Divergent Longitudinal Propagation of White Matter Degradation in Logopenic and Semantic Variants of Primary Progressive Aphasia.
BACKGROUND
Clinico-pathological distinction of primary progressive aphasia (PPA) can be challenging at clinic presentation. In particular, cross-sectional neuroimaging signatures across the logopenic (lvPPA) and semantic (svPPA) variants are difficult to establish, with longitudinal profiles showing greater divergence.


OBJECTIVE
Assess longitudinal propagation of white matter degradation in lvPPA and svPPA to determine disease progression over time, and whether this reflects distinct underlying pathology.


METHODS
A cohort of 27 patients with dementia (12 lvPPA; 15 svPPA) and 12 healthy controls were assessed at baseline and 1-year follow-up on the Addenbrooke's Cognitive Examination-Revised and Sydney Language Battery. Diffusion weighted images were collected at both time-points and analyzed for longitudinal white matter change using DTI-TK and TBSS.


RESULTS
LvPPA patients showed a significant decline in naming and repetition, over 1 year, while svPPA patients declined in naming and comprehension. Longitudinal imaging revealed widespread bilateral degradation of white matter tracts in lvPPA over a 1-year period with early involvement of the left posterior inferior longitudinal fasciculus (ILF). SvPPA demonstrated focal left lateralized white matter degradation involving the uncinate fasciculus (UF) and anterior ILF, propagating to the right UF with disease progression.


CONCLUSIONS
LvPPA and svPPA cohorts showed distinct longitudinal cognitive and white matter profiles. We propose differences in multi-centric and focal white matter dysfunction in lvPPA and svPPA, respectively, reflect underlying pathological differences. The clinical relevance of white matter degradation and mechanisms underlying disease propagation are discussed.
Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
Sicong
S
Tu
Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|Faculty of Health Sciences, University of Sydney, Sydney, Australia.
Cristian E
CE
Leyton
Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
John R
JR
Hodges
Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.
Olivier
O
Piguet
Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia.|School of Medical Sciences, University of New South Wales, Sydney, Australia.|Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Michael
M
Hornberger
D000368:Aged; D000704:Analysis of Variance; D018888:Aphasia, Primary Progressive / Q000145:classification / Q000150:complications*; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009275:Names; D009483:Neuropsychological Tests; D012660:Semantics
Diffusion tensor imaging; frontotemporal dementia; primary progressive aphasia; white matter