Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (β = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (β = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Jiménez-Balado J ，Riba-Llena I ，Pizarro J ，Palasí A ，Penalba A ，Ramírez C ，Maisterra O ，Espinel E ，Ramos N ，Pujadas F ，Serón D ，Delgado P ... -  《-》

Microalbuminuria and the Combination of MRI Markers of Cerebral Small Vessel Disease.

Kidney function has been related to the presence of individual markers of cerebral small vessel disease (CSVD), as lacunes, white matter hyperintensities (WMH) or microbleeds. We aimed at studying the relationship of kidney dysfunction with the combination of several markers of CSVD. Subjects are those included in the ISSYS cohort (Investigating Silent Strokes in hypertensives: a magnetic resonance imaging study). A scale ranging from 0 to 4 points was applied based on the presence (one point each) of lacunes, deep microbleeds, moderate to extensive basal ganglia enlarged perivascular spaces (EPVS), and periventricular or deep WMH. We determined the creatinine-based glomerular filtration rate and the urinary albumin-to-creatinine ratio (UACR) as markers of kidney function and studied their association with the scale of CSVD in univariate and ordinal logistic regression analyses. Among the 975 patients included, 28.2% presented one or more CSVD markers, being the most prevalent marker (either alone or in combination) basal ganglia EPVS. The UACR was elevated at increasing the scores of the CSVD scale and remained as independent predictor of the combination of markers (common OR per natural log unit increase in UACR: 1.23, 1.07-1.41) after controlling per age, gender, cardiovascular risk, antihypertensive treatment and hypertension duration. In contrast, no associations were found between the CSVD scores and the creatinine-based estimated glomerular filtration rate. A significant proportion of stroke-free hypertensives present at least one imaging marker of CSVD. UACR but not creatinine-based glomerular filtration rate is associated with the combination of markers of CSVD.

Vilar-Bergua A ，Riba-Llena I ，Ramos N ，Mundet X ，Espinel E ，López-Rueda A ，Ostos E ，Seron D ，Montaner J ，Delgado P ... -  《-》

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Jiménez-Balado J ，Riba-Llena I ，Abril O ，Garde E ，Penalba A ，Ostos E ，Maisterra O ，Montaner J ，Noviembre M ，Mundet X ，Ventura O ，Pizarro J ，Delgado P ... -  《-》

The AGES-Reykjavik Study suggests that change in kidney measures is associated with subclinical brain pathology in older community-dwelling persons.

Decreased glomerular filtration rate (GFR) and albuminuria may be accompanied by brain pathology. Here we investigated whether changes in these kidney measures are linked to development of new MRI-detected infarcts and microbleeds, and progression of white matter hyperintensity volume. The study included 2671 participants from the population-based AGES-Reykjavik Study (mean age 75, 58.7% women). GFR was estimated from serum creatinine, and albuminuria was assessed by urinary albumin-to-creatinine ratio. Brain MRI was acquired at baseline (2002-2006) and 5 years later (2007-2011). New MRI-detected infarcts and microbleeds were counted on the follow-up scans. White matter hyperintensity progression was estimated as percent change in white matter hyperintensity volumes between the two exams. Participants with a large eGFR decline (over 3 ml/min/1.73m2 per year) had more incident subcortical infarcts (odds ratio 1.53; 95% confidence interval 1.05, 2.22), and more marked progression of white matter hyperintensity volume (difference: 8%; 95% confidence interval: 4%, 12%), compared to participants without a large decline. Participants with incident albuminuria (over 30 mg/g) had 21% more white matter hyperintensity volume progression (95% confidence interval: 14%, 29%) and 1.86 higher odds of developing new deep microbleeds (95% confidence interval 1.16, 2.98), compared to participants without incident albuminuria. The findings were independent of cardiovascular risk factors. Changes in kidney measures were not associated with occurrence of cortical infarcts. Thus, larger changes in eGFR and albuminuria are associated with increased risk for developing manifestations of cerebral small vessel disease. Individuals with larger changes in these kidney measures should be considered as a high risk population for accelerated brain pathology.

Sedaghat S ，Ding J ，Eiriksdottir G ，van Buchem MA ，Sigurdsson S ，Ikram MA ，Meirelles O ，Gudnason V ，Levey AS ，Launer LJ ... -  《-》

Kidney Dysfunction is Associated with a High Burden of Cerebral Small Vessel Disease in Primary Intracerebral Hemorrhage.

To investigate the association of kidney function with the total burden of Cerebral Small Vessel Disease (CSVD) in primary Intracerebral Hemorrhage (pICH). Cerebral magnetic resonance imagings of consecutively enrolled pICH patients were reviewed to assess for lacunes, White Matter Hyperintensity (WMH), Cerebral Microbleeds (CMBs) and Enlarged Perivascular Spaces (EPVS). Minor refinements to the CSVD score, namely modified CSVD score 1 and 2, were made by incorporating different weightings of CSVD markers. Kidney function was assessed using the estimated Glomerular Filtration Rate (eGFR). We used ordinal regression analysis to assess the association of kidney function with the CSVD score and modified scores. In the 108 patients included, the presence of lacunes, CMBs, MWH and basal ganglia EPVS>10 was 27.8%, 67.6%, 47.2% and 35.2%, respectively. In multivariable ordinal regression, a decreasing eGFR value was associated with an increased CSVD score [Odds Ratio (OR) 0.978, 95% Confidence Interval (CI) 0.962 to 0.995, P=0.013], modified CSVD score 1 (OR 0.973, 95% CI 0.957 to 0.990, P=0.002) and 2 (OR 0.969, 95% CI 0.953 to 0.986, P<0.001). The link between eGFR and the total burden of CSVD was significant in strictly deep pICH (P=0.011 for CSVD score; P=0.001 for modified score 1 and 2), but not strictly lobar pICH in subgroup analysis. Low eGFR is associated with a high burden of CSVD in patients with deep pICH, but not lobar pICH. Future studies are warranted to assess whether low eGFR is a potential therapeutic target for preventing the progress of CSVD burden for deep pICH.

Xu M ，Zhang S ，Liu J ，Luo H ，Wu S ，Cheng Y ，Liu M ... -  《-》