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Dementia was the proximate cause of death in 70% of adults with Down syndrome over 35 years old, according to a prospective longitudinal study in England.

APOE ε4 carriers and people with multiple co-morbid health conditions were most at risk for dementia and death, reported Rosalyn Hithersay, MSc, of King's College London, and colleagues in .

"We have known for some time that people with Down syndrome are at increased risk of developing dementia due to Alzheimer's disease," Hithersay told 木瓜直播. "Our new research quantifies this risk and shows that dementia is now very closely linked to mortality in this population."

Fifty years ago, life expectancy for people with Down syndrome was only 10 years, with congenital heart defects responsible for most deaths within the first year.

"With advances in medical care and improvements in the overall health of individuals with Down syndrome, life expectancy has increased dramatically; for children with Down syndrome born in 2010, median life expectancy is estimated to be 65 years," observed Michael Rafii, MD, PhD, of the Keck School of Medicine of the University of Southern California in San Diego, and Stephanie Santoro, MD, of Harvard 木瓜直播 School in Boston, in an .

But with this longer life span comes the prospect of a considerable increase in the risk of developing dementia associated with Alzheimer disease -- a prevalence of of Down syndrome patients older than age 65, they added.

In this study, Hithersay and co-authors followed 211 adults with Down syndrome age 35 years and older in England for up to 65 months. Of the 211 participants, 45.5% were female and 31.3% (n=66) had a clinical dementia diagnosis.

In the study period, 27 participants died, with a mean age of death of 56.7 years; 70% of these people had dementia. Mortality rates were 5 times higher in adults with Down syndrome and dementia (28.8% in the dementia group versus 5.5% in the group without dementia).

"By comparison, in the general population, dementia of any subtype is listed in for those older than 65 years, with mortality rates being slightly less than in those with dementia than those without," noted Rafii and Santoro.

Down syndrome adults with dementia who carried at least one APOE ε4 allele had a 7-fold increased risk of death (HR 6.91; 95% CI 1.76-27.20). No sex differences in mortality were apparent, but late-onset epilepsy increased mortality risk in Down syndrome adults without dementia 10-fold (HR 9.66; 95% CI 1.59-58.56).

Adults with APOE ε4 genotype, early-onset epilepsy, multiple health comorbidities, and those living with family received significantly earlier dementia diagnoses. "One important finding for clinicians is that people with two or more co-morbid health conditions were more likely to develop dementia at an earlier age," Hithersay said. Many of the conditions were treatable, she noted: "As awareness of the increased risk of dementia in Down syndrome increases, we must also make sure that this knowledge does not overshadow other health problems in these adults."

The study has several limitations, Hithersay and colleagues noted. The sample was drawn from the London Down Syndrome Consortium cohort and while it is large for its detail, it is relatively small for an epidemiologic study. In addition, health information was collected through informant reports, which may have been influenced by recall and other forms of bias.