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

Abstract

Introduction The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. Methods A total of 1354 dementia‐ and kidney disease‐free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2–9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow‐up, 453 participants died and underwent autopsies for neuropathological assessment. Results Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. Discussion Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. Highlights Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

Association of Kidney Function With Dementia and Structural Brain Differences: A Large Population-Based Cohort Study

“…Second, the diagnoses recorded in the patient registry have high specificity but relatively low sensitivity (the positive predictive value of dementia cases is 80%–87% in the UK Biobank) ( 47 ), and this might also lead to the underestimation of the association between kidney function and dementia risk. However, the observed association in this study is comparable with that reported in our previous study, in which dementia was diagnosed based on yearly follow-up examinations by a physician (eGFR ≥ 60 vs <60; HR = 1.67, 95%CI: 1.14 to 2.44) ( 48 ). Therefore, the underestimation may not be substantial.…”

Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant

“…Autopsy and amyloid PET studies indicate that despite higher prevalence of cognitive impairment, patients with CKD do not have a higher prevalence of typical cerebral amyloid and tau pathology seen in AD. 10 , 39 , 40 CKD is however associated with cerebral amyloid angiopathy 40 which in theory could contribute to elevated Aβ levels in CKD. While it is common for patients with CKD to get diagnosed with AD, this diagnosis is generally made clinically without confirmation of the presence of cerebral amyloid plaques.…”

Looking at the periphery—new hypothesis to look for new targets for Alzheimer’s disease therapy

“…However, recent studies have indicated that tau could be present in kidney, playing a role in the morphology of podocyte architecture [76]. Also, in some tauopathies, like frontotemporal dementia, some patients report urinary incontinence [77] and, more recently, the association of impaired kidney functions with dementia and brain pathologies has been indicated [78,79]. Curiously, AD patients with chronic kidney disease (CKD) treated with cholinesterase inhibitors showed a lower risk of CKD [80].…”