Richard J Caselli1, Dona E C Locke2, Amylou C Dueck3, David S Knopman4, Bryan K Woodruff5, Charlene Hoffman-Snyder5, Rosa Rademakers6, Adam S Fleisher7, Eric M Reiman7. 1. Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA. Electronic address: caselli.richard@mayo.edu. 2. Division of Psychology, Mayo Clinic Arizona, Scottsdale, AZ, USA. 3. Department of Biostatistics, Mayo Clinic Arizona, Scottsdale, AZ, USA. 4. Department of Neurology, Mayo Clinic Rochester, MN, USA. 5. Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA. 6. Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA. 7. Banner Alzheimer's Institute, Phoenix, AZ, USA.
Abstract
OBJECTIVE: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. METHODS: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. RESULTS: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. CONCLUSIONS: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.
OBJECTIVE: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. METHODS: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. RESULTS: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. CONCLUSIONS: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.
Authors: Sarah E MacPherson; Mario A Parra; Sonia Moreno; Francisco Lopera; Sergio Della Sala Journal: J Int Neuropsychol Soc Date: 2011-12-02 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: William E Klunk; Julie C Price; Chester A Mathis; Nicholas D Tsopelas; Brian J Lopresti; Scott K Ziolko; Wenzhu Bi; Jessica A Hoge; Ann D Cohen; Milos D Ikonomovic; Judith A Saxton; Beth E Snitz; Daniel A Pollen; Majaz Moonis; Carol F Lippa; Joan M Swearer; Keith A Johnson; Dorene M Rentz; Alan J Fischman; Howard J Aizenstein; Steven T DeKosky Journal: J Neurosci Date: 2007-06-06 Impact factor: 6.167
Authors: Hélène Amieva; Mélanie Le Goff; Xavier Millet; Jean Marc Orgogozo; Karine Pérès; Pascale Barberger-Gateau; Hélène Jacqmin-Gadda; Jean François Dartigues Journal: Ann Neurol Date: 2008-11 Impact factor: 10.422
Authors: Randall J Bateman; Paul S Aisen; Bart De Strooper; Nick C Fox; Cynthia A Lemere; John M Ringman; Stephen Salloway; Reisa A Sperling; Manfred Windisch; Chengjie Xiong Journal: Alzheimers Res Ther Date: 2011-01-06 Impact factor: 6.982
Authors: Richard J Caselli; Blake T Langlais; Amylou C Dueck; Dona E C Locke; Bryan K Woodruff Journal: Alzheimer Dis Assoc Disord Date: 2018 Oct-Dec Impact factor: 2.703
Authors: Kaitlin B Casaletto; Michael E Ward; Nicholas S Baker; Brianne M Bettcher; Jeffrey M Gelfand; Yaqiao Li; Robert Chen; Shubir Dutt; Bruce Miller; Joel H Kramer; Ari J Green Journal: Neurobiol Aging Date: 2016-12-21 Impact factor: 4.673
Authors: Leslie S Gaynor; Rosie E Curiel Cid; Ailyn Penate; Mónica Rosselli; Sara N Burke; Meredith Wicklund; David A Loewenstein; Russell M Bauer Journal: J Int Neuropsychol Soc Date: 2019-08 Impact factor: 2.892
Authors: Cynthia M Stonnington; Brian Harel; Dona E C Locke; Joseph G Hentz; Nan Zhang; Paul Maruff; Richard J Caselli Journal: Alzheimer Dis Assoc Disord Date: 2017 Oct-Dec Impact factor: 2.703
Authors: Lindsay R Clark; Rebecca L Koscik; Christopher R Nicholas; Ozioma C Okonkwo; Corinne D Engelman; Lisa C Bratzke; Kirk J Hogan; Kimberly D Mueller; Barbara B Bendlin; Cynthia M Carlsson; Sanjay Asthana; Mark A Sager; Bruce P Hermann; Sterling C Johnson Journal: Arch Clin Neuropsychol Date: 2016-11-22 Impact factor: 2.813
Authors: D D Correa; M Kryza-Lacombe; X Zhou; R E Baser; B J Beattie; Z Beiene; J Humm; L M DeAngelis; I Orlow; W Weber; J Osborne Journal: J Neurooncol Date: 2017-11-22 Impact factor: 4.130