TY - JOUR
T1 - A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease
AU - Green, Robert C.
AU - Christensen, Kurt D.
AU - Cupples, L. Adrienne
AU - Relkin, Norman R.
AU - Whitehouse, Peter J.
AU - Royal, Charmaine D.M.
AU - Obisesan, Thomas O.
AU - Cook-Deegan, Robert
AU - Linnenbringer, Erin
AU - Butson, Melissa Barber
AU - Fasaye, Grace Ann
AU - Levinson, Elana
AU - Roberts, J. Scott
AU - Bhatt, D.
AU - Biesecker, B.
AU - Blacker, D.
AU - Chen, C.
AU - Cox, E.
AU - Davis, J. G.
AU - Farrer, L.
AU - Griffith, P.
AU - Harkins, K.
AU - Hiraki, S.
AU - Johnson, M.
AU - Johnson, S.
AU - Juengst, E.
AU - Karlawish, J.
AU - Le, L.
AU - McCarty Wood, E.
AU - Obisesan, T.
AU - Post, S.
AU - Quaid, K.
AU - Ravdin, L.
AU - Roter, D.
AU - Stern, R.
AU - Sadovnick, A.
AU - Sami, S.
AU - Sankar, P.
AU - Topol, E.
AU - Uhlmann, W.
AU - Waterston, L.
AU - Wright, L.
N1 - Funding Information:
This work was supported by National Institutes of Health ( NIH ) grants HG002213 , HG006500 , HD077671 , AG013846 , HG006993 , AG042437 , HG005092 , AG027841 , RR000533 , and RR010284 . None of the authors report conflicts of interest relevant to this manuscript.
Publisher Copyright:
© 2015 The Alzheimer's Association.
PY - 2015/10
Y1 - 2015/10
N2 - Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.
AB - Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.
KW - APOE
KW - Alzheimer
KW - Genetics
KW - Genomics
KW - Personalized medicine
KW - Risk assessment
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U2 - 10.1016/j.jalz.2014.10.014
DO - 10.1016/j.jalz.2014.10.014
M3 - Article
C2 - 25499536
AN - SCOPUS:84945438957
SN - 1552-5260
VL - 11
SP - 1222
EP - 1230
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 10
ER -