HAI Book 2025 - Flipbook - Page 585
Smith, Anna
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Multi-morbidity and Alzheimer9s disease pathology across the
lifespan in adults with Down syndrome
Anna Smith1, Natalie Edwards1, Lisi Flores Aguilar3, Mohamad Alshikho1, Dana Tudorascu4, H.
Diana Rosas6, Michael Yassa3, Sigan L Hartley2, Benjamin Handen4, Bradley Christian2, Jose
Gutierrez1, Donna Wilcock5, Elizabeth Head3, Adam M Brickman1, Patrick Lao1
1
Columbia University Medical Center, New York, NY, US
University of Wisconsin-Madison, Madison, WI, US
3
University of California-Irvine, Irvine, CA, US
4
University of Pittsburgh, Pittsburgh, PA, US
5
Indiana University, Indianapolis, IN, US
6
Harvard University, Boston, MA, US
2
Introduction: People with Down syndrome (DS) have greater risk for certain health conditions compared to the
non-DS population, and comorbid contributions to Alzheimer9s disease (AD) biomarker developments need to be
better understood even in the context of genetic risk. We took a hypothesis-generating approach to explore
whether comorbidities are associated with age-related trajectories of AD and cerebrovascular biomarkers in
adults with DS.
Methods: Adults with DS (n=259; 45±10 yrs, 43% women, 75% Cognitively-Stable/12% MCI-DS/13%ADDS/excluded Unable to Determine) from the Alzheimer9s Biomarker Consortium-Down syndrome (ABC-DS)
underwent MRI (white matter hyperintensity (WMH), enlarged perivascular space (PVS), infarcts, microbleeds),
amyloid PET (Florbetapir Centiloids), and tau PET (AV-1451 SUVR). Comorbid conditions were collected from
participant9s health history. Biomarkers were fit against left-null piecewise regression models with age, adjusting
for acquisition parameters across the multisite study. The age-trajectory residuals for each biomarker were then
regressed on each comorbidity (i.e., more/less than expected for their age/disease progression).
Results: Congenital heart disease, hypotension, diabetes, sleep apnea, pneumonia, hyperlipidemia, and
hypothyroidism were present, but had no associations with biomarker trajectories (Table 1). As previously
reported, hypertension was associated with a greater PVS, and lower BMI was associated with greater WMH.
Hypertension was further associated with lower early Braak tau. Seizures were associated with greater
microbleed likelihood. Visual impairment was associated with greater infarct likelihood, while cataracts were
associated with lower tau across Braak stages and lower PVS; hearing impairment was associated with lower late
Braak tau. No comorbidity was associated with amyloid.
Conclusion: In adults with DS, common comorbidities were not associated with amyloid, suggesting that APP
overproduction is a strong driver of amyloid trajectory, approximated by chronological age. Seizures and visual
impairment may be related to cerebrovascular burden, and reverse causality is possible. Comorbidity
duration/severity/treatment, multimorbidity, AD diagnosis, and selection bias may clarify these patterns.
HAI2025 - 585
