Increased Dementia Risk in Older Adults With Down Syndrome

man with down syndrome on tablet
Nearly all older adults with Down syndrome now have dementia when they die, making this a vital population to study disease progression, modifying factors, and potential treatments.

In a study published in JAMA Neurology, dementia was associated with mortality in the majority of people with Down syndrome who are ≥36 years of age, with APOE ε4 carriers and those with multiple comorbid conditions displaying the highest risk for dementia and mortality.

Patient data were obtained from a prospective longitudinal study of cognition and health status of people in the United Kingdom with Down syndrome. A total of 211 people with Down syndrome age ≥36 years who had a mean length of 28.66 months of follow-up (range, 1-65 months) and a recorded dementia status were enrolled.

The main data collected during the study included dementia status, age, sex, APOE genotype, level of intellectual disability, health variables, and living situation. The investigators evaluated the association between Alzheimer’s disease and crude mortality as well as time to death and time to dementia diagnosis.

Of the 27 participants who died during follow-up, approximately 70% (n=19) had a clinical diagnosis of dementia. The crude mortality rates were 5 times higher for those with Down syndrome with dementia vs without dementia (1191.85 deaths/10,000 person-years [95% CI, 1168.49-1215.21] vs 232.22 deaths/10,000 person-years [95% CI, 227.67-236.77], respectively). In addition, those with dementia who were carriers of APOE ε4 had a 7-fold increased mortality risk compared with people with dementia who were not carriers of the genotype (hazard ratio [HR] 6.91; 95% CI, 1.756-27.195; P =.006).

An onset of epilepsy after 36 years of age was associated with an increased risk for mortality in patients without dementia (HR 9.66; 95% CI, 1.59-58.56; P =.01). Factors associated with an earlier dementia diagnosis in people with Down syndrome included carrying the APOE ε4 genotype (HR 4.92; 95% CI, 2.53-9.56; P <.001), early onset epilepsy (HR 3.61; 95% CI, 1.12-11.60; P =.03), having multiple health conditions (HR 1.96; 95% CI, 1.09-3.52; P =.03), and living with family (HR 2.14; 95% CI, 1.08-4.20; P =.03).

Limitations of the study include the small number of participants in the final cohort as well as the use of informant report for health data collection.

The investigators concluded by emphasizing their hope that their “findings can improve clinical care by identifying factors associated with increased risk for dementia and mortality risk in this population, suggesting the potentially beneficial effects of existing medication options and helping clinicians provide prognostic information for their patients with Down syndrome.”

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Hithersay R, Startin CM, Hamburg S, et al. Association of dementia with mortality among adults with Down syndrome older than 35 years [published online November 19, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.3616