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Dementia linked to increased mortality risk in adults with Down syndrome

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“Astonishing” findings suggest need for planning, evaluation

Although this prospective longitudinal study has a limited sample size and short follow-up, the finding that dementia is the proximate cause of death in approximately 70% of individuals with Down syndrome was “astonishing,” Michael S. Rafii, MD, PhD, and Stephanie L. Santoro, MD, wrote in an editorial.

Mortality rates among individuals with Down syndrome were five times higher in those with dementia as compared with those without dementia in this study, with a median age at death of 57 years (see article).

“By comparison, in the general population, dementia of any subtype is listed in only 18% of death certificates for those older than 65 years, with mortality rates being slightly less than twofold higher in those with dementia than those without,” Dr. Rafiii and Dr. Santoro wrote in their editorial.

Results of the study imply that most older individuals with Down syndrome will have dementia at the time of death, which suggests that these individuals and their families have a “greater need” to plan for a life stage that includes dementia, the authors said.

Physicians and health care systems could consider screening for dementia and epilepsy as part of their standard care practices for older adults with Down syndrome based on these study results, they added.

“Although consensus guidelines and screening tools have been published for the evaluation and management of dementia in Down syndrome, it remains unclear if there has been widespread implementation of these,” the authors said.

Dr. Rafii is with the Alzheimer’s Therapeutic Research Institute at the University of Southern California, San Diego. Coauthor Dr. Santoro is with the Down Syndrome Program at Massachusetts General Hospital and with Harvard Medical School, both in Boston. The authors reported no conflict of interest disclosures related to their editorial, which appears in JAMA Neurology .



Adults with Down syndrome and dementia had a risk of death five times higher than those without dementia, according to results of a recent prospective study.

Rosalyn Hithersay

More than 70% of the individuals with Down syndrome who died over the course of follow-up had a clinical diagnosis of dementia in this longitudinal study of community dwelling participants, many of whom had factors associated with dementia such as the apolipoprotein E (APOE) genotype.

The findings of this study support an “urgent need” for clinical trials of treatment that might delay or prevent dementia in individuals with Down syndrome, said the investigators, led by Rosalyn Hithersay, MSc, of the department of forensic and neurodevelopmental sciences in the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London (United Kingdom).

“We hope that our 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,” the authors wrote in JAMA Neurology.

The risk of dementia in individuals with Down syndrome has grown to “exceptional” levels, alongside a dramatic increase in life expectancy in these patients, from just 10 years of age some 50 years ago, to nearly 64 years today, investigators said.

Although other research has confirmed that dementia is frequently recorded as a contributory factor in Down syndrome deaths in recent years, this latest study provides crude mortality rates and exploratory analyses of factors that may modify mortality and dementia risk, according to the researchers.

Their study included 211 individuals with Down syndrome who were aged at least 36 years at study entry and followed for a total of 503.92 person-years, the investigators reported.

A total of 27 individuals died during follow-up, with a median age at death of 57 years; of those individuals, 19 (70.37%) had a clinical diagnosis of dementia, according to the report.

The crude mortality rate for individuals with dementia was nearly 1,192 deaths per 10,000 person-years, compared with 232 deaths per 10,000 person-years for those with no dementia diagnosis, the investigators found.

Further analysis showed that factors independently associated with mortality in those with a dementia diagnosis included APOE genotype, dementia medication status, early-onset epilepsy, and presence of two or more comorbid conditions.

In a combined model, APOE genotype was significantly associated with mortality risk, they added.

Among the eight individuals with Down syndrome who died without a dementia diagnosis, one reportedly had early signs of cognitive decline, and two had late-onset epilepsy.

Late-onset epilepsy, identified in seven individuals (4.8%) with no dementia diagnosis in this study, was the only factor associated with mortality in individuals without dementia, conferring a 10-fold increase in risk of that outcome, according to the analysis.

“This raises the question of whether seizures can begin in the absence of other features of dementia in individuals with Down syndrome or whether these seven individuals had significant AD pathology and neurological symptoms but had yet to receive a formal dementia diagnosis,” the researchers wrote in a discussion of results.

The authors reported no conflict of interest disclosures related to the study. Their research was supported by UK National Institute for Health Research networks and participating National Health Services trusts, as well as a Wellcome Trust Strategic Award to the London Down Syndrome Consortium.

SOURCE: Hithersay R et al. JAMA Neurol. 2018 Nov 19. doi: 10.1001/jamaneurol.2018.3616

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