Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome.
Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome.
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DOI：
10.1001/jamanetworkopen.2022.12910
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发表时间：
2022-05-02
影响因子：
13.8
通讯作者：
中科院分区：
文献类型：
--
作者：
这项荟萃分析评估了唐氏综合征中阿尔茨海默病症状发作的变异性是否与常染色体显性阿尔茨海默病相似及其与死亡率的相关性。唐氏综合征患者阿尔茨海默病的发病年龄是否与常染色体显性遗传形式一致，该疾病与死亡率的相关性是否与接近完全痴呆一致？在这项荟萃分析和队列研究中，唐氏综合征症状发作时年龄的变异性与常染色体显性遗传阿尔茨海默病相当。死亡率数据和一致的发病年龄与完全渗透性阿尔茨海默病相符。这些发现表明，缩小唐氏综合征患者与普通人群的预期寿命差距需要有效预防或管理阿尔茨海默病。患有唐氏综合症的人患阿尔茨海默病痴呆症的风险很高。然而，发病率和年龄被认为是可变的，这种疾病与预期寿命的关系仍然不清楚，因为死亡证明中的报告不足。评估唐氏综合征阿尔茨海默病症状发作的变异性是否与常染色体显性阿尔茨海默病相似，并评估其与死亡率的相关性。这项研究结合了荟萃分析和对美国死亡证明中死亡率数据的评估（n = 77347例病例记录，1968年至2019年期间国际疾病分类编码为唐氏综合征; 37900例[49%]女性）和一项纵向队列研究（n = 889人; 46%女性; 3.2 [2.1]年随访）来自Down Alzheimer Barcelona Neuroimaging Initiative（DABNI）。进行了一项荟萃分析，以调查唐氏综合征患者的发病年龄、死亡年龄和阿尔茨海默病痴呆持续时间。检索PubMed/Medline、Embase、Web of Science和CINAHL的研究报告，使用OpenGray检索灰色文献。纳入了关于发病或诊断年龄、死亡年龄和疾病持续时间的研究。使用随机效应荟萃分析计算合并估计值及相应的95% CI。疾病发作的变异性与常染色体显性阿尔茨海默病进行了比较。基于这些估计，假设完全渗透性阿尔茨海默病，构建了一个假设的死亡年龄分布。这些结果与真实世界的死亡率数据进行了比较。在这项荟萃分析中，估计发病年龄为53.8岁（95% CI，53.1-54.5岁; n = 2695）;死亡年龄估计值，58.4岁（95% CI，57.2-59.7年; n = 324）;疾病持续时间估计值为4.6年（95% CI，3.7-5.5年; n = 226）。发病年龄的变异系数和95%预测区间与常染色体显性遗传阿尔茨海默病的报道相当。美国死亡率数据显示，唐氏综合征患者的预期寿命有所增加（中位数[IQR]，1968年为1 [0.3-16]岁，2019年为57 [49-61]岁），但在过去几十年中，死亡年龄最高的人群具有明显的天花板效应（第90百分位数：1990年，63岁; 2019年，65岁）。死亡率数据与假设高达80%的死亡（对应于最高百分位数）完全渗透阿尔茨海默病的分布预测的极限相匹配。这与30%的死亡证明中提到的痴呆症形成对比，但与DABNI的死亡率数据（78.9%）一致。重要的种族差异在2019年持续存在，在较低的年龄组（第10百分位：黑人个体，1岁;白色个体，30岁）中比在较高的年龄组（第90百分位：黑人个体，64岁;白色个体，66岁）中更为明显。这些发现表明，死亡率数据和一致的发病年龄与完全渗透性阿尔茨海默病相一致。唐氏综合症患者的寿命不会增加，直到阿尔茨海默病的疾病改善治疗可用。
This meta-analysis assesses whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and its association with mortality. Is age at onset of Alzheimer disease in people with Down syndrome as consistent as in autosomal dominant forms, and is the association of the disease with mortality compatible with near full penetrance? In this meta-analysis and cohort study, the variability of age at symptom onset in Down syndrome was comparable to autosomal dominant Alzheimer disease. The mortality data and the consistent age at onset were compatible with fully penetrant Alzheimer disease. These findings suggest that closing the life expectancy gap for individuals with Down syndrome compared with the general population will require effective prevention or management of Alzheimer disease. People with Down syndrome have a high risk of developing Alzheimer disease dementia. However, penetrance and age at onset are considered variable, and the association of this disease with life expectancy remains unclear because of underreporting in death certificates. To assess whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and to assess its association with mortality. This study combines a meta-analysis with the assessment of mortality data from US death certificates (n = 77 347 case records with a International Classification of Diseases code for Down syndrome between 1968 to 2019; 37 900 [49%] female) and from a longitudinal