HAI Book 2025 - Flipbook - Page 642
Yau, Wai-Ying Wendy
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Amyloid modifies the association between late-life BMI and
longitudinal cognition in cognitively unimpaired individuals
Wai-Ying Wendy Yau1,2, Rema Raman3, Shunran Wang3, Neelum Aggarwal4, Adam Brickman5,
Jasmeer Chhatwal1,2,6, Petrice Cogswell7, Jonathan Graff-Radford7, Jay Pillai7, Michael Rafii3,
Paul Aisen3, Reisa Sperling1,2,6, The A4 and Learn Study Teams8
1
Massachusetts General Hospital, Boston, MA, US
Harvard Medical School, Boston, MA, US
3
University of Southern California, San Diego, CA, US
4
Rush University Medical Center, Chicago, IL, US
5
Columbia University, New York, NY, US
6
Brigham and Women’s Hospital, Boston, MA, US
7
Mayo Clinic, Rochester, NY, US
8
Alzheimer Clinical Trials Consortium, https://www.actcinfo.org/a4-Study- Team-Lists/, US
2
Background: Midlife obesity is linked to increased risk of Alzheimer's disease (AD), but the relationship between
late-life obesity and AD is less clear. Given growing interest in combination prevention trials targeting amyloid and
vascular risk factors in older individuals, it is critical to understand how late-life BMI and amyloid burden may
interact to influence cognitive decline.
Methods: We examined 1668 baseline cognitively unimpaired participants across A4 and LEARN (age 71.5±4.7,
59.9% female, amyloid 47±40 Centiloid, BMI 28±5). Cognition was assessed longitudinally (4.1±1.5 years) using the
Preclinical Alzheimer Cognitive Composite (PACC). We examined for interactive effects between baseline BMI and
amyloid burden (18F-Florbetapir PET) on cross-sectional (linear regression) and longitudinal (natural cubic spline
model) cognition, adjusting for age, sex, education, APOE4, cognitive test version, and study/treatment.
Results: At baseline, higher BMI was associated with lower PACC scores (Standardized ´=-0.13, p=0.02; Figure 1),
with no interaction between BMI and amyloid on baseline cognition (p=0.70). Longitudinally, we identified a
significant interaction between baseline BMI and amyloid burden on cognitive decline (p
