%0 Journal Article %J J Alzheimers Dis %D 2016 %T Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study. %A Madhavan, Ajay %A Schwarz, Christopher G %A Duffy, Joseph R %A Strand, Edythe A %A Machulda, Mary M %A Drubach, Daniel A %A Kantarci, Kejal %A Przybelski, Scott A %A Reid, Robert I %A Senjem, Matthew L %A Gunter, Jeffrey L %A Apostolova, Liana G %A Lowe, Val J %A Petersen, Ronald C %A Jack, Clifford R %A Josephs, Keith A %A Whitwell, Jennifer L %K Aged %K Alzheimer Disease %K Aniline Compounds %K Anisotropy %K Aphasia, Primary Progressive %K Case-Control Studies %K Diffusion Tensor Imaging %K Female %K Humans %K Image Processing, Computer-Assisted %K Male %K Middle Aged %K Nerve Fibers, Myelinated %K Neurodegenerative Diseases %K Neuropsychological Tests %K Positron-Emission Tomography %K Psychiatric Status Rating Scales %K Retrospective Studies %K Thiazoles %K White Matter %X

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.

CONCLUSION: 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.

%B J Alzheimers Dis %V 49 %P 633-43 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26484918?dopt=Abstract %R 10.3233/JAD-150502 %0 Journal Article %J Ann Neurol %D 2012 %T An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. %A Jack, Clifford R %A Knopman, David S %A Weigand, Stephen D %A Wiste, Heather J %A Vemuri, Prashanthi %A Lowe, Val %A Kantarci, Kejal %A Gunter, Jeffrey L %A Senjem, Matthew L %A Ivnik, Robert J %A Roberts, Rosebud O %A Rocca, Walter A %A Boeve, Bradley F %A Petersen, Ronald C %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Aniline Compounds %K Biomarkers %K Brain %K Cognition Disorders %K Disease Progression %K Female %K Fluorodeoxyglucose F18 %K Humans %K Longitudinal Studies %K Male %K Mental Status Schedule %K National Institute on Aging (U.S.) %K Neuropsychological Tests %K Positron-Emission Tomography %K Thiazoles %K United States %X

OBJECTIVE: A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.

METHODS: We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis, and (18) fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cutpoints. A group of 450 cognitively normal (CN) subjects from a population-based sample was used to develop cognitive cutpoints and to assess population frequencies of the different preclinical AD stages using different cutpoint criteria.

RESULTS: The new criteria subdivide the preclinical phase of AD into stages 1 to 3. To classify our CN subjects, 2 additional categories were needed. Stage 0 denotes subjects with normal AD biomarkers and no evidence of subtle cognitive impairment. Suspected non-AD pathophysiology (SNAP) denotes subjects with normal amyloid PET imaging, but abnormal neurodegeneration biomarker studies. At fixed cutpoints corresponding to 90% sensitivity for diagnosing AD and the 10th percentile of CN cognitive scores, 43% of our sample was classified as stage 0, 16% stage 1, 12 % stage 2, 3% stage 3, and 23% SNAP.

INTERPRETATION: This cross-sectional evaluation of the NIA-AA criteria for preclinical AD indicates that the 1-3 staging criteria coupled with stage 0 and SNAP categories classify 97% of CN subjects from a population-based sample, leaving only 3% unclassified. Future longitudinal validation of the criteria will be important.

%B Ann Neurol %V 71 %P 765-75 %8 2012 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/22488240?dopt=Abstract %R 10.1002/ana.22628