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

Clina, J. G., Helsel, B. C., Hartley, S. L., White, D. A., Fleming-Batayneh, V. L., Handen, B., Christian, B., Head, E., Mapstone, M., Hom, C. L., Ances, B., Burns, J., Rosas, D., Lai, F., McHale, S. K., Lee, J. H., Schmitt, F. A., Harp, J., Lott, I. T., … Investigators, A. B. C. S. (2026). The impact of congenital heart disease on the timing of Alzheimer’s disease in Down syndrome.. Alzheimer’s & Dementia (Amsterdam, Netherlands), 18(1), e70257.

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 CHDNo 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 changesCHDs may influence the timing of Alzheimer's disease (AD) in adults with DS.

Last updated on 04/01/2026
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