title: Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity.
abstract: BACKGROUND
  Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition.
  
  
  METHODS
  Magnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test.
  
  
  RESULTS
  Caudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores-higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates.
  
  
  CONCLUSIONS
  Behavioural symptoms and severity of bvFTD are correlated with abnormalities in striatal size and shape. This adds to the promise of imaging the striatum as a biomarker in this disease.
authors.affiliation: Illawarra Shoalhaven Local Health District, Wollongong, Australia; Graduate School of Medicine, University of Wollongong, Wollongong, Australia.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Macfarlane
authors.affiliation: Graduate School of Medicine, University of Wollongong, Wollongong, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Jakabek
authors.affiliation: Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Walterfang
authors.affiliation: Department of Psychology, Lund University, Lund, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Vestberg
authors.affiliation: Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.affiliation: Research Centre for the Neurosciences of Ageing, Academic Unit of Psychiatry and Addiction Medicine, School of Clinical Medicine, Australian National University Medical School, Canberra, Australia.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Wilkes
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Center for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden; Diagnostic Radiology, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Research Centre for the Neurosciences of Ageing, Academic Unit of Psychiatry and Addiction Medicine, School of Clinical Medicine, Australian National University Medical School, Canberra, Australia.
authors.forename: Jeffrey C L
authors.initials: JC
authors.lastname: Looi
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden; Geriatric Psychiatry Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Alexander Frizell
authors.initials: AF
authors.lastname: Santillo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001526:Behavioral Symptoms; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index