Lower glomerular filtration rate associated with white matter hyperintensities more in vascular dementia than in Alzheimer's disease.

Abstract

To the Editor: White matter hyperintensities (WMHs) from cerebral small vessel disease (SVD) can indicate greater risk of stroke and dementia. Aging and hypertension are major risk factors for cerebral SVD, but these fail to account for all of the risk. Chronic kidney disease (CKD), defined according to estimated glomerular filtration rate (eGFR), is widely recognized as an independent risk factor for stroke and subclinical vascular diseases, such as SVD.1 Moreover, recent research has supported a causal role of inflammation, endothelial dysfunction, and oxidative stress in the development of vascular disease.2 These processes are all characteristic of CKD3 and may also be found in vascular dementia (VaD) and Alzheimer's disease (AD).4 Data regarding the role of low eGFR in the development of WMHs in AD and VaD are limited.5 It was hypothesized that lower eGFR would be more strongly associated with WMHs in VaD than AD, independent of vascular risk factors. This study formed part of the ongoing Clinical Research Center for Dementia of South Korea Study (CREDOS), a large, prospective, hospital-based cohort study designed to assess the occurrence of and risk factors for cognitive disorders, established in November 2005. Further information regarding CREDOS has been previously published.6 Data from 952 CREDOS participants with measurements of eGFR, hemoglobin, and albumin were retrospectively analyzed. All participants had a clinical interview and blood test on the same day. All blood parameters were analyzed according to the standard protocols of the biochemistry laboratories that participated in the study, which operate under a rigorous quality control program. Kidney function was indicated according to eGFR, which was calculated in mL/min per 1.73 m2 using the simplified Modification of Diet in Renal Disease equation (186.3 × (serum creatinine)−1.154 × age−0.203, multiplied by 0.742 for women).7 Anemia was defined according to World Health Organization criteria as hemoglobin concentrations less than 12 g/dL for women and 13 g/dL for men.8 A standardized neuropsychological battery, the Seoul Neuropsychological Screening Battery—Dementia version, was used to assess all participants. Magnetic resonance imaging (MRI) was conducted in accordance with an acquisition protocol developed for CREDOS. MRI scans included transaxial T2, T1-weighted, gradient-echo, fluid-attenuated inversion recovery (FLAIR), and coronal T1-weighted images. The severity of WMHs was evaluated according to modified Fazekas9 and Scheltens10 criteria, using the T2 axial or FLAIR images. WMHs were examined separately in the periventricular white matter and deep white matter. Logistic regression analysis was conducted in individuals with normal cognitive function, mild cognitive impairment (MCI), AD, and VaD to evaluate the effect of eGFR on severity of WMHs. Age, sex, history of hypertension, diabetes mellitus, hyperlipidemia, and ischemic heart disease were included as covariates. Of 952 older adults, 162 had normal cognitive function, 237 had MCI, 330 had AD, and 224 had VaD. The prevalence of hypertension and stroke was higher in participants with VaD. Logistic regression analysis indicated that the association between age, hypertension, and moderate WMHs was statistically significant in participants with normal cognitive function. Multivariate logistic regression analysis showed a significant association between hypoalbuminemia and moderate WMHs after adjustment for age, sex, and cardiovascular risk factors in participants with MCI and AD (Table 1). The association between eGFR and WMHs in participants with VaD was significant but was attenuated when adjusting for vascular risk factors. Vascular risk factors such as hypertension, dietary fat intake, high cholesterol, and obesity have emerged as important influences on the risk of VaD and AD, but there is little evidence to support the view that these vascular risk factors have the same influence on WMHs in both types of dementia. The present study provided an opportunity to examine the relationship between WMHs, eGFR, and hypoalbuminemia in AD and VaD and revealed that low eGFR was associated more strongly with WMHs in VaD than with MCI or AD. Hypoalbuminemia was also associated with WMHs in MCI and AD. SVD is an important pathophysiological mechanism in dementia but does not lend itself to categorical diagnostic labels. Hypoalbuminemia might be useful for differentiating the influence of SVD on dementia. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Hong, Son, Lee: study concept, design, interpretation of data, statistical analysis, writing of manuscript. Na, Seo, Kim: acquisition of subjects, data collection, endpoint adjudication, interpretation of data, statistical analysis. Choi: study coordinator, study concept, endpoint adjudication, interpretation of data. Oh: study concept, interpretation of data. Sponsor's Role: None.