title: The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis.
abstract: OBJECTIVE
  Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS.
  
  
  METHODS
  In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI.
  
  
  RESULTS
  Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 μl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS.
  
  
  CONCLUSIONS
  Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.|Department of Neuroinflammation, Queen Square MS Centre, NMR Research Unit, UCL Institute of Neurology, London, UK.
authors.forename: Ö
authors.initials: Ö
authors.lastname: Yaldizli
authors.affiliation: Department of Cognitive Psychology and Methodology, University of Basel, Basel, Switzerland.
authors.forename: I-K
authors.initials: IK
authors.lastname: Penner
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yonekawa
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Naegelin
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kuhle
authors.affiliation: Department of Neuroinflammation, Queen Square MS Centre, NMR Research Unit, UCL Institute of Neurology, London, UK.|Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pardini
authors.affiliation: Department of Neuroinflammation, Queen Square MS Centre, NMR Research Unit, UCL Institute of Neurology, London, UK.|National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Chard
authors.affiliation: Department of Radiology, Division of Neuroradiology, University Hospital Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Stippich
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: J-I
authors.initials: JI
authors.lastname: Kira
authors.affiliation: Medical Image Analysis Center, Basel, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Bendfeldt
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.|Department of Radiology, Division of Neuroradiology, University Hospital Basel, Basel, Switzerland.|Medical Image Analysis Center, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Amann
authors.affiliation: Medical Image Analysis Center, Basel, Switzerland.
authors.forename: E-W
authors.initials: EW
authors.lastname: Radue
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.|Department of Neurology, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Sprenger
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D003863:Depression / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D009830:Olfactory Bulb / Q000473:pathology*
keywords: cognitive impairment; depression; fatigue; magnetic resonance imaging; multiple sclerosis; olfactory bulb volume