Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study.
BACKGROUND
Different clinical syndromes can arise from Alzheimer's disease (AD) neuropathology, including dementia of the Alzheimer's type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA).


OBJECTIVE
To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD.


METHODS
Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups.


RESULTS
All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum.


CONCLUSIONS
These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Ajay
A
Madhavan
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Christopher G
CG
Schwarz
Department of Neurology (Speech Pathology), Mayo Clinic, Rochester, MN, USA.
Joseph R
JR
Duffy
Department of Neurology (Speech Pathology), Mayo Clinic, Rochester, MN, USA.
Edythe A
EA
Strand
Department of Psychiatry and Psychology (Neuropsychology), Mayo Clinic, Rochester, MN, USA.
Mary M
MM
Machulda
Department of Neurology (Behavioral Neurology), Mayo Clinic, Rochester, MN, USA.
Daniel A
DA
Drubach
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Kejal
K
Kantarci
Department of Health Sciences Research (Biostatistics), Mayo Clinic, Rochester, MN, USA.
Scott A
SA
Przybelski
Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
Robert I
RI
Reid
Department of Radiology, Mayo Clinic, Rochester, MN, USA.|Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
Matthew L
ML
Senjem
Department of Radiology, Mayo Clinic, Rochester, MN, USA.|Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
Jeffrey L
JL
Gunter
Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
Liana G
LG
Apostolova
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Val J
VJ
Lowe
Department of Neurology (Behavioral Neurology), Mayo Clinic, Rochester, MN, USA.
Ronald C
RC
Petersen
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Clifford R
CR
Jack
Department of Neurology (Behavioral Neurology), Mayo Clinic, Rochester, MN, USA.
Keith A
KA
Josephs
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Jennifer L
JL
Whitwell
D000368:Aged; D000544:Alzheimer Disease / Q000145:classification / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D000814:Aniline Compounds / Q000493:pharmacokinetics; D016880:Anisotropy; D018888:Aphasia, Primary Progressive / Q000000981:diagnostic imaging / Q000473:pathology; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D013844:Thiazoles / Q000493:pharmacokinetics; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles
Alzheimer’s disease; diffusion tensor imaging; logopenic; posterior cortical atrophy; white matter