Progression of Microstructural Degeneration in Progressive Supranuclear Palsy and Corticobasal Syndrome: A Longitudinal Diffusion Tensor Imaging Study.
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.
Center for Imaging of Neurodegenerative Diseases, VA Medical Center San Francisco, San Francisco, CA, United States of America.|Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States of America.
Yu
Y
Zhang
Center for Imaging of Neurodegenerative Diseases, VA Medical Center San Francisco, San Francisco, CA, United States of America.|Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States of America.
Rudolph
R
Walter
Center for Imaging of Neurodegenerative Diseases, VA Medical Center San Francisco, San Francisco, CA, United States of America.|Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States of America.
Peter
P
Ng
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Phi N
PN
Luong
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Shubir
S
Dutt
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Hilary
H
Heuer
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Julio C
JC
Rojas-Rodriguez
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Richard
R
Tsai
Department of Neurosciences, Movement Disorder Center, University of California San Diego, San Diego, CA, United States of America.
Irene
I
Litvan
Department of Neurology, Massachusetts General Hospital, Boston, MA, United States of America.
Bradford C
BC
Dickerson
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.|University Health Network and Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.
Maria Carmela
MC
Tartaglia
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Gil
G
Rabinovici
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Bruce L
BL
Miller
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Howard J
HJ
Rosen
Center for Imaging of Neurodegenerative Diseases, VA Medical Center San Francisco, San Francisco, CA, United States of America.|Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States of America.
Norbert
N
Schuff
Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, United States of America.
Adam L
AL
Boxer
D000368:Aged; D016880:Anisotropy; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D065837:Middle Cerebellar Peduncle / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D013577:Syndrome; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology