Effects of Age on the Association between Down Syndrome and Common Disease Conditions
- 1Advocate Health
Abstract
ImportanceAge-based screening and prevention guidelines in healthcare are developed largely in populations without Down syndrome (DS). If disease risk among individuals with DS differs significantly relative to typically developing (TD) individuals of similar ages, standard guidelines may overlook critical windows of care.
ObjectiveTo determine the age-specific risk of ten common conditions in individuals with DS compared to a matched TD cohort to evaluate the presence of risk modification by age.
DesignRetrospective longitudinal cohort study.
SettingMidwest healthcare system.
Participants4,912 individuals with DS and 37,924 TD controls, with clinical encounters between January 2005 and May 2025. Total person years (PYs) were 25,896 and 149,078 respectively.
ExposureDS status
Main Outcomes and MeasuresIncidence of acute sinusitis, anxiety, asthma, depression, gastroesophageal-reflux disorder, nervous system disorders, respiratory failure, thyroid gland disorders, vasomotor/allergic rhinitis, and vitamin-D deficiency. Incidence rate ratios (IRR) trajectories were analyzed using generalized additive mixed models. Wald tests assessed the presence of age modification.
ResultsIn our DS cohort (medianage: 24, 48% female), we found evidence of age-related risk modification in 6 of 10 conditions examined. The relative incidence of anxiety was significantly lower among individuals with DS in early childhood (at age 5, IRR 0.23, 95%CI 0.19-0.29), compared to TD controls of the same age. However, risk in the DS cohort increased with age approaching equal levels with controls around ages 65. Similar trends were observed for depression. The association between DS and gastroesophageal disease was largely null except between ages 1-8, where the incidence among DS cohort was elevated (5-7 cases per 1000 PYs) compared to controls (2-3 cases per 1000 PYs). The association between DS and respiratory failure was statistically insignificant until age 53-70, where incidence among individuals with DS rose sharply (13-30 cases per 1000 PYs), while for TD counterparts it remained constant at 8-9 cases per 1000 PYs. Lastly, risk of vitamin-D deficiency fluctuated with a peak at age 20 (IRR 2.34, 95%CI2.02-2.72).
Conclusions and RelevanceThese findings demonstrate age effect modification among individuals with DS across a variety of disease conditions and highlight the importance of population-specific care guidelines.
Key PointsO_ST_ABSQuestionC_ST_ABSDoes risk of disease vary significantly between individuals with Down syndrome and typically developing individuals by age?
FindingsRisks of anxiety, depression, thyroid gland disease, gastroesophageal disease, respiratory failure, and vitamins D deficiency varied significantly by age among individuals with Down syndrome, compared to a typically developing matched cohort.
MeaningThis manuscript describes key differences in age trajectories for different conditions experienced by individuals with Down syndrome. Previous disconnects in our understanding of age at diagnosis have likely led to mistimed and/or missed screening and prevention opportunities in individuals with Down Syndrome when following guidelines for typically developing counterparts.
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BibTeX
@misc{noah2026effects,
title = {{Effects of Age on the Association between Down Syndrome and Common Disease Conditions}},
author = {A. Noah and H. Tavalire and V. Fitzpatrick and H. Graham and S. Verma and L. Krohn and K. Frank and D. Vockeroth and B. Chicoine},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.26362053},
url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26362053v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Effects of Age on the Association between Down Syndrome and Common Disease Conditions
AU - A. Noah
AU - H. Tavalire
AU - V. Fitzpatrick
AU - H. Graham
AU - S. Verma
AU - L. Krohn
AU - K. Frank
AU - D. Vockeroth
AU - B. Chicoine
PY - 2026
DA - 2026/09/02
PB - medRxiv
DO - 10.64898/2026.09.02.26362053
UR - https://www.medrxiv.org/content/10.64898/2026.09.02.26362053v1
AB - ImportanceAge-based screening and prevention guidelines in healthcare are developed largely in populations without Down syndrome (DS). If disease risk among individuals with DS differs significantly relative to typically developing (TD) individuals of similar ages, standard guidelines may overlook critical windows of care. ObjectiveTo determine the age-specific risk of ten common conditions in individuals with DS compared to a matched TD cohort to evaluate the presence of risk modification by age. DesignRetrospective longitudinal cohort study. SettingMidwest healthcare system. Participants4,912 individuals with DS and 37,924 TD controls, with clinical encounters between January 2005 and May 2025. Total person years (PYs) were 25,896 and 149,078 respectively. ExposureDS status Main Outcomes and MeasuresIncidence of acute sinusitis, anxiety, asthma, depression, gastroesophageal-reflux disorder, nervous system disorders, respiratory failure, thyroid gland disorders, vasomotor/allergic rhinitis, and vitamin-D deficiency. Incidence rate ratios (IRR) trajectories were analyzed using generalized additive mixed models. Wald tests assessed the presence of age modification. ResultsIn our DS cohort (medianage: 24, 48% female), we found evidence of age-related risk modification in 6 of 10 conditions examined. The relative incidence of anxiety was significantly lower among individuals with DS in early childhood (at age 5, IRR 0.23, 95%CI 0.19-0.29), compared to TD controls of the same age. However, risk in the DS cohort increased with age approaching equal levels with controls around ages 65. Similar trends were observed for depression. The association between DS and gastroesophageal disease was largely null except between ages 1-8, where the incidence among DS cohort was elevated (5-7 cases per 1000 PYs) compared to controls (2-3 cases per 1000 PYs). The association between DS and respiratory failure was statistically insignificant until age 53-70, where incidence among individuals with DS rose sharply (13-30 cases per 1000 PYs), while for TD counterparts it remained constant at 8-9 cases per 1000 PYs. Lastly, risk of vitamin-D deficiency fluctuated with a peak at age 20 (IRR 2.34, 95%CI2.02-2.72). Conclusions and RelevanceThese findings demonstrate age effect modification among individuals with DS across a variety of disease conditions and highlight the importance of population-specific care guidelines. Key PointsO_ST_ABSQuestionC_ST_ABSDoes risk of disease vary significantly between individuals with Down syndrome and typically developing individuals by age? FindingsRisks of anxiety, depression, thyroid gland disease, gastroesophageal disease, respiratory failure, and vitamins D deficiency varied significantly by age among individuals with Down syndrome, compared to a typically developing matched cohort. MeaningThis manuscript describes key differences in age trajectories for different conditions experienced by individuals with Down syndrome. Previous disconnects in our understanding of age at diagnosis have likely led to mistimed and/or missed screening and prevention opportunities in individuals with Down Syndrome when following guidelines for typically developing counterparts.
ER -