Immediate and Underlying Causes of Death and Survival Rates in Aging Adults With Down Syndrome.
T I M Hilgenkamp, A Oppewal, L C Chien and 1 others
Among matched adults aged 50 and over, Down syndrome carried a 5.05-times higher risk of death over 10 years.
Respiratory disease was the top immediate cause, but dementia was the leading underlying cause.
Key findings
1After adjusting for age, sex, and intellectual disability level, Down syndrome was associated with a 5.05-times higher hazard of death (95% CI 3.10 to 7.47, p < 0.001) compared with matched adults without Down syndrome.
2Respiratory diseases and infections were the most common immediate and underlying causes of death in both groups. In the Down syndrome group, neuropsychiatric conditions (13 from dementia/Alzheimer's, 6 from epilepsy) were the second underlying cause at 17.75%.
3Neuropsychiatric conditions accounted for 17.75% of underlying deaths in the Down syndrome group versus 2.08% in the matched comparison group (p = 0.008), a difference that was significant for underlying causes but not for immediate causes (p = 0.070).
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What it does not show
A substantial proportion of deaths had missing or ill-defined causes (27.10% immediate, 24.30% underlying in the Down syndrome group; 39.58% and 37.50% in the comparison group), so the true distribution of causes, particularly cardiovascular, may be misestimated. The cohort includes only adults receiving formal care or support in the Netherlands, so it may not represent adults with Down syndrome who are not in contact with formal services. This is an observational cohort study; the 5.05-times higher hazard is an association, not proof that Down syndrome causes the excess mortality. The high proportion of missing data differs between groups (higher in the comparison group), which may partly drive the observed between-group differences in cause-specific mortality rather than reflecting true etiological differences.
Declared interests
Funded by the National Institute on Aging (R03AG078730) and the HA-ID care organizations (Abrona, Amarant, Ipse de Bruggen) and the Department of General Practice, Intellectual Disability Medicine Research at Erasmus MC. The authors state the funding sources were not involved in the conduct of the research or preparation of the manuscript. The authors declare no conflicts of interest.
The easy way to misread this
Do not read the similar cardiovascular death rates (6.54% in the Down syndrome group versus 6.25% in the comparison group) as evidence that Down syndrome does not increase cardiovascular risk. The authors note that 27.10% of immediate causes were missing in the Down syndrome group, and they cite data showing 80% of unexplained deaths in the general population are cardiovascular, so the true contribution is likely higher than the recorded figure.
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