Cynthia M Stonnington1, Kewei Chen2, Wendy Lee2, Dona E C Locke3, Amylou C Dueck4, Xiaofen Liu2, Auttawut Roontiva2, Adam S Fleisher5, Richard J Caselli6, Eric M Reiman2. 1. Department of Psychiatry & Psychology, Mayo Clinic in Arizona, Scottsdale, AZ, USA. Electronic address: stonnington.cynthia@mayo.edu. 2. Banner Alzheimer's Institute, Phoenix, AZ, USA. 3. Department of Psychiatry & Psychology, Mayo Clinic in Arizona, Scottsdale, AZ, USA. 4. Department of Biostatistics, Mayo Clinic in Arizona, Scottsdale, AZ, USA. 5. Banner Alzheimer's Institute, Phoenix, AZ, USA; Department of Neurosciences, University of California-San Diego, San Diego, CA, USA. 6. Department of Neurology, Mayo Clinic in Arizona, Scottsdale, AZ, USA.
Abstract
BACKGROUND: It is not known whether preclinical cognitive decline is associated with fibrillar β-amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status. METHODS: From a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden. RESULTS: At P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. CONCLUSIONS: Asymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.
BACKGROUND: It is not known whether preclinical cognitive decline is associated with fibrillar β-amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status. METHODS: From a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden. RESULTS: At P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. CONCLUSIONS: Asymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.
Authors: Otto Pedraza; Glenn E Smith; Robert J Ivnik; Floyd B Willis; Tanis J Ferman; Ronald C Petersen; Neill R Graff-Radford; John A Lucas Journal: J Int Neuropsychol Soc Date: 2007-05-18 Impact factor: 2.892
Authors: Richard J Caselli; Amylou C Dueck; David Osborne; Marwan N Sabbagh; Donald J Connor; Geoffrey L Ahern; Leslie C Baxter; Steven Z Rapcsak; Jiong Shi; Bryan K Woodruff; Dona E C Locke; Charlene Hoffman Snyder; Gene E Alexander; Rosa Rademakers; Eric M Reiman Journal: N Engl J Med Date: 2009-07-16 Impact factor: 91.245
Authors: Yen Ying Lim; Kathryn A Ellis; Robert H Pietrzak; David Ames; David Darby; Karra Harrington; Ralph N Martins; Colin L Masters; Christopher Rowe; Greg Savage; Cassandra Szoeke; Victor L Villemagne; Paul Maruff Journal: Neurology Date: 2012-10-16 Impact factor: 9.910
Authors: Eric M Reiman; Kewei Chen; Xiaofen Liu; Daniel Bandy; Meixiang Yu; Wendy Lee; Napatkamon Ayutyanont; Jennifer Keppler; Stephanie A Reeder; Jessica B S Langbaum; Gene E Alexander; William E Klunk; Chester A Mathis; Julie C Price; Howard J Aizenstein; Steven T DeKosky; Richard J Caselli Journal: Proc Natl Acad Sci U S A Date: 2009-04-03 Impact factor: 11.205
Authors: R J Caselli; E M Reiman; D Osborne; J G Hentz; L C Baxter; J L Hernandez; G G Alexander Journal: Neurology Date: 2004-06-08 Impact factor: 9.910
Authors: Richard J Caselli; Eric M Reiman; Dona E C Locke; Michael L Hutton; Joseph G Hentz; Charlene Hoffman-Snyder; Bryan K Woodruff; Gene E Alexander; David Osborne Journal: Arch Neurol Date: 2007-09
Authors: Murat Bilgel; Rebecca L Koscik; Yang An; Jerry L Prince; Susan M Resnick; Sterling C Johnson; Bruno M Jedynak Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Jessica B Langbaum; Suzanne B Hendrix; Napatkamon Ayutyanont; Kewei Chen; Adam S Fleisher; Raj C Shah; Lisa L Barnes; David A Bennett; Pierre N Tariot; Eric M Reiman Journal: Alzheimers Dement Date: 2014-04-21 Impact factor: 21.566
Authors: Li-Ming Wang; Qi Wu; Ryan A Kirk; Kevin P Horn; Ahmed H Ebada Salem; John M Hoffman; Jeffrey T Yap; Joshua A Sonnen; Rheal A Towner; Fernando A Bozza; Rosana S Rodrigues; Kathryn A Morton Journal: Am J Nucl Med Mol Imaging Date: 2018-04-25
Authors: Napatkamon Ayutyanont; Jessica B S Langbaum; Suzanne B Hendrix; Kewei Chen; Adam S Fleisher; Michel Friesenhahn; Michael Ward; Camilo Aguirre; Natalia Acosta-Baena; Lucìa Madrigal; Claudia Muñoz; Victoria Tirado; Sonia Moreno; Pierre N Tariot; Francisco Lopera; Eric M Reiman Journal: J Clin Psychiatry Date: 2014-06 Impact factor: 4.384
Authors: Michał Wiciński; Bartosz Malinowski; Oskar Puk; Karol Górski; Dawid Adamkiewicz; Grzegorz Chojnacki; Maciej Walczak; Eryk Wódkiewicz; Monika Szambelan; Paulina Adamska; Kamila Skibińska; Maciej Socha; Maciej Słupski; Katarzyna Pawlak-Osińska Journal: Biomed Res Int Date: 2019-10-17 Impact factor: 3.411
Authors: Felix Carbonell; Arnaud Charil; Alex P Zijdenbos; Alan C Evans; Barry J Bedell Journal: J Cereb Blood Flow Metab Date: 2014-04-16 Impact factor: 6.200
Authors: Y Y Lim; V L Villemagne; S M Laws; R H Pietrzak; P J Snyder; D Ames; K A Ellis; K Harrington; A Rembach; R N Martins; C C Rowe; C L Masters; P Maruff Journal: Mol Psychiatry Date: 2014-10-07 Impact factor: 15.992