Design and methods of the NiCK study: neurocognitive assessment and magnetic resonance imaging analysis of children and young adults with chronic kidney disease.
BACKGROUND
Chronic kidney disease is strongly linked to neurocognitive deficits in adults and children, but the pathophysiologic processes leading to these deficits remain poorly understood. The NiCK study (Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease) seeks to address critical gaps in our understanding of the biological basis for neurologic abnormalities in chronic kidney disease. In this report, we describe the objectives, design, and methods of the NiCK study.


METHODS
The NiCK Study is a cross-sectional cohort study in which neurocognitive and neuroimaging phenotyping is performed in children and young adults, aged 8 to 25 years, with chronic kidney disease compared to healthy controls. Assessments include (1) comprehensive neurocognitive testing (using traditional and computerized methods); (2) detailed clinical phenotyping; and (3) multimodal magnetic resonance imaging (MRI) to assess brain structure (using T1-weighted MRI, T2-weighted MRI, and diffusion tensor imaging), functional connectivity (using functional MRI), and blood flow (using arterial spin labeled MRI). Primary analyses will examine group differences in neurocognitive testing and neuroimaging between subjects with chronic kidney disease and healthy controls. Mechanisms responsible for neurocognitive dysfunction resulting from kidney disease will be explored by examining associations between neurocognitive testing and regional changes in brain structure, functional connectivity, or blood flow. In addition, the neurologic impact of kidney disease comorbidities such as anemia and hypertension will be explored. We highlight aspects of our analytical approach that illustrate the challenges and opportunities posed by data of this scope.


CONCLUSIONS
The NiCK study provides a unique opportunity to address key questions about the biological basis of neurocognitive deficits in chronic kidney disease. Understanding these mechanisms could have great public health impact by guiding screening strategies, delivery of health information, and targeted treatment strategies for chronic kidney disease and its related comorbidities.
Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, USA. hartunge@email.chop.edu.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. hartunge@email.chop.edu.
Erum A
EA
Hartung
Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, USA. laneyn@email.chop.edu.
Nina
N
Laney
Biostatistics Core, Clinical and Translational Research Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA. kimj15@email.chop.edu.
Ji Young
JY
Kim
Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, USA. ruebnerr@email.chop.edu.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. ruebnerr@email.chop.edu.
Rebecca L
RL
Ruebner
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. detre@mail.med.upenn.edu.
John A
JA
Detre
Graduate Institute of Clinical Medicine and Imaging Research Center, College of Medicine, Taipei Medical University, Taipei, Taiwan. heatherusa2010@gmail.com.|Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan. heatherusa2010@gmail.com.
Hua-Shan
HS
Liu
Center for Biomedical Image Computing and Analytics, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. christos.davatzikos@uphs.upenn.edu.
Christos
C
Davatzikos
Center for Biomedical Image Computing and Analytics, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. guray.erus@uphs.upenn.edu.
Guray
G
Erus
Center for Biomedical Image Computing and Analytics, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. jimit.doshi@uphs.upenn.edu.
Jimit J
JJ
Doshi
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. schultzrt@email.chop.edu.|Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. schultzrt@email.chop.edu.|Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. schultzrt@email.chop.edu.
Robert T
RT
Schultz
Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA. herringtonj@email.chop.edu.|Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. herringtonj@email.chop.edu.
John D
JD
Herrington
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. jawad@email.chop.edu.|Children's Hospital of Philadelphia, Philadelphia, PA, USA. jawad@email.chop.edu.
Abbas F
AF
Jawad
Division of Pediatric Nephrology, Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA. divya.moodalbail@nemours.org.
Divya G
DG
Moodalbail
Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. gur@upenn.edu.|Brain and Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. gur@upenn.edu.
Ruben C
RC
Gur
Brain and Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. alliport@mail.med.upenn.edu.
Allison M
AM
Port
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. radcliffe@email.chop.edu.|Division of Developmental and Behavioral Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. radcliffe@email.chop.edu.
Jerilynn
J
Radcliffe
Department of Allied Health Sciences, University of North Carolina School of Medicine, Chapel Hill, NC, USA. stephen_hooper@med.unc.edu.
Stephen R
SR
Hooper
Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, USA. furths@email.chop.edu.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. furths@email.chop.edu.|Department of Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. furths@email.chop.edu.
Susan L
SL
Furth
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000150:complications / Q000473:pathology / Q000523:psychology*; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology / Q000523:psychology*; D002648:Child; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology / Q000523:psychology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology / Q000523:psychology*; D055815:Young Adult