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Progression of Microstructural Degeneration in Progressive Supranuclear Palsy and Corticobasal Syndrome: A Longitudinal Diffusion Tensor Imaging Study.

  • Author(s): Zhang, Yu
  • Walter, Rudolph
  • Ng, Peter
  • Luong, Phi N
  • Dutt, Shubir
  • Heuer, Hilary
  • Rojas-Rodriguez, Julio C
  • Tsai, Richard
  • Litvan, Irene
  • Dickerson, Bradford C
  • Tartaglia, Maria Carmela
  • Rabinovici, Gil
  • Miller, Bruce L
  • Rosen, Howard J
  • Schuff, Norbert
  • Boxer, Adam L
  • et al.
Abstract

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are both 4 microtubule binding repeat tauopathy related disorders. Clinical trials need new biomarkers to assess the effectiveness of tau-directed therapies. This study investigated the regional distribution of longitudinal diffusion tensor imaging changes, measured by fractional anisotropy, radial and axial diffusivity over 6 months median interval, in 23 normal control subjects, 35 patients with PSP, and 25 patients with CBS. A mixed-effects framework was used to test longitudinal changes within and between groups. Correlations between changes in diffusion variables and clinical progression were also tested. The study found that over a 6 month period and compared to controls, the most prominent changes in PSP were up to 3±1% higher rates of FA reduction predominantly in superior cerebellar peduncles, and up to 18±6% higher rates of diffusivity increases in caudate nuclei. The most prominent changes in CBS compared to controls were up to 4±1% higher rates of anisotropy reduction and 18±6% higher rates of diffusivity increase in basal ganglia and widespread white matter regions. Compared to PSP, CBS was mainly associated with up to 3±1% greater rates of anisotropy reduction around the central sulci, and 11±3% greater rates of diffusivity increase in superior fronto-occipital fascicules. Rates of diffusivity increases in the superior cerebellar peduncle correlated with rates of ocular motor decline in PSP patients. This study demonstrated that longitudinal diffusion tensor imaging measurement is a promising surrogate marker of disease progression in PSP and CBS over a relatively short period.

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