Abstract
In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer’s disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18–85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.
| Original language | English (US) |
|---|---|
| Article number | e46179 |
| Journal | eLife |
| Volume | 8 |
| DOIs | |
| State | Published - Jun 2019 |
ASJC Scopus subject areas
- Neuroscience(all)
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)
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Family history of alzheimer’s disease alters cognition and is modified by medical and genetic factors. / Talboom, Joshua S.; Håberg, Asta; De Both, Matthew D.; Naymik, Marcus A.; Schrauwen, Isabelle; Lewis, Candace R.; Bertinelli, Stacy F.; Hammersland, Callie; Fritz, Mason A.; Myers, Amanda J.; Hay, Meredith; Barnes, Carol A.; Glisky, Elizabeth; Ryan, Lee; Huentelman, Matthew J.
In: eLife, Vol. 8, e46179, 06.2019.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Family history of alzheimer’s disease alters cognition and is modified by medical and genetic factors
AU - Talboom, Joshua S.
AU - Håberg, Asta
AU - De Both, Matthew D.
AU - Naymik, Marcus A.
AU - Schrauwen, Isabelle
AU - Lewis, Candace R.
AU - Bertinelli, Stacy F.
AU - Hammersland, Callie
AU - Fritz, Mason A.
AU - Myers, Amanda J.
AU - Hay, Meredith
AU - Barnes, Carol A.
AU - Glisky, Elizabeth
AU - Ryan, Lee
AU - Huentelman, Matthew J.
N1 - Funding Information: The authors wish to acknowledge the Mueller Family Charitable Trust for funding the initial creation of the MindCrowd site and to Mike Mueller for his significant donation of personal time during the development, testing, and ongoing evolution of the study. This work was also supported in part by the State of Arizona DHS in support of the Arizona Alzheimer’s Consortium (PI; Eric Reiman), the Flinn Foundation (PI; Matt Huentelman), The McKnight Brain Research Foundation, The Fulbright Program, and NIH-NIA grants R01-AG041232 (Multiple-PI; to Matt Huentelman and Amanda Myers) and R01-AG049465-05 (PI; Carol Barnes). We also acknowledge the following individual donors: Kris-tina Adams, Beverly Aldous, Peter Ax, Betty Barnes, Catherine Bartlett, Murali and Jori Bathina, Cathleen Becskehazy, Matt and Mary Birk, David Blake, Irwin and Marie Bliss, Sandra Bolduc, Michael and Anna Brennan, William and Tess Burleson, Christopher and Jan Cacheris, Thomas Clancy, Margaret Clark, Larry and Carol Clemmensen, Ronald Cocciole, James Conley, Linda Bowles Da Silva, Vernon Daniel, Birdeena Dapples, Virginia Davis, Brent Donaldson, Bennett and Jacquie Dorrance, Robert and Annette Dunlap, Julia Eggleston, Pat Eisenberg, Rhian Ellis, Mark Flint, Jayne Gasperson, Don and Kim Gray, Jane Hamblin, Elaine Harris, Steve and Suzi Hilton, Carolyn Horton, Jeffrey Hunt, Intel Foundation, Bill Johnsen, Marie Johnson, A.J. Kearney, Jeri Kelley, Maria Cesaria Lancaster, Bill and Julie Lavidge, Debra Lesperance, Donald Lindsay, Nate Lowrie, Marsha Luey, Terry and Gabriela McManus, Burt Moorhouse, Kathleen Parker, Brian Patrick, Nils Pearson, Lawrence Reba, Sharii Rey, Mary Riter, Lucy Roth, Victoria Ruppert, Roger Salomon, Patty Sandler, Seymour Sargent, Michael and Sheryl Sculley, Donald J Stanforth, Dean Taylor, Thomas Thimons, Paul Timm, Rex Travis, Karl Volk, Patricia Wargo, Philip Welp, Michael Wintory, Stanley Wolf, and thirty-two additional anonymous donors. Fundraising efforts for MindCrowd were led by the TGen Foundation staff, and we would like to acknowledge the efforts of Michael Bassoff and T.J. Isaacs. Design, testing, and administrative support The MindCrowd site was built by The Lavidge Company (Scottsdale, Arizona) and we acknowledge their support through the donation of significant pro bono employee hours and resources, in particular, those provided by Stephen Heitz, Meghan Mast, and Bill Lavidge. John Tabar provided project management and volunteer hour contributions during the design and testing phases of MindCrowd. Members or past members of the Huentelman laboratory are also recognized for their