Weight Loss and Alzheimer's Disease in Down Syndrome

J Alzheimers Dis. 2023;91(3):1215-1227. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / complications
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / etiology
  • Down Syndrome* / complications
  • Down Syndrome* / diagnostic imaging
  • Humans
  • Positron-Emission Tomography
  • Weight Loss
  • tau Proteins

Substances

  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers