Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease

Nelly Joseph-Mathurin; Yi Su; Tyler M Blazey; Mateusz Jasielec; Andrei Vlassenko; Karl Friedrichsen; Brian A Gordon; Russ C Hornbeck; Lisa Cash; Beau M Ances; Thomas Veale; David M Cash; Adam M Brickman; Virginia Buckles; Nigel J Cairns; Carlos Cruchaga; Alison Goate; Clifford R Jack Jr; Celeste Karch; William Klunk; Robert A Koeppe; Daniel S Marcus; Richard Mayeux; Eric McDade; James M Noble; John Ringman; Andrew J Saykin; Paul M Thompson; Chengjie Xiong; John C Morris; Randall J Bateman; Tammie L S Benzinger; Dominantly Inherited Alzheimer Network

doi:10.1016/j.dadm.2018.08.012

Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease

Alzheimers Dement (Amst). 2018 Sep 27:10:669-677. doi: 10.1016/j.dadm.2018.08.012. eCollection 2018.

Authors

Nelly Joseph-Mathurin¹, Yi Su², Tyler M Blazey¹, Mateusz Jasielec³, Andrei Vlassenko¹, Karl Friedrichsen¹, Brian A Gordon¹, Russ C Hornbeck¹, Lisa Cash¹, Beau M Ances⁴, Thomas Veale⁵, David M Cash⁵, Adam M Brickman⁶, Virginia Buckles⁴, Nigel J Cairns⁴, Carlos Cruchaga⁷, Alison Goate⁸, Clifford R Jack Jr⁹, Celeste Karch⁴, William Klunk¹⁰, Robert A Koeppe¹¹, Daniel S Marcus¹, Richard Mayeux⁶, Eric McDade⁴, James M Noble⁶, John Ringman¹², Andrew J Saykin¹³, Paul M Thompson¹⁴, Chengjie Xiong³, John C Morris⁴, Randall J Bateman⁴, Tammie L S Benzinger¹; Dominantly Inherited Alzheimer Network

Affiliations

¹ Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.
² Banner Alzheimer's Institute, Phoenix, AZ, USA.
³ Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA.
⁴ Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
⁵ Dementia Research Centre, UCL Institute of Neurology, London, UK.
⁶ Department of Neurology, Columbia University Medical Center, New York, NY, USA.
⁷ Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
⁸ Neuroscience Department Laboratories, Mount Sinai School of Medicine, New York, NY, USA.
⁹ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
¹⁰ Departments of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹¹ Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
¹² Memory and Aging Center, Department of Neurology, Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
¹³ Center for Neuroimaging, Department of Radiology and Imaging Science, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁴ Laboratory of Neuroimaging, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Abstract

Introduction: ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using ¹¹C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET.

Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history.

Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity.

Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure.

Keywords: Alzheimer's disease; FDG; Neuronal injury; Perfusion; PiB.

Abstract

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