Association of kidney function with dementia and structural brain differences: a large population‐based cohort study
Shuqi Wang, Jiao Wang, Abigail Dove, Jie Guo, Yuyang Miao, Xiuying Qi, Weili Xu- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
The association between kidney function (KF) and dementia risk and the mechanisms underlying this relationship remain unclear. We aimed to examine the association of impaired KF with dementia and structural brain differences on magnetic resonance imaging (MRI).
Method
Within the UK biobank, 191,970 dementia‐free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) using the Chronic Kidney Disease Epidemiology Collaboration equation. KF was categorized as normal (eGFR ≥ 90), mildly impaired (60 £ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self‐reported medical history and medical records. During the follow‐up, a subsample of 12,637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. Data were analyzed using Cox regression, Laplace regression, and linear regression.
Result
Of all participants, 122,463 (63.8%) had mildly impaired KF and 8,670 (4.5%) had moderate to severely impaired KF at baseline. Over the follow‐up (median [interquartile range]: 12.8 [11.9‐13.5] years), 5,327 (2.8%) participants developed dementia. In multi‐adjusted Cox regression, eGFR was dose‐dependently associated with dementia (per 1‐standard‐deviation decrease in eGFR; hazard ratio [HR] 95% confidence interval [CI]: 1.10 [1.07‐1.14]). Compared to normal KF, there was an increased risk of dementia with moderate to severely impaired KF (HR 1.53, 95% CI 1.32‐1.76) but not mildly impaired KF. In Laplace regression, dementia onset among people with moderate to severely impaired KF occurred 1.53 (95% CI: 0.98–2.08) years earlier than those with normal KF. Moderate to severely impaired KF was related to significantly lower gray matter volume (β = ‐0.11, 95% CI: ‐0.19– ‐0.03), but not to other brain MRI measures.
Conclusion
Impaired KF is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the KF‐dementia association.