Moderately increased albuminuria, chronic kidney disease and incident dementia: the HUNT study

Abstract

Background Epidemiologic studies has shown an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. This study examines the association between eGFR, MA with dementia and its subtypes: AD, VaD, a mixture of AD/VaD, and other dementias. Methods Data from the second wave of the HUNT 2 Study (1995–1997) were linked with a dementia register known as the Health and Memory Study (HMS) collected during 1995–2011 in Nord-Trøndelag County, Norway. Dementia was ascertained using World Health Organization’s ICD-10 criteria into subtypes: AD,VaD, mixed AD/VaD, and other dementia. eGFR and its association with dementia was examined in 48,508 participants of the HUNT Study, of which 668 were diagnosed with all-cause dementia. Association between MA and dementia were studied in a subset of 7024 participants, and 214 were diagnosed with all-cause dementia. Cox regression models were conducted analyzing the association between dementia and MA using albumin creatine ratio (ACR). Cox regression models and Fine-Gray models were used to examine the association between dementia and eGFR. Results A positive association was found between increasing ACR and dementia. ACR in the fourth quartile (> 1.78 mg/mmol) with increased hazard ratio of VaD, 3.97 (1.12 to 14.07), compared with ACR in the first quartile (<.53 mg/mmol). There was no association between eGFR and dementia or its subgroups. Conclusions Our results strengthens the hypothesis that vascular mechanisms may affect both kidney and brain as an association between MA and dementia was found. However, eGFR was not significantly associated with dementia independent of diabetes mellitus or hypertension. Electronic supplementary material The online version of this article (10.1186/s12882-019-1425-8) contains supplementary material, which is available to authorized users.

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese ― The Hisayama Study ―

“…[17][18][19][20][21] However, in these studies the extent of WMH was evaluated by semiquantitative methods, such A lbuminuria and reduced estimated glomerular filtration rate (eGFR) are components of chronic kidney disease (CKD), and both have been acknowledged as risk factors for stroke, dementia, and death. [1][2][3][4][5][6] The major causes of CKD include small vessel diseases in the kidney due to glomerular endothelium dysfunction. 7 Conversely, white matter hyperintensities (WMH) in the brain are a type of cerebral small vessel disease often observed on T2-weighted or fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) among the elderly and have been reported to be associated with an increased risk of the development of stroke, dementia, and death.…”

Diabetes, Albuminuria and the Kidney—Brain Axis

“…Over the past few years, despite a wide variability in the methodologies and outcome assessments, several studies have shown associations between albuminuria and the risk of developing cognitive impairment and dementia, as well as a correlation with imaging markers for cognitive decline. Moreover, a recent meta-analysis provided the same conclusions [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ] based on the results of population-based studies. Less is known about T2D specifically; however, because T2D patients suffer from both an increased risk of cognitive impairment and kidney disease [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ], elucidating the mechanisms of disease and exploring the interplay between the brain and kidney might potentially help to prevent cognitive impairment both in general and T2D populations.…”

“…Alzheimer’s disease (AD) is the most frequent subtype, corresponding to 60–80% of all cases, followed by vascular dementia (VaD), dementia with Lewy bodies (DLB) and other neurodegenerative dementias, including a mixture of the first two previous ones [ 35 ]. After a 16-year follow-up, Gabin et al [ 14 ] showed a positive association between the microalbuminuria and different subtypes of dementia, such as Alzheimer’s disease, vascular dementia, a mixture of AD/VaD and other dementias, including DLB and FTD. These researchers found a positive association between albuminuria and AD/VaD, with stronger associations for VaD (HR = 3.97) upon the subgroup analysis.…”

Mild-moderate CKD is not associated with cognitive impairment in older adults in the Alzheimer’s Disease Neuroimaging Initiative cohort

“…The Health ABC study [28] did not show an association between eGFR and cognition (odds ratio 1.10, 95% CI, 0.80 to 1.51) in participants >73 years supporting the results of our study. Similarly, the French 3C study [20], the Norwegian HUNT study [21] or the Australian Sydney Memory and Ageing Study [22] did not show an detrimental association between lower eGFR and cognitive decline or dementia.…”

“…In older adults, the association of eGFR and cognition remains contentious. While some studies report absence of cognitive impairment at eGFR of >30 mL/min/1.73 m 2 [19][20][21][22], others report incremental risk of cognitive impairment with declining eGFR [23][24][25]. Baseline differences in age and comorbidities or use of tests designed for screening and not detection of severity of cognitive impairment make the results difficult to interpret.…”