title: Reduced Cholinergic Basal Forebrain Integrity Links Neonatal Complications and Adult Cognitive Deficits After Premature Birth.
abstract: Prematurely born individuals have an increased risk for long-term neurocognitive impairments. In animal models, development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that cBF integrity is impaired in prematurely born individuals and mediates adult cognitive impairments associated with prematurity.
  
  
  
  We used magnetic resonance imaging-based volumetric assessments of a cytoarchitectonically defined cBF region of interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight and 106 term-born control subjects from the same birth cohort. Magnetic resonance imaging-derived cBF volumes were studied in relation to neonatal clinical complications after delivery and intelligence measures (IQ) in adulthood.
  
  
  
  In adults who were born very preterm and/or with very low birth weight, cBF volumes were significantly reduced compared with term-born adults (-4.5% [F1,202= 11.82, p = .001]). Lower cBF volume in adults who were born very preterm and/or with very low birth weight was specifically associated with both neonatal complications (rpart,92= -.35, p < .001) and adult IQ (rpart,88= .33, p = .001) even after controlling for global gray matter and white matter volume. In a path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits.
  
  
  
  We provide first-time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery.
authors.affiliation: Germater for Neurodegenerative Diseases, Rostockn Cen. Electronic address: michel.grothe@dzne.de.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
authors.affiliation: Functional Neuroimaging Group, University Hospital Bonn, Bonn.
authors.forename: Lukas
authors.initials: L
authors.lastname: Scheef
authors.affiliation: Department of Neuroradiology, Technische Universität München, Munich, Germany; Technische Universität München-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Bäuml
authors.affiliation: Department of Neuroradiology, Technische Universität München, Munich, Germany; Technische Universität München-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Chun
authors.initials: C
authors.lastname: Meng
authors.affiliation: Functional Neuroimaging Group, University Hospital Bonn, Bonn.
authors.forename: Marcel
authors.initials: M
authors.lastname: Daamen
authors.affiliation: Department of Psychology, University of Warwick, Coventry, United Kingdom.
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumann
authors.affiliation: Department of Neuroradiology, Technische Universität München, Munich, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Zimmer
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: Department of Radiology, and Department of Neonatology, University Hospital Bonn, Bonn.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartmann
authors.affiliation: Functional Neuroimaging Group, University Hospital Bonn, Bonn.
authors.forename: Henning
authors.initials: H
authors.lastname: Boecker
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Dieter
authors.initials: D
authors.lastname: Wolke
authors.affiliation: Technische Universität München-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Afra
authors.initials: A
authors.lastname: Wohlschläger
authors.affiliation: Department of Psychiatry, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
mesh_terms: D000328:Adult; D066187:Basal Forebrain / Q000000981:diagnostic imaging / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D062071:Infant, Extremely Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology; D007360:Intelligence / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male
keywords: Intelligence; Nucleus basalis of Meynert; Perinatal stress; Preterm birth; Structural MRI; Substantia innominata