Association of kidney function with dementia and brain pathologies: A community‐based cohort study

Abstract

AbstractBackgroundKidney function has been linked to cognitive function, but its relation to dementia and mechanisms underlying this relation remains unclear. We aimed to examine the association of impaired kidney function with dementia and brain pathologies.MethodWithin Rush Memory and Aging Project, 1380 dementia‐free subjects (75.22% female; mean age: 79.42±7.61 years) at baseline were followed for up to 22 years. Blood samples were taken at baseline and serum creatinine was measured to calculate estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. Kidney function dichotomized as normal (eGFR ≥ 60 mL/min/1.73 m2) or impaired (eGFR <60 mL/min/1.73 m2). Dementia, including Alzheimer’s dementia, was diagnosed following international criteria. During the follow‐up, 469 participants died and underwent autopsies for neuropathological assessment (including Alzheimer’s disease [AD], vascular, and other brain pathologies). Data were analyzed using Cox regression, Laplace regression, and logistic regression.ResultAt baseline, 895 (64.86%) participants with normal kidney function and 485 (35.14%) with impaired. Over follow‐up (median [interquartile range]: 5 [2–9] years), 300 (21.74%) participants developed dementia, including 273 (19.78%) with Alzheimer’s dementia. In multi‐adjusted Cox regression, lower eGFR was does‐dependently associated with higher dementia risk (hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 1.01–1.02, P = 0.003) and Alzheimer’s dementia risk (HR = 1.01, 95% CI: 1.00‐1.02, P = 0.002). Compared to normal kidney function, impaired kidney function was associated with a greater risk of dementia (HR = 1.49, 95% CI: 1.16–1.91) and Alzheimer’s dementia (HR = 1.45, 95% CI: 1.12–1.89). The median time to the development of dementia or Alzheimer’s dementia was 2.48 (95% CI: 0.36–3.03) or 2.56 (95% CI: 0.37–2.79) years shorter in people with impaired vs. normal kidney function, respectively. In brain pathology analysis, impaired kidney function was significantly related to higher burdens of cerebral amyloid angiopathy (odds ratio = 2.03, 95% CI: 1.23–3.35).ConclusionImpaired kidney function is associated with an increased risk of dementia and Alzheimer’s dementia. Vascular mechanisms may underlie this association.