Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England.
Division of Psychiatry, University College London, London, England.
JAMA Neurol. 2019 Feb 1;76(2):152-160. doi: 10.1001/jamaneurol.2018.3616.
This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS).
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.
Dementia status, age, sex, APOE genotype, level of intellectual disability, health variables, and living situation.
Crude mortality rates, time to death, and time to dementia diagnosis with proportional hazards of predictors.
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.
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.
这项工作量化了唐氏综合征（DS）患者中与阿尔茨海默病相关的痴呆的致命负担。
探讨与阿尔茨海默病相关的痴呆与死亡率的关系，并研究与 DS 成人痴呆相关的因素。
设计、地点和参与者：在英国社区环境中进行的前瞻性纵向研究。数据收集于 2012 年 3 月 29 日开始。病例于 2017 年 12 月 13 日截止。潜在样本包括伦敦唐氏综合征联合会队列中所有年龄在 36 岁及以上且有 2 次数据时间和痴呆状态记录的成年人（N=300）；6 人退出研究，28 人失访，55 人在分析时只有单次数据采集点。最终样本由 211 名参与者组成，随访时间为 503.92 人年。
痴呆状况、年龄、性别、APOE 基因型、智力障碍程度、健康变量和生活状况。
粗死亡率、死亡时间和痴呆诊断时间的比例风险预测因子。
在 211 名参与者中，96 名女性（45.5%），66 名（31.3%）有临床痴呆诊断。在研究期间有 27 名参与者（11 名女性；平均死亡年龄为 56.74 岁）死亡。70%的人患有痴呆症。痴呆患者的粗死亡率（1191.85 人年死亡人数/10000 人年；95%置信区间，1168.49-1215.21）是无痴呆患者的 5 倍（232.22 人年死亡人数/10000 人年；95%置信区间，227.67-236.77）。对于有痴呆的患者，APOE ε4 携带者的死亡风险增加了 7 倍（危险比 [HR]，6.91；95%置信区间，1.756-27.195）。对于没有痴呆的患者，36 岁以后发作的癫痫与死亡率相关（HR，9.66；95%置信区间，1.59-58.56）。APOE ε4 携带者（HR，4.91；95%置信区间，2.53-9.56）、早发性癫痫患者（HR，3.61；95%置信区间，1.12-11.60）、多种健康合并症（HR，1.956；95%置信区间，1.087-3.519）和与家人同住的患者（HR，2.14；95%置信区间，1.08-4.20）更早地被诊断为痴呆。
在 70%的老年 DS 患者中，痴呆与死亡率相关。APOE ε4 携带者和/或患有多种合并症的患者患痴呆和死亡的风险增加，这突出了需要良好的医疗保健。对于那些没有痴呆诊断就死亡的患者，迟发性癫痫是唯一与死亡相关的重要因素，这引发了对该组中潜在未确诊痴呆病例的质疑。