cohort study (n = 889 individuals; 46% female; 3.2 [2.1] years of follow-up) from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI). A meta-analysis was conducted to investigate the age at onset, age at death, and duration of Alzheimer disease dementia in Down syndrome. PubMed/Medline, Embase, Web of Science, and CINAHL were searched for research reports, and OpenGray was used for gray literature. Studies with data about the age at onset or diagnosis, age at death, and disease duration were included. Pooled estimates with corresponding 95% CIs were calculated using random-effects meta-analysis. The variability in disease onset was compared with that of autosomal dominant Alzheimer disease. Based on these estimates, a hypothetical distribution of age at death was constructed, assuming fully penetrant Alzheimer disease. These results were compared with real-world mortality data. In this meta-analysis, the estimate of age at onset was 53.8 years (95% CI, 53.1-54.5 years; n = 2695); the 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 Alzheimer disease. US mortality data revealed an increase in life expectancy in Down syndrome (median [IQR], 1 [0.3-16] years in 1968 to 57 [49-61] years in 2019), but with clear ceiling effects in the highest percentiles of age at death in the last decades (90th percentile: 1990, age 63 years; 2019, age 65 years). The mortality data matched the limits projected by a distribution assuming fully penetrant Alzheimer disease in up to 80% of deaths (corresponding to the highest percentiles). This contrasts with dementia mentioned in 30% of death certificates but is in agreement with the mortality data in DABNI (78.9%). Important racial disparities persisted in 2019, being more pronounced in the lower percentiles (10th percentile: Black individuals, 1 year; White individuals, 30 years) than in the higher percentiles (90th percentile: Black individuals, 64 years; White individuals, 66 years). These findings suggest that the mortality data and the consistent age at onset were compatible with fully penetrant Alzheimer disease. Lifespan in persons with Down syndrome will not increase until disease-modifying treatments for Alzheimer disease are available.
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影响因子：
5.3
作者：
Firth NC;Startin CM;Hithersay R;Hamburg S;Wijeratne PA;Mok KY;Hardy J;Alexander DC;LonDownS Consortium;Strydom A
通讯作者：
Strydom A
影响因子：
4.2
作者：
Coppus, Antonia M. W.;Schuur, Maaike;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.
影响因子：
5.1
作者：
Cosgrave, MP;Tyrrell, J;Lawlor, BA
通讯作者：
Lawlor, BA
DOI：
10.1111/j.1365-2788.1993.tb00582.x
发表时间：
1993-04-01
影响因子：
3.6
作者：
COLLACOTT, RA
通讯作者：
COLLACOTT, RA
影响因子：
29
作者：
Bejanin A;Iulita MF;Vilaplana E;Carmona-Iragui M;Benejam B;Videla L;Barroeta I;Fernandez S;Altuna M;Pegueroles J;Montal V;Valldeneu S;Giménez S;González-Ortiz S;Muñoz L;Padilla C;Aranha MR;Estellés T;Illán-Gala I;Belbin O;Camacho V;Wilson LR;Annus T;Osorio RS;Videla S;Lehmann S;Holland AJ;Zetterberg H;Blennow K;Alcolea D;Clarimon J;Zaman SH;Blesa R;Lleó A;Fortea J
通讯作者：
Fortea J