Comparison of clinical characteristics between familial and non-familial early onset Alzheimer's disease
Comparison of clinical characteristics between familial and non-familial early onset Alzheimer's disease
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DOI：
10.1007/s00415-012-6481-y
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发表时间：
2012-10-01
影响因子：
6
通讯作者：
Mendez, Mario F.
中科院分区：
文献类型：
--
作者：
Joshