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

Jiménez-Baladó, Joan; Riba‐Llena, Iolanda; Pizarro, Jesús; Palasí, Antoni; Peñalba, Anna; Ramírez, Clara; Maisterra, Olga; Espinel, Eugènia; Ramos, Natália; Pujadas, Francesc; Serón, Daniel; Delgado, Pilar

doi:10.1016/j.jns.2019.116635

Cited by 19 publications

(14 citation statements)

References 31 publications

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“…The level of blood glucose was significantly higher in the MCI group, which reflected the impairment in glucose metabolism of the participants, which is highly correlated with cognitive impairment 28 . Several studies revealed that a reduction in albumin/globulin ratio and eGFR were associated with cognitive dysfunction [29][30][31] . These data indicated that our EGAT participants with MCI were older, and had higher BP and WHR, than those in normal cognition group.…”

Section: Discussionmentioning

confidence: 99%

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population

Apaijai

Sriwichaiin

Phrommintikul

et al. 2020

Sci Rep

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Cognitive impairment is commonly found in the elderly population. Evidence suggests that mitochondrial function in lymphocytes are potential biomarkers in the progression of neurodegeneration, as peripheral mitochondrial function is associated with mild cognitive impairment (MCI) in the elderly population. Therefore, we hypothesize that impaired mitochondrial ATP production and oxidative stress in peripheral blood mononuclear cells (PBMCs) are associated with cognitive impairment in the elderly population. Data were collected from 897 participants from the EGAT (The Electricity Generating Authority of Thailand) cohort. The participants were classified to be in the normal cognition group (n = 428) or mild cognitive impairment group (n = 469), according to their MoCA score. The association of mitochondrial function and cognitive status was analyzed by binary logistic regression analysis. MCI participants had higher age, systolic blood pressure, waist/hip ratio, and lower plasma high- and low-density lipoprotein cholesterol levels, when compared to the normal cognition group. In addition, estimated glomerular filtration rate were lower in the MCI group than those in the normal cognition group. Collectively, MCI is associated with mitochondrial dysfunction in PBMCs as indicated by decreasing mitochondrial ATP production, increasing proton leak, and oxidative stress, in the elderly population, independently of the possible confounding factors in this study.

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Section: Discussionmentioning

confidence: 99%

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population

Apaijai

Sriwichaiin

Phrommintikul

et al. 2020

Sci Rep

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“…Nevertheless, few studies [ 11 , 31 ] have determined whether albuminuria is persistent or disappears during follow-up as a result of treatments or changes in lifestyle [ 36 ]. Therefore, future longitudinal studies with multiple determinations of albuminuria are needed to clarify this point.…”

Section: Resultsmentioning

confidence: 99%

“…Albuminuria represents a marker of microvascular disease preceding the loss of kidney function, accumulation of cSVD lesions and stroke [ 36 , 63 , 64 , 65 ]. After BBB breakdown occurs, several mechanisms may explain the connection between UACR and cognitive impairment, including an exacerbated inflammatory response.…”

Section: Resultsmentioning

confidence: 99%

Diabetes, Albuminuria and the Kidney—Brain Axis

Ariton

Jiménez-Baladó

Maisterra

et al. 2021

JCM

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Cognitive decline and kidney disease are significant public health problems that share similar characteristics and risk factors. The pathophysiology of the kidney–brain axis is not completely understood, and studies analysing the relationship between the biomarkers of kidney damage and cognitive impairment show different results. This article focuses on the epidemiological and clinical aspects concerning the association of albuminuria, a marker for endothelial dysfunction and microvascular disease, and cognitive impairment in patients with chronic kidney disease, diabetic kidney disease and end-stage kidney disease. Most studies show a positive relationship between albuminuria and cognitive impairment in all groups, but evidence in type 2 diabetes (T2D) patients is limited. We briefly discuss the mechanisms underlying these associations, such as damage to the microvascular circulation, leading to hypoperfusion and blood pressure fluctuations, as well as increased inflammation and oxidative stress, both in the brain and in the kidneys. Further clinical and epidemiological studies developed to understand the interplay between the kidneys and brain diseases will hopefully lead to a reduction in cognitive impairment in these patients.

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“…In this context, the study of blood biomarkers might contribute to the achievement of two objectives: increasing the knowledge of the potential causes of WMH, and improving the diagnosis. Previous research has found WMH volume correlated with markers of endothelial dysfunction 11 – 14 , inflammation 15 , 16 , kidney function 17 , lipid metabolism 18 , and hemostasis 19 . However, most of these studies had cross-sectional designs, so it was not possible to determine whether these biological processes were involved in the progression of WMH.…”

Section: Introductionmentioning

confidence: 96%

New candidate blood biomarkers potentially associated with white matter hyperintensities progression

Jiménez-Baladó

Pizarro

Riba‐Llena

et al. 2021

Sci Rep

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We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50–70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.

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

Cited by 19 publications

References 31 publications

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population

Diabetes, Albuminuria and the Kidney—Brain Axis

New candidate blood biomarkers potentially associated with white matter hyperintensities progression

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