Structural and functional assessment of the brain in European Americans with mild-to-moderate kidney disease: Diabetes Heart Study-MIND.
BACKGROUND
Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs).


METHODS
A total of 478 EAs with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2) and urine albumin:creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education.


RESULTS
Participants were 55.2% female, 78.2% had T2D; mean ± SD age 67.6 ± 9.0 years, T2D duration 16.4 ± 6.5 years, eGFR 92.0 ± 22.3 mL/min/1.73 m(2) and UACR 23.8 ± 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (β): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (β: -1.0, P = 0.03) and UACR and normalized TWMLV (β: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing.


CONCLUSIONS
In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.
Internal Medicine-Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Mariana
M
Murea
Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Fang-Chi
FC
Hsu
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Amanda J
AJ
Cox
Internal Medicine-Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Christina E
CE
Hugenschmidt
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Jianzhao
J
Xu
Molecular Genetics and Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Jeremy N
JN
Adams
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Laura M
LM
Raffield
Radiologic Sciences and Advanced NeuroScience Imaging (ANSIR) Laboratory, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Christopher T
CT
Whitlow
Radiologic Sciences and Advanced NeuroScience Imaging (ANSIR) Laboratory, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Joseph A
JA
Maldjian
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Donald W
DW
Bowden
Internal Medicine-Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Barry I
BI
Freedman
D000419:Albuminuria / Q000150:complications*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D048909:Diabetes Complications / Q000209:etiology* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007677:Kidney Function Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D014481:United States; D044465:White People
D006442:Glycated Hemoglobin
albuminuria; brain; cognitive function; kidney disease; magnetic resonance imaging