title: Frontal white matter injuries predestine gait difficulties in Parkinson's disease.
abstract: OBJECTIVE
  This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease.
  
  
  METHODS
  One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold.
  
  
  RESULTS
  PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05).
  
  
  CONCLUSIONS
  Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Lenfeldt
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Holmlund
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Birgander
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Forsgren
mesh_terms: D000359:Aftercare; D000368:Aged; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging*; D020233:Gait Disorders, Neurologic / Q000000981:diagnostic imaging* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging*; D014202:Tremor / Q000000981:diagnostic imaging* / Q000209:etiology; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: anisotropy; diffusion tensor imaging; gait; parkinsonism; tremor