Chronic Kidney Disease and Incident Dementia: The HUNT Study

Previous studies have reported associations between chronic kidney disease (CKD) and an increase in risk for cardiovascular disease and worse cognitive performance. The risk factors for CKD and dementia share similar factors including hypertension, diabetes mellitus, stroke, myocardial infarction, and hyperlipidemia. However, according to Jessica Mira Gabin, MD, and colleagues, there are few data on the association between CKD and dementia. Epidemiological studies have found an association between albuminuria and low glomerular filtration rate (GFR) and Alzheimer’s disease (AD) and vascular dementia (VaD), but the findings have been mixed and no associations have been published.

Moderately increased albuminuria (formerly called microalbuminuria [MA]), is an early risk marker of renal endothelial dysfunction. The importance of MA in cardiovascular disease is well documented. The current population-based cohort study was designed to use baseline albumin creatinine ratio (ACR) to examine the association between MA and the risk for incident AD, VaD, and mixed AD/VaD. The researchers also examined estimated GFR (eGFR) to determine if the association differed across samples in varying stages of CKD. Results were reported online in BMC Nephrology [doi.org/10.1186/s12882-019-1425-8].

The HUNT 2 survey (1995-1997) conducted in Nord-Trøndelag County, Norway, included 64,978 participants. Following application of exclusion criteria, the current study included 48,508 participants. Of those, 668 were diagnosed with dementia and 47,840 were not diagnosed with dementia. A total of 7606 died during the study period.

Mean age of the study sample was 49.5 years and mean eGFR was 78.8 mL/min/1.73 m2. Individuals diagnosed with dementia were older, had reduced eGFR, higher systolic and diastolic blood pressure, and higher prevalence of self-reported cardiovascular disease. Hazard regression models did not reveal any statistically significant association between eGFR and dementia or its subgroups. There were interactions between age and eGFR in dementia and its subgroups.

MA Substudy

The MA substudy included HUNT 2 participants who self-reported diabetes mellitus and/or treated hypertension, and a randomly selected non-diabetic/non-treated hypertensive sample. Those participants were asked to deliver three urine samples from three consecutive days.

Subgroups were created to examine those diagnosed with dementia and diabetes or treated for hypertension (n=184) and those diagnosed with dementia and without diabetes or treatment for hypertension (n=30). In addition, 5135 participants without dementia and with diabetes or treatment for hypertension, and 1675 controls who were without diabetes and were not treated for dementia were included in the analyses (total number included in the analyses: 7024).

There were no differences across quartiles of the total sample. Those diagnosed with dementia were older, had higher systolic and diastolic blood pressure, lower renal function, and higher cholesterol.

In analyses adjusted by age and other variables at different albumin creatinine ratio (ACR) levels expressed in quartiles, there was a positive association between increasing ACR and combined AD/VaD. ACR in the fourth quartile (≥1.78 mg/mmol) was associated with increased hazard ratio of VaD (3.97; 95% confidence interval, 1.12-14.07) compared with ACR in the first quartile (<.53 mg/mmol). There were no sex interactions or age interactions between ACR and total dementia, combined AD/VaD, mixed Ad/VaD, or VaD in crude analyses.

The researchers cited some limitations to the study, including competing risk from death and other causes in a population of older adults; lack of access to a national prescription registry that would have provided details regarding types of medications taken by the participants; and the small number of participants with CKD.

In conclusion, the researchers said, “Our results strengthen the hypothesis that vascular mechanisms may affect both kidney and brain as an association between moderately increased albuminuria, VaD, and combined AD/VaD was found. However, eGFR was not significantly associated with dementia independent of diabetes mellitus or hypertension.”

Takeaway Points

  1. A study in Norway was designed to examine the association between estimated glomerular filtration rate (eGFR) and moderately increased albuminuria (MA) and dementia and subtypes of dementia (Alzheimer’s disease (AD), vascular dementia (VaD), and combined AD/VaD.
  2. There was an association between MA and VaD and combined AD/VaD.
  3. There was no significant association between eGFR and dementia independent of diabetes mellitus or hypertension.