conceptual contributions to MindCrowd including Chris Balak, Ashley Siniard, Adrienne Henderson-Smith, Ryan Richholt, Mari Turk, Ryan Bruhns, Claire Cambron, Amanda Wolfe, and Jim Peden. We also acknowledge the administrative support of Stephanie Althoff, Kara Karaniuk, Mary Ellen Ahearn, and Stephanie Buchholtz (for CRC and IRB activities); Galen Perry, Jeffrey Watkins and Steve Yoz-wiak (for marketing and communications activities); and Valerie Jones, Brian Anderson, Kati Koktavy, and Russ Brandt (for administrative coordination and project management). William Burleson, James Lowey, and Planet Argon (Gary Blessington and Robby Russell) have contributed to the current version and administration of the MindCrowd website. We acknowledge LeaseHawk (Scottsdale, Arizona) for participating in the alpha testing of MindCrowd and for providing quiet ‘bunker’ facilities during the drafting of this manuscript. Recruitment and social media Heather Hanson, Anna Gunderson, Bryeson Rodgers, Emily Schilling, Tayllor Lillestol, and Emma Totten (and her company BuzzlyMedia) participated in social media campaigns for MindCrowd. Jen-nifer Jenkin and Julie Euber perform public outreach duties for MindCrowd. The Alzheimer’s Association TrialMatch service for directing participants to MindCrowd and we acknowledge the support of the Alzheimer’s Association Desert Southwest Chapter (Phoenix, Arizona) and the past Executive Director Deborah Schaus and current Executive Director Dan Lawler in facilitating those efforts. The Alzheimer’s Prevention Initiative at Banner Alzheimer’s Institute (Phoenix, Arizona) also helped with recruitment, and we acknowledge their support as well, including the Program Director Jessica Langbaum. Lastly, we would like to thank our MindCrowd Facebook friends, Twitter followers, Red-ditors, and other social media participants especially Lynda Carter, Ashton Kutcher, and Valerie Ber-tinelli for their support in the social marketing of MindCrowd. In memoriam This manuscript is dedicated to the memory of our dear friend and colleague Jason Corneveaux, who originated the MindCrowd name. His contributions to our laboratory were innumerable and significant, and he continues to be sorely missed by our research team. Funding Information: This paper was supported by the following grants: Mueller Family Charitable Trust to Matthew J Huentelman. Arizona Department of Health Services Arizona DHS in support of the Arizona Alzheimer's Consortium to Matthew J Huentelman. Flinn Foundation to Matthew J Huentelman. National Institutes of Health R01-AG041232 to Amanda J Myers. National Institutes of Health R01-AG049465-05 to Carol A Barnes. Publisher Copyright: © Talboom et al.
PY - 2019/6
Y1 - 2019/6
N2 - In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer’s disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18–85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.
AB - In humans, a first-degree family history of dementia (FH) is a well-documented risk factor for Alzheimer’s disease (AD); however, the influence of FH on cognition across the lifespan is poorly understood. To address this issue, we developed an internet-based paired-associates learning (PAL) task and tested 59,571 participants between the ages of 18–85. FH was associated with lower PAL performance in both sexes under 65 years old. Modifiers of this effect of FH on PAL performance included age, sex, education, and diabetes. The Apolipoprotein E ε4 allele was also associated with lower PAL scores in FH positive individuals. Here we show, FH is associated with reduced PAL performance four decades before the typical onset of AD; additionally, several heritable and non-heritable modifiers of this effect were identified.
UR - http://www.scopus.com/inward/record.url?scp=85069297486&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069297486&partnerID=8YFLogxK
U2 - 10.7554/eLife.46179.001
DO - 10.7554/eLife.46179.001
M3 - Article
C2 - 31210642
AN - SCOPUS:85069297486
VL - 8
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e46179
ER -