Andrew J Aschenbrenner1, Bryan D James2, Eric McDade1, Guoqiao Wang3, Yen Ying Lim4, Tammie L S Benzinger1,5, Carlos Cruchaga1,6, Alison Goate7, Chengjie Xiong1,3, Richard Perrin8, Virginia Buckles1, Ricardo Allegri9, Sarah B Berman10, Jasmeer P Chhatwal11, Anne Fagan1, Martin Farlow12, Antoinette O'Connor13, Bernardino Ghetti14, Neill Graff-Radford15, Jill Goldman16, Susanne Gräber17, Celeste M Karch1,6, Jae-Hong Lee18, Johannes Levin19,20, Ralph N Martins21,22, Colin Masters4, Hiroshi Mori23, James Noble16, Stephen Salloway24, Peter Schofield25,26, John C Morris1, Randall J Bateman1, Jason Hassenstab1. 1. Charles F. and Joanne Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. 2. Rush Alzheimer's Disease Center, Rush University Medical Center, Department of Internal Medicine, Chicago, IL, USA. 3. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA. 4. The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia. 5. Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. 6. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. 7. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 8. Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA. 9. FLENI, Buenos Aires, Argentina. 10. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. 11. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 12. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA. 13. Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK. 14. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. 15. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. 16. Department of Neurology, Columbia University, New York, NY, USA. 17. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. 18. Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. 19. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 20. Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany. 21. Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia. 22. Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia. 23. Osaka City University Medical School, Asahi Machi Abenoku, Osaka, Japan. 24. Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA. 25. Neuroscience Research Australia, Sydney, NSW, Australia. 26. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Abstract
INTRODUCTION: Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. METHODS: Mutation carriers and non-carriers from the Dominantly Inherited Alzheimer Network (DIAN) were stratified based on knowledge of mutation status. Rates of change on standard clinical, cognitive, and neuroimaging outcomes were examined. RESULTS: Mutation knowledge had no associations with cognitive decline, clinical progression, amyloid deposition, hippocampal volume, or depression in either carriers or non-carriers. Carriers who learned their status mid-study had slightly higher levels of depression and lower cognitive scores. DISCUSSION: Knowledge of mutation status does not affect rates of change on any measured outcome. Learning of status mid-study may confer short-term changes in cognitive functioning, or changes in cognition may influence the determination of mutation status.
INTRODUCTION: Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. METHODS: Mutation carriers and non-carriers from the Dominantly Inherited Alzheimer Network (DIAN) were stratified based on knowledge of mutation status. Rates of change on standard clinical, cognitive, and neuroimaging outcomes were examined. RESULTS: Mutation knowledge had no associations with cognitive decline, clinical progression, amyloid deposition, hippocampal volume, or depression in either carriers or non-carriers. Carriers who learned their status mid-study had slightly higher levels of depression and lower cognitive scores. DISCUSSION: Knowledge of mutation status does not affect rates of change on any measured outcome. Learning of status mid-study may confer short-term changes in cognitive functioning, or changes in cognition may influence the determination of mutation status.
Authors: Jeffrey M Burns; David K Johnson; Edward P Liebmann; Rebecca J Bothwell; Jill K Morris; Eric D Vidoni Journal: Alzheimers Dement Date: 2017-03-03 Impact factor: 21.566
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