Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease

Stephan Müller¹, Oliver Preische^{1

2}, Hamid R Sohrabi^{3

4}, Susanne Gräber^{2

5}, Mathias Jucker^{2

6}, Janko Dietzsch⁵, John M Ringman⁷, Ralph N Martins^{3

4}, Eric McDade⁸, Peter R Schofield^{9

10}, Bernardino Ghetti¹¹, Martin Rossor¹², Neill R Graff-Radford¹³, Johannes Levin¹⁴, Douglas Galasko¹⁵, Kimberly A Quaid¹⁶, Stephen Salloway¹⁷, Chengjie Xiong¹⁸, Tammie Benzinger¹⁹, Virginia Buckles¹⁹, Colin L Masters²⁰, Reisa Sperling²¹, Randall J Bateman¹⁹, John C Morris¹⁹, Christoph Laske^{22

23}

Affiliations

¹ Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany.
² German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
³ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, WA, 6027, Australia.
⁴ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, WA, 6009, Australia.
⁵ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany.
⁶ Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076, Tübingen, Germany.
⁷ Memory and Aging Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁸ University of Pittsburgh School of Medicine, Department of Neurology, 3471 5th Ave, Suite 811, Pittsburgh, PA, 15213, USA.
⁹ Neuroscience Research Australia, Randwick, Sydney, NSW, 2031, Australia.
¹⁰ School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
¹¹ Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, 46202, USA.
¹² Dementia Research Centre, Department of Neurodegeneration, UCL Institute of Neurology, Queen Square, London, WC1 3BG, UK.
¹³ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida and Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
¹⁴ German Center for Neurodegenerative Diseases (DZNE), München, Germany and Department of Neurology, Ludwig-Maximilians Universität Munich, Munich, Germany.
¹⁵ Shiley-Marcos Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, CA, USA.
¹⁶ Indiana University Center for Bioethics, 410 West 10th Street, Indianapolis, IN, 46202, USA.
¹⁷ Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
¹⁸ Division of Biostatistics, The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
¹⁹ Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, 63108, USA.
²⁰ Mental Health Research Institute, University of Melbourne, Level 5, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, 3010, Australia.
²¹ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²² German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany. christoph.laske@med.uni-tuebingen.de.
²³ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany. christoph.laske@med.uni-tuebingen.de.

PMID: 28450713
PMCID: PMC5430642
DOI: 10.1038/s41598-017-01327-w

Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease

Stephan Müller et al. Sci Rep. 2017.

. 2017 Apr 27;7(1):1225.

doi: 10.1038/s41598-017-01327-w.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany.
² German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
³ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Perth, WA, 6027, Australia.
⁴ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Nedlands, WA, 6009, Australia.
⁵ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany.
⁶ Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076, Tübingen, Germany.
⁷ Memory and Aging Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁸ University of Pittsburgh School of Medicine, Department of Neurology, 3471 5th Ave, Suite 811, Pittsburgh, PA, 15213, USA.
⁹ Neuroscience Research Australia, Randwick, Sydney, NSW, 2031, Australia.
¹⁰ School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
¹¹ Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, 46202, USA.
¹² Dementia Research Centre, Department of Neurodegeneration, UCL Institute of Neurology, Queen Square, London, WC1 3BG, UK.
¹³ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida and Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
¹⁴ German Center for Neurodegenerative Diseases (DZNE), München, Germany and Department of Neurology, Ludwig-Maximilians Universität Munich, Munich, Germany.
¹⁵ Shiley-Marcos Alzheimer's Disease Research Center, Department of Neurosciences, University of California, San Diego, CA, USA.
¹⁶ Indiana University Center for Bioethics, 410 West 10th Street, Indianapolis, IN, 46202, USA.
¹⁷ Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
¹⁸ Division of Biostatistics, The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
¹⁹ Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, 63108, USA.
²⁰ Mental Health Research Institute, University of Melbourne, Level 5, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, 3010, Australia.
²¹ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²² German Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany. christoph.laske@med.uni-tuebingen.de.
²³ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076, Tübingen, Germany. christoph.laske@med.uni-tuebingen.de.

PMID: 28450713
PMCID: PMC5430642
DOI: 10.1038/s41598-017-01327-w

Abstract

The relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. 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 Aβ 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.

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Conflict of interest statement

S.M., O.P., H.S., S.G., M.J., B.G., E.D., M.R., N.G., J.D., J.L., V.B., K.Q., C.X., T.B., C.M., R.S., and C.L. report no disclosures or potential conflicts of interest. 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”. 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.

Figures

**Figure 1**
Cross sectional data (LOESS regression analysis and the estimates and their 95% confidence limits were drawn) of body-mass index (BMI) in preclinical (CDR = 0) mutation carriers (MCs) and non-mutation carriers (NCs) in relation to the estimated years to onset (EYO). A significant difference in BMI between MCs and NCs is detected in the area where the estimated 95% confidence intervals for the regression lines don’t overlap (−11.2 years). The intersection points of the lower and upper confidence interval borders were calculated by a numerical approximation. This method was also used to detect the point, at which the two curves begun to diverge (−17.8 years). The use of scatter plots is not permitted with DIAN data as the data points can be very specific to an individual and may allow to identify its mutation status.

See this image and copyright information in PMC

References

1. Garcia-Ptacek S, Faxen-Irving G, Cermakova P, Eriksdotter M, Religa D. Body mass index in dementia. European journal of clinical nutrition. 2014;68:1204–1209. doi: 10.1038/ejcn.2014.199. - DOI - PubMed
1. Emmerzaal TL, Kiliaan AJ, Gustafson DR. 2003–2013: a decade of body mass index, Alzheimer’s disease, and dementia. Journal of Alzheimer’s disease: JAD. 2015;43:739–755. - PubMed
1. Chuang, Y. F. et al. Midlife adiposity predicts earlier onset of Alzheimer’s dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Molecular psychiatry, 10.1038/mp.2015.129 (2015). - PMC - PubMed
1. Buchman AS, et al. Change in body mass index and risk of incident Alzheimer disease. Neurology. 2005;65:892–897. doi: 10.1212/01.wnl.0000176061.33817.90. - DOI - PubMed
1. Stewart R, et al. A 32-year prospective study of change in body weight and incident dementia: the Honolulu-Asia Aging Study. Archives of neurology. 2005;62:55–60. doi: 10.1001/archneur.62.1.55. - DOI - PubMed

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Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease

Affiliations

Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical