The impact of congenital heart disease on the timing of Alzheimer's disease in Down syndrome

Authors

• Julianne G. Clina, University of KansasFollow
• Brian C. Helsel, University of Kansas
• Sigan L. Hartley, University of Wisconsin-Madison
• David A. White, Children's Mercy Hospitals and Clinics
• Victoria L. Fleming-Batayneh, University of Wisconsin-Madison
• Benjamin Handen, University of Pittsburgh
• Bradley Christian, University of Wisconsin-Madison
• Elizabeth Head, University of California Irvine
• Mark Mapstone, University of California Irvine
• Christy L. Hom, University of California Irvine
• Beau Ances, Washington University School of Medicine in St. Louis
• Jeffrey Burns, University of Kansas
• H. Diana Rosas, Harvard University
• Florence Lai, Harvard University
• Sharon Krinsky McHale, New York State Office for People with Developmental Disabilities
• Joseph H. Lee, Columbia University Medical Center
• Frederick A. Schmitt, University of KentuckyFollow
• Jordan Harp, University of KentuckyFollow
• Ira T. Lott, University of California Irvine
• Shahid Zaman, University of Cambridge
• Lauren T. Ptomey, University of Kansas

Abstract

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS. METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (n = 82, mean age = 39.9 ± 8.5 years, 97.6% White race) were age- and sex-matched to participants without CHD (n = 82, mean age = 40.5 ± 8.1 years, 98.8% White race). Cognitive assessments and Centiloid load (CL) (positron emission tomography) were compared by CHD status. RESULTS: People with CHD scored lower for visuospatial ability (β = −3.515, p = 0.022) but had higher CL (29.8 ± 12.8 vs. 39.8 ± 12.8, β = 8.00, p = 0.036) and were projected to hit Aβ positivity at a younger age (37.6 and 42.1 years). DISCUSSION: Presence of CHD may influence AD progression in DS. Highlights: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the threshold for an amyloid positivity at a younger age than those without CHD No differences in cognition were seen in the age- and sex-matched sample based on CHD status; however, the average age of the sample may be too young to see cognitive changes CHDs may influence the timing of Alzheimer's disease (AD) in adults with DS.

Document Type

Article

Publication Date

1-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.

Digital Object Identifier (DOI)

10.1002/dad2.70257

Archival?

Archival

Repository Citation

Clina, Julianne G.; Helsel, Brian C.; Hartley, Sigan L.; White, David A.; Fleming-Batayneh, Victoria L.; Handen, Benjamin; Christian, Bradley; Head, Elizabeth; Mapstone, Mark; Hom, Christy L.; Ances, Beau; Burns, Jeffrey; Rosas, H. Diana; Lai, Florence; McHale, Sharon Krinsky; Lee, Joseph H.; Schmitt, Frederick A.; Harp, Jordan; Lott, Ira T.; Zaman, Shahid; and Ptomey, Lauren T., "The impact of congenital heart disease on the timing of Alzheimer's disease in Down syndrome" (2026). Neurology Faculty Publications. 153.
https://uknowledge.uky.edu/neurology_facpub/153