title: History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress.
abstract: BACKGROUND
  Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS.
  
  
  METHODS
  Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated.
  
  
  RESULTS
  Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation.
authors.affiliation: Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. Electronic address: timothy.durazzo@ucsf.edu.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Durazzo
authors.affiliation: Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; Departments of Psychiatry, Medicine, and Neurology, University of California, San Francisco Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Diseases Research, Perelman School of Medicine, University of Pennsylvania, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korecka
authors.affiliation: Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Diseases Research, Perelman School of Medicine, University of Pennsylvania, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Diseases Research, Perelman School of Medicine, University of Pennsylvania, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology*; D012907:Smoking / Q000134:cerebrospinal fluid* / Q000473:pathology
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes
keywords: Cerebrospinal fluid; Cigarette smoking; Elder adults; Hippocampus; Isoprostanes; Oxidative stress