Symptom onset, mortality linked for those with Down syndrome, autosomal dominant AD
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Age variability in symptom onset of Alzheimer’s disease in those with Down syndrome was comparable to those who experienced autosomal dominant AD, while mortality was also similar, according to a study published in JAMA Network Open.
“Down syndrome is a complex condition with multiple associated comorbidities that vary throughout the lifespan. Improvements in health care ... have increased life expectancy from approximately 5 years in the 1950s to roughly 60 years in the 2020s,” Maria Florencia Iulita, PhD, of the Center for Biomedical Investigation Network for Neurodegenerative Diseases, Madrid, and colleagues wrote. “A consequence of this increased life expectancy has been the emergence of age-related diseases, most importantly Alzheimer’s disease, which has a risk of more than 90% by the seventh decade.”
Researchers aimed to assess whether variability in AD symptom onset in those with Down syndrome is similar to autosomal AD and to examine its association with mortality.
The study combined meta-analysis and used mortality data from U.S. death certificates to include 77,347 records (49% female) with an ICD classification for Down syndrome between 1968 to 2019, as well as a longitudinal cohort study from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI), which included 889 individuals (46% female).
Meta-analysis was engaged to examine the age at onset, age at death and duration of AD-related dementia in those with Down syndrome. PubMed/Medline, Embase, Web of Science, and CINAHL databases were accessed for research reports, whereas OpenGray was used for gray literature. Pooled estimates with corresponding 95% CIs were calculated using random-effects meta-analysis. Variability in disease onset was compared with autosomal dominant AD. Based on these estimates, a hypothetical distribution of age at death was constructed, assuming fully penetrant AD. These results were compared with real-world mortality data.
Results showed the estimate of age at onset was 53.8 years (95% CI, 53.1-54.5 years; n=2,695); estimate of age at death, 58.4 years (95% CI, 57.2-59.7 years; n=324); and the estimate of disease duration, 4.6 years (95% CI, 3.7-5.5 years; n=226). Coefficients of variation and 95% prediction intervals of age at onset were comparable with those reported in autosomal dominant AD.
In addition, U.S. mortality data revealed an increase in life expectancy in Down syndrome from a median of 1 year in 1968 to 57 years in 2019. The mortality data matched the limits projected by a distribution assuming fully penetrant AD in up to 80% of deaths. This contrasts with dementia mentioned in 30% of death certificates but agrees with the mortality data found in DABNI (78.9%).
“Our study underscores that Alzheimer’s disease has the same variability in age at onset in Down syndrome and autosomal dominant pedigrees,” Iulita and colleagues wrote.