mmol). Dose‐response associations were observed when combining eGFRcr‐cys and ACR, with those in the severest eGFRcr‐cys and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34‐9.43).ConclusionKidney dysfunction and albuminuria were associated with a higher risk of incident all‐cause dementia. These findings provide additional evidence that kidney dysfunction could be a potential modifiable risk factor for dementia or target for identifying those at high risk of the condition.