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However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global A\u03b2 brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.<\/jats:p>","DOI":"10.1038\/s41598-017-01327-w","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T11:18:54Z","timestamp":1492773534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Stephan","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Preische","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8017-8682","authenticated-orcid":false,"given":"Hamid R.","family":"Sohrabi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Gr\u00e4ber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Jucker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janko","family":"Dietzsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Ringman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph N.","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"McDade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2967-9662","authenticated-orcid":false,"given":"Peter R.","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-8019","authenticated-orcid":false,"given":"Bernardino","family":"Ghetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Rossor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neill R.","family":"Graff-Radford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Galasko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly A.","family":"Quaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Salloway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengjie","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammie","family":"Benzinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Buckles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reisa","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Laske","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,27]]},"reference":[{"key":"1327_CR1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/ejcn.2014.199","volume":"68","author":"S Garcia-Ptacek","year":"2014","unstructured":"Garcia-Ptacek, S., Faxen-Irving, G., Cermakova, P., Eriksdotter, M. & Religa, D. 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RB has received personal compensation for activities with Link Medicine, J.A.I., Bristol-Myers Squibb Company, Pfizer Inc., Merck, SPRI, Elan Corporation, Eisai Inc., and Medtronic, Inc., received royalty payments from Washington University, and received research support from Astra Zeneca Pharmaceuticals and Merck & Co., Inc. R.N.M. is the founder and owns stock in Alzhyme. HRS has received personal compensation for activities with Pfizer and Wyeth and is the Western Australian Site Neuropsych Lead for TOMMORROW Study by the Takeda Pharmaceuticals. J.M. reports disclosures: Neither Dr. Morris nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Morris has participated or is currently participating in clinical trials of anti-dementia drugs sponsored by the following companies: Janssen Immunotherapy, and Pfizer. Dr. Morris has served as a consultant for Lilly USA. He receives research support from Eli Lilly\/Avid Radiopharmaceuticals and is funded by NIH grants # P50AG005681; P01AG003991; P01AG026276 and U19AG032438\u201d. JMR reports research support from NIH, Biogen Idec, and Eli-Lilly during the conduct of this study which is outside of the submitted work. PRS has received speaking fees from Janssen Pharmaceuticals and philanthropic support for the DIAN study from the Wicking and Mason Trusts. D.G. has served as a consultant for Prothena Pharmaceuticals, Astra-Zeneca, Balance Pharmaceuticals and Stemedica, Inc., and participates in clinical trials sponsored by Eli Lilly, Inc, Toyama and Merck Pharmaceuticals. He is funded by NIH grant AGO5131. S.S. received research support from Functional Neuromodulation, Biogen, Merck, Genentech, Roche, Lilly, and Avid Radiopharmaceuticals. He received consultation fees from Biogen, Merck, Piramal, Lilly, Genentech, and Roche. He owns no stock options or royalties and he reports no conflict of interest with this work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1225"}}