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. 2019 Feb 1;76(2):152-160.
doi: 10.1001/jamaneurol.2018.3616.

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years

Rosalyn Hithersay  1   2   3 , Carla M Startin  1   2   3 , Sarah Hamburg  1   2   3 , Kin Y Mok  3   4   5 , John Hardy  3   4   6 , Elizabeth M C Fisher  3   7 , Victor L J Tybulewicz  3   8   9 , Dean Nizetic  3   10   11 , André Strydom  1   2   3
Affiliations

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years

Rosalyn Hithersay et al. JAMA Neurol. .

Abstract

Importance: This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS).

Objective: To explore the association of dementia associated with Alzheimer disease with mortality and examine factors associated with dementia in adults with DS.

Design, settings and participants: Prospective longitudinal study in a community setting in England. Data collection began March 29, 2012. Cases were censored on December 13, 2017. The potential sample consisted of all adults 36 years and older from the London Down Syndrome Consortium cohort with 2 data times and dementia status recorded (N = 300); 6 withdrew from study, 28 were lost to follow-up, and 55 had a single data collection point at time of analysis. The final sample consisted of 211 participants, with 503.92 person-years' follow-up.

Exposures: Dementia status, age, sex, APOE genotype, level of intellectual disability, health variables, and living situation.

Main outcomes and measures: Crude mortality rates, time to death, and time to dementia diagnosis with proportional hazards of predictors.

Results: Of the 211 participants, 96 were women (45.5%) and 66 (31.3%) had a clinical dementia diagnosis. Twenty-seven participants (11 female; mean age at death, 56.74 years) died during the study period. Seventy percent had dementia. Crude mortality rates for individuals with dementia (1191.85 deaths per 10 000 person-years; 95% CI, 1168.49-1215.21) were 5 times higher than for those without (232.22 deaths per 10 000 person-years; 95% CI, 227.67-236.77). For those with dementia, APOE ε4 carriers had a 7-fold increased risk of death (hazard ratio [HR], 6.91; 95% CI, 1.756-27.195). For those without dementia, epilepsy with onset after age 36 years was associated with mortality (HR, 9.66; 95% CI, 1.59-58.56). APOE ε4 carriers (HR, 4.91; 95% CI, 2.53-9.56), adults with early-onset epilepsy (HR, 3.61; 95% CI, 1.12-11.60), multiple health comorbidities (HR, 1.956; 95% CI, 1.087-3.519), and those living with family (HR, 2.14; 95% CI, 1.08-4.20) received significantly earlier dementia diagnoses.

Conclusions and relevance: Dementia was associated with mortality in 70% of older adults with DS. APOE ε4 carriers and/or people with multiple comorbid health conditions were at increased risk of dementia and death, highlighting the need for good health care. For those who died without a dementia diagnosis, late-onset epilepsy was the only significant factor associated with death, raising questions about potentially undiagnosed dementia cases in this group.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Cumulative Survival by Dementia Status
Kaplan-Meier survival curve for individuals with Down syndrome with dementia (n=66) and without dementia (n=145).
Figure 2.
Figure 2.. Proportional Hazards of Dementia Predictors
Hazard functions for variables associated with dementia diagnosis in Down syndrome.
See this image and copyright information in PMC

Comment in

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