Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).
Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).
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DOI：
10.1016/s1474-4422(16)30229-0
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发表时间：
2016-12
期刊：
影响因子：
48
通讯作者：
Bateman, Randall J.
中科院分区：
文献类型：
--
作者：
Tang, Mengxuan;Ryman, Davis C.;McDade, Eric;Jasielec, Mateusz S.;Buckles, Virginia D.;Cairns, Nigel J.;Fagan, Anne M.;Goate, Alison;Marcus, Daniel S.;Xiong, Chengjie;Allegri, Ricardo F.;Chhatwal, Jasmeer P.;Danek, Adrian;Farlow, Martin R.;Fox, Nick C.;Ghetti, Bernardino;Graff-Radford, Neill R.;Laske, Christopher;Martins, Ralph N.;Masters, Colin L.;Mayeux, Richard P.;Ringman, John M.;Rossor, Martin N.;Salloway, Stephen P.;Schofield, Peter R.;Morris, John C.;Bateman, Randall J.
在DIAN观察性研究（DIAN - obs）和已发表的文献中评估常染色体显性阿尔茨海默病（ADAD）非遗忘性神经症状的患病率。我们进行了分析，以阐明作为一个群体的ADAD突变携带者的神经学表现的患病率。使用DIAN-OBS研究数据库和189篇关于ADAD家族的同行评审出版物，我们提取了个体层面的数据，包括症状出现的年龄、从发病到死亡的病程，以及14项与ADAD相关的神经学发现，这些发现仅包括有症状的受试者。主要结果是各种神经症状的发生率以及年龄和特定突变对神经症状患病率的贡献。分析采用描述性统计、均值和频率比较以及多变量线性回归。我们的荟萃分析数据集包括1228名受影响的个体，其中753人有详细的临床描述。DIAN-OBS数据集包括107名具有详细临床数据的个体。DIAN患者最常见的非遗忘性认知表现为轻度-中度阿尔茨海默病的典型表现，包括视觉失认症（95% CI 45.7% - 64.6%）、失语（43.8% - 66.7%）和行为改变（51.5% - 70%）。从已发表的文献来看，视觉失认症的非遗忘认知表现的患病率为（95% CI 3.9% - 7.2%），失语症的患病率为（20%-26%），行为改变的患病率为（28.4% - 35.1%）。DIAN患者的非认知神经学表现患病率较低，包括肌阵挛和痉挛（3.8% - 15.0%）、癫痫发作（0.5% - 9.1%）和中度帕金森病（5.3% - 17.1%）。然而，在已发表的文献中，肌阵挛和痉挛的患病率为（95% CI 16.6% - 22.2%和12.5% - 17.6%），帕金森病的患病率为（10.1% - 15.0%），癫痫发作的患病率为（17.4% - 23.2%）。在两组中，发病年龄似乎影响了几种非认知表现的患病率，中风在发病年龄较大时更为普遍，运动症状在发病年龄较小和发病年龄较大时更为普遍。此外，症状总体上在疾病的后期临床阶段更为常见。将DIAN中非遗忘和非认知临床特征的患病率与已发表的文献进行比较，表明先前关于非认知特征的报道可能被高估了，而DIAN识别出除记忆障碍外更高的非遗忘认知症状。AD的非认知临床表现似乎只占轻中度ADAD的一小部分，除遗传状态外，还可能受疾病严重程度、环境和遗传因素的影响。本研究的结果阐明了ADAD的临床表现，包括年龄和疾病分期的影响。注意这些神经系统症状和筛查ADAD突变是必要的，如果存在。未来的工作需要确定导致这些神经症状的因素。
To evaluate the prevalence rates of non-amnestic neurological symptoms of autosomal dominant Alzheimer’s disease (ADAD) in the DIAN Observational Study (DIAN–OBS) and the published literature. Analyses were conducted to clarify the prevalence of neurological manifestations of ADAD mutation carriers as a group. Using the DIAN-OBS study database and 189 peer-reviewed publications on ADAD families, we extracted individual-level data on age of symptom onset, disease course from onset to death, and the presence of fourteen neurological findings that have been reported in association with ADAD and included symptomatic subjects only. The primary outcomes were the rates of various neurological symptoms and the contribution of age and specific mutations on the prevalence of the neurological symptoms. Analyses were done using descriptive statistics, comparisons of means and frequencies and multivariable linear regression. Our meta-analysis dataset includes 1228 affected individuals, with detailed clinical descriptions of 753. The DIAN–OBS dataset included 107 individuals with detailed clinical data. The most prevalent non-amnestic cognitive manifestations in DIAN were those typical of mild-moderate Alzheimer’s disease, including visual agnosia (95% CI 45·7%–64·6%), aphasia (43·8%–62·7%), and behavioral changes (51·5%–70·0%). The prevalence of non-amnestic cognitive manifestations from the published literature were (95% CI 3·9%–7·2%) for visual agnosia, (20%–26%) for aphasia, and (28·4%–35·1%) for behavioral changes. Prevalence of non-cognitive neurological manifestations in DIAN was low, including myoclonus and spasticity (3·8%–15·0%), seizures (0·5%–9·1%) and moderate for parkinsonism (5·3%–17·1%). Whereas, in the published literature the prevalence was (95% CI 16·6%–22·2% and 12·5%–17·6%) for myoclonus and spasticity, (10·1%–15·0%) for parkinsonism, and (17·4%–23·2%) for seizures. Age of onset appears to influence the prevalence of several non-cognitive manifestations in both groups, stroke being more prevalent at older ages of onset with motor symptoms being more prevalent at younger age of onset and at an older age of onset. Further, symptoms were overall more common in later clinical stages of disease. Comparing the prevalence of non-amnestic and non-cognitive clinical features in DIAN with the published literature indicates that previous reports of non-cognitive features are likely overestimated whereas DIAN identifies higher non-amnestic cognitive symptoms in addition to memory impairment. The non-cognitive clinical manifestations of AD appear to be in a minor fraction of mild-moderate ADAD and is likely influenced by disease severity, environmental and genetic factors in addition to genetic status. The results of this work clarify the clinical presentations of ADAD including the effects of age and disease stage. Attention to these neurologic symptoms and screening for ADAD mutations are warranted if present. Future work is needed to determine the factors which cause these neurologic symptoms.