Clinical Significance of Fronto-Temporal Gray Matter Atrophy in Executive Dysfunction in Patients with Chronic Kidney Disease: The VCOHP Study

<div><p>Background & Objectives</p><p>It is well known that cognitive impairment in patients with chronic kidney disease (CKD) is characterized by executive dysfunction, rather than memory dysfunction, although the precise mechanism of this remains to be elucidated. The purpose of the present study is to examine the correlation between gray matter volume (GMV) and executive function in CKD patients.</p><p>Design, Setting, Participants, Measurements</p><p>This cross-sectional study recruited 95 patients with non-dialysis-dependent CKD (NDD-CKD) with no history of cerebrovascular disease, who underwent brain magnetic resonance imaging (MRI) and Trail Making Test (TMT) in the VCOHP Study. The subjects underwent brain MRI and TMT part A (TMT-A) and part B (TMT-B). The segmentation algorithm from Statistical Parametric Mapping 8 software was applied to every T1-weighted MRI scan to extract tissue maps corresponding to gray matter, white matter, and cerebrospinal fluid. GMV was normalized by dividing by the total intracranial volume, calculated by adding GMV, white matter volume, and cerebrospinal fluid space volume. Then, normalized whole-brain GMV was divided into four categories of brain lobes; frontal, parietal, temporal, and occipital. We assessed the correlation between normalized GMV and TMT using multivariable regression analysis.</p><p>Results</p><p>Normalized whole-brain GMV was significantly inversely correlated to the scores of TMT-A, TMT-B, and ΔTMT (TMT-B minus TMT-A). These correlations remained significant even after adjusting for relevant confounding factors. Normalized frontal and temporal GMV, but not parietal and occipital GMV, were significantly inversely correlated with TMT-A, TMT-B, and ΔTMT using multivariable regression analysis.</p><p>Conclusions</p><p>The present study demonstrates the correlation between normalized GMV, especially in the frontal and temporal lobes, and executive function, suggesting that fronto-temporal gray matter atrophy might contribute to executive dysfunction in NDD-CKD.</p></div

Univariable and Multivariable-Adjusted Regression Analyses of Correlation between Normalized Regional GMV and TMT.

<p>Abbreviations: GMV, gray matter volume; TMT, Trail Making Test.</p

Univariable and Multivariable-Adjusted Regression Analyses of Correlation between Normalized Whole-Brain GMV and TMT Scores in Participants Stratified by eGFR (<45 vs. ≥45 mL/min/1.73 m²).

<p>Model I: Multivariable analysis adjusted for sex and age. Model II: Model I + diabetes mellitus, estimated glomerular filtration rate, and education. Model III: Model II + systolic blood pressure, smoking habits, drinking habits, hemoglobin, previous history of cardiovascular disease, and log-transformed urinary protein to creatinine ratio. Abbreviations: eGFR, estimated glomerular filtration rate; TMT, Trail Making Test.</p

Univariable and Multivariable-Adjusted Regression Analyses of Correlation between Normalized Whole-Brain GMV and TMT Scores in All Participants.

<p>Model I: Multivariable analysis adjusted for sex and age. Model II: Model I + diabetes mellitus, estimated glomerular filtration rate, and education. Model III: Model II + systolic blood pressure, smoking habits, drinking habits, hemoglobin, previous history of cardiovascular disease, and log-transformed urinary protein to creatinine ratio. Abbreviations: TMT, Trail Making Test.</p

Univariable and Multivariable-Adjusted Regression Analyses of Correlation between Normalized Whole-Brain GMV and TMT Scores in Participants Stratified by Age (<65 vs. ≥65 years).

<p>Model I: Multivariable analysis adjusted for sex and age. Model II: Model I + diabetes mellitus, estimated glomerular filtration rate, and education. Model III: Model II + systolic blood pressure, smoking habits, drinking habits, hemoglobin, previous history of cardiovascular disease, and log-transformed urinary protein to creatinine ratio. Abbreviation: GMV, gray matter volume; TMT, Trail Making Test.</p

Univariable and Multivariable-Adjusted Regression Analyses for Normalized GMV.

<p>Abbreviations: CRP, C-reactive protein; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GMV, gray matter volume; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NT-proBNP, N-terminal pro-brain natriuretic peptide; PTH, parathyroid hormone; RAAS, renin-angiotensin-aldosterone system; UPCR, urinary protein to creatinine ratio.</p

Correlations between normalized white matter volume (WMV) and the scores (times in seconds) of Trail Making Test (TMT).

<p>No correlations are found between normalized WMV and each score of TMT-A (A), TMT-B (B), and ΔTMT (C).</p

Clinical Characteristics and Laboratory Data of All Participants According to CKD Stages.

<p>Values for categorical variables are given as number (percentage); values for continuous variables are given as mean ± standard deviation or median (interquartile range). Abbreviations: eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NT-proBNP, N-terminal pro-brain natriuretic peptide; PTH, parathyroid hormone; RAAS, renin-angiotensin-aldosterone system; UPCR, urinary protein to creatinine ratio.</p

Correlations between age and normalized gray matter volume (GMV) and normalized white matter volume (WMV).

<p>A significant inverse correlation is found between age and normalized GMV (A), while no correlation is found between age and normalized WMV (B).</p

TMT Scores and MRI measurements of All Participants According to CKD Stages.

<p>Abbreviations: CSFV, cerebrospinal fluid volume; GMV, gray matter volume; TICV, total intracranial volume; TMT, Trail Making Test; WMV, white matter volume.</p