Weight Loss and Alzheimer's Disease in Down Syndrome

Victoria Fleming^{1

2}, Brian C Helsel³, Lauren T Ptomey⁴, H Diana Rosas⁵, Benjamin Handen⁶, Charles Laymon^{7

8}, Bradley T Christian¹, Elizabeth Head⁹, Mark Mapstone¹⁰, Florence Lai^{9

11}, Sharon Krinsky-McHale¹², Shahid Zaman¹³, Beau M Ances¹⁴, Joseph H Lee¹⁵, Sigan L Hartley^{1

2}; Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS) Consortium

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
² School of Human Ecology, University of Wisconsin-Madison, WI, USA.
³ Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
⁴ Departmentof Internal Medicine, University of Kansas Medical Center, KansasCity, KS, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
¹⁰ Department of Neurology, University of California Irvine, Irvine, CA, USA.
¹¹ Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
¹² Department of Psychology, New York Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
¹³ Department of Psychiatry, Clinical School, University of Cambridge, Cambridge, UK & Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, UK.
¹⁴ Department of Neurology, Washington University Saint Louis, St. Louis, MO, USA.
¹⁵ 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.

PMID: 36565120
PMCID: PMC9940268
DOI: 10.3233/JAD-220865

Weight Loss and Alzheimer's Disease in Down Syndrome

Victoria Fleming et al. J Alzheimers Dis. 2023.

. 2023;91(3):1215-1227.

doi: 10.3233/JAD-220865.

Authors

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
² School of Human Ecology, University of Wisconsin-Madison, WI, USA.
³ Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
⁴ Departmentof Internal Medicine, University of Kansas Medical Center, KansasCity, KS, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
¹⁰ Department of Neurology, University of California Irvine, Irvine, CA, USA.
¹¹ Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
¹² Department of Psychology, New York Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
¹³ Department of Psychiatry, Clinical School, University of Cambridge, Cambridge, UK & Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, UK.
¹⁴ Department of Neurology, Washington University Saint Louis, St. Louis, MO, USA.
¹⁵ 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.

PMID: 36565120
PMCID: PMC9940268
DOI: 10.3233/JAD-220865

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.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflict of interest to report.

Figures

**Fig. 1.**
Polynomial effect of age on body mass index (BMI), Alzheimer’s disease (AD) pathology, and cognitive decline.

**Fig. 2.**
Percent weight loss by PET Biomarker Status (left) and by clinical status (right).

**Fig. 3.**
Percent weight loss by PET biomarker status and change in mental status in cognitively stable adults with Down syndrome.

See this image and copyright information in PMC

References

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Weight Loss and Alzheimer's Disease in Down Syndrome

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Weight Loss and Alzheimer's Disease in Down Syndrome

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Conflict of interest statement

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