As more people with Down syndrome live longer, many of them are developing and dying from Alzheimer’s disease-related dementia. In fact, a study published online in JAMA Neurology on November 19 shows that seven out of 10 adults with Down syndrome die from the condition.
About 80 percent of people with Down syndrome older than 65 have Alzheimer’s disease. The prevalence is due to a tripling of the amyloid precursor protein (APP) gene, which controls production of the protein amyloid, on chromosome 21. People with Down syndrome have an extra copy of chromosome 21 and with it a high accumulation of amyloid plaques in their brains, which may lead to young-onset dementia.
To determine how dementia and co-existing health problems such as epilepsy and respiratory problems affect mortality rates in patients with Down syndrome, a team of researchers analyzed data from 211 adults aged 36 years and older from the London Down Syndrome Consortium. This long-term study aims to determine the risk and protective factors for developing dementia in people with Down syndrome.
Slightly less than half of the participants were female, and 31.3 percent had a clinical dementia diagnosis from the patients' regular clinicians after a comprehensive assessment. Researchers interviewed the participants’ caregivers to obtain medical histories, including co-existing conditions such as early-onset (before age 20 years) and late-onset (older than 36 years) epilepsy, hypothyroidism, congenital heart defects, and cataracts. The researchers also collected information on dementia and antipsychotic medications and confirmed participants’ APOE genotype based on a blood or saliva sample.
During the study period, 27 participants died, with an average age of death of 56.7 years; 70 percent of the deceased had dementia. Mortality rates were five times higher in adults with Down syndrome who also had dementia: 28.8 percent in the dementia group versus 5.5 percent in the group without dementia. However, participants who had late-onset epilepsy without a diagnosis of dementia had a tenfold increased mortality risk. The researchers hypothesized that some of these patients may have had undiagnosed dementia.
Down syndrome patients with dementia who carried at least one APOE ε4 alleles had about seven times increased risk of death. No sex differences in mortality were found.
Overall, adults with APOE ε4 genotype, early-onset epilepsy, multiple health comorbidities, and those living with family were diagnosed with dementia significantly earlier. The researchers concluded that the earlier diagnoses were most likely due to more interaction with health care services because of other health conditions and aware family members noticing changes rather than an increased risk or incidence of dementia.
Identifying and treating common health problems among people with Down syndrome is important because having additional health conditions was associated with an increased risk of dementia and death in those with dementia diagnoses.
Determining all the risk factors that increase dementia and death in adults with Down syndrome may result in better care and appropriate medication for co-existing conditions. It may also help physicians provide more specific information about prognosis.
The researchers said more clinical trials that focus on treatments to prevent or delay dementia in those with Down syndrome are warranted.