TY - JOUR
T1 - Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease
AU - Sintini, Irene
AU - Martin, Peter R.
AU - Graff-Radford, Jonathan
AU - Senjem, Matthew L.
AU - Schwarz, Christopher G.
AU - Machulda, Mary M.
AU - Spychalla, Anthony J.
AU - Drubach, Daniel A.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Lowe, Val J.
AU - Jack, Clifford R.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (grant numbers: R01-AG50603 , R21-NS94684 and U01-AG006786 ). The sponsors played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. We would like to greatly thank AVID Radiopharmaceuticals, Inc., for their support in supplying the AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.
Publisher Copyright:
© 2019 The Authors
PY - 2019
Y1 - 2019
N2 - The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.
AB - The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [ 18 F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.
KW - Atrophy
KW - Atypical AD
KW - Longitudinal tau-PET
KW - Multimodal imaging
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U2 - 10.1016/j.nicl.2019.101823
DO - 10.1016/j.nicl.2019.101823
M3 - Article
C2 - 31004914
AN - SCOPUS:85064253404
SN - 2213-1582
VL - 23
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 101823
ER -