Weight Loss and Alzheimer’s Disease in Down Syndrome

Article type: Research Article

Authors: Fleming, Victoria^{a; b} | Helsel, Brian C.^c | Ptomey, Lauren T.^d | Rosas, H. Diana^e | Handen, Benjamin^f | Laymon, Charles^{g; h} | Christian, Bradley T.^a | Head, Elizabethⁱ | Mapstone, Mark^j | Lai, Florence^{i; k} | Krinsky-McHale, Sharon^l | Zaman, Shahid^m | Ances, Beau M.ⁿ | Lee, Joseph H.^o | Hartley, Sigan L.^{a; b; *} | the Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS) Consortium

Affiliations: [a] Waisman Center, University of Wisconsin-Madison, Madison, WI, USA | [b] School of Human Ecology, University of Wisconsin-Madison, WI, USA | [c] Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA | [d] Departmentof Internal Medicine, University of Kansas Medical Center, KansasCity, KS, USA | [e] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA | [g] Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA | [h] Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA | [i] Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA | [j] Department of Neurology, University of California Irvine, Irvine, CA, USA | [k] Department of Pediatrics, University of California Irvine, Irvine, CA, USA | [l] Department of Psychology, New York Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA | [m] Department of Psychiatry, Clinical School, University of Cambridge, Cambridge, UK & Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, UK | [n] Department of Neurology, Washington University Saint Louis, St. Louis, MO, USA | [o] Departments of Neurology and Epidemiology, Sergievsky Center, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA

Correspondence: [*] Correspondence to: Sigan L. Hartley, PhD, 100 Women Chair in Human Ecology, Associate Professor, Human Development and Family Studies, School of Human Ecology, Waisman Center Investigator, UW-Madison, 4101 Nancy Nicholas Hall, 1300 Linden Drive, Madison, WI 53706, USA. Tel.: +1 608 265 5424; E-mail: [email protected].

Note: [#] Data used in preparation of this article were obtained from the Neurodegeneration in Aging Down syndrome (NiAD) database (niad.loni.usc.edu) and Alzheimer's Disease in Down Syndrome (ADDS) database. As such, the investigators within the ABC-DS study contributed to the design and implementation of ABC-DS and/or provided data but did not participate in analysis or writing of this report. A complete listing of ABC-DS investigators can be found at: https://www.nia.nih.gov/research/abc-ds#data. The Principal Investigators of the ABC-DS study are Benjamin Handen, PhD and William Klunk, MD, PhD, (University of Pittsburgh), Bradley Christian, PhD (University of Wisconsin-Madison), Nicole Schupf, PhD, Dr PH (Columbia University), and Ira Lott, MD and Wayne Silverman, PhD (UC Irvine). The ABC-DS study is a collaboration of field sites at Pittsburgh, Madison, Phoenix (Banner Alzheimer's Institute; Marwan Sabbagh, MD), the University of Cambridge (Shahid Zaman, MD), Washington University (Beau Ances, MD, PhD and John Constantino, MD), Columbia University, Harvard University (Florence Lai, MD and H Diana Rosas, MD) and UC Irvine. ABC-DS was established to collect longitudinal clinical, neuroimaging, genetic and biofluid markers in approximately 400 participants with DS who were primarily non-demented.

Abstract: Background:Virtually all adults with Down syndrome (DS) develop Alzheimer’s disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS. Objective:The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (–versus+) and/or decline in memory and mental status were associated with weight loss prior to AD progression. Methods:Analyses included 261 adults with DS. PET data were acquired using [11C] PiB for Aβ and [18F] AV-1451 for tau. Body mass index (BMI) was calculated from weight and height. Direct measures assessed dementia and memory. Clinical AD status was determined using a case consensus process. Percent weight decline across 16–20 months was assessed in a subset of participants (n = 77). Results:Polynomial regressions indicated an 0.23 kg/m2 decrease in BMI per year beginning at age 36.5 years, which occurs alongside the period during which Aβ and tau increase and memory and mental status decline. At a within-person level, elevated Aβ, decline in memory and mental status were associated with higher percent weight loss across 16–20 months. Conclusion:Unintentional weight loss occurs alongside Aβ deposition and prior to onset of AD dementia, and thus may be a useful sign of AD in DS.

Keywords: Alzheimer’s disease, amyloid, biomarkers, body mass index, tau, weight

DOI: 10.3233/JAD-220865

Journal: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1215-1227, 2023