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

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

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Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15606723 ◽

2015 ◽

Vol 36 (2) ◽

pp. 302-325 ◽

Cited By ~ 102

Author(s):

Leif Østergaard ◽

Thorbjørn S Engedal ◽

Fiona Moreton ◽

Mikkel B Hansen ◽

Joanna M Wardlaw ◽

...

Keyword(s):

Cognitive Decline ◽

Capillary Flow ◽

Small Vessel Disease ◽

Genetic Disorders ◽

The Elderly ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vascular Pathology ◽

Vessel Disease ◽

Capillary Dysfunction

Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline.

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

Cerebrovascular Diseases ◽

10.1159/000445168 ◽

2016 ◽

Vol 42 (1-2) ◽

pp. 66-72 ◽

Cited By ~ 7

Author(s):

Andrea Vilar-Bergua ◽

Iolanda Riba-Llena ◽

Natalia Ramos ◽

Xavier Mundet ◽

Eugenia Espinel ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Basal Ganglia ◽

Glomerular Filtration ◽

Kidney Function ◽

Filtration Rate ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2016.00301 ◽

2016 ◽

Vol 8 ◽

Cited By ~ 35

Author(s):

Renske Uiterwijk ◽

Robert J. van Oostenbrugge ◽

Marjolein Huijts ◽

Peter W. De Leeuw ◽

Abraham A. Kroon ◽

...

Keyword(s):

Executive Function ◽

Cognitive Decline ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Mri Score

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P4-286: CEREBRAL SMALL VESSEL DISEASE AND COGNITIVE DECLINE IN AN ASIAN MEMORY CLINIC POPULATION

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3955 ◽

2019 ◽

Vol 15 ◽

pp. P1395-P1396

Author(s):

Bibek Gyanwali ◽

Eddie Chong ◽

Xin Xu ◽

Narayanaswamy Venketasubramanian ◽

Christopher Chen ◽

...

Keyword(s):

Cognitive Decline ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Memory Clinic ◽

Vessel Disease ◽

Clinic Population

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TOTAL MRI BURDEN OF CEREBRAL SMALL-VESSEL DISEASE IS ASSOCIATED WITH COGNITIVE DECLINE AND AN INCREASED RISK OF DEMENTIA IN OLDER PEOPLE: THE AGES-REYKJAVIK STUDY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.084 ◽

2017 ◽

Vol 13 (7) ◽

pp. P211-P212

Author(s):

Jie Ding ◽

Sigurdur Sigurdsson ◽

Mark van Buchem ◽

Vilmundur Gudnason ◽

Lenore J. Launer

Keyword(s):

Older People ◽

Cognitive Decline ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

Increased Risk

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Cerebral Small Vessel Disease and Kidney Function Predict Long-Term Survival in Patients With Acute Stroke

Stroke ◽

10.1161/strokeaha.110.587352 ◽

2010 ◽

Vol 41 (9) ◽

pp. 1914-1920 ◽

Cited By ~ 21

Author(s):

Niku K.J. Oksala ◽

Tapani Salonen ◽

Timo Strandberg ◽

Anni Oksala ◽

Tarja Pohjasvaara ◽

...

Keyword(s):

Acute Stroke ◽

Kidney Function ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Term Survival ◽

Long Term Survival ◽

Vessel Disease

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Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

Translational Psychiatry ◽

10.1038/s41398-021-01495-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

O. K. L. Hamilton ◽

S. R. Cox ◽

J. A. Okely ◽

F. Conte ◽

L. Ballerini ◽

...

Keyword(s):

Cognitive Decline ◽

Cognitive Ability ◽

Birth Cohort ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

General Cognitive Ability ◽

Vessel Disease ◽

Lothian Birth Cohort

AbstractSlowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

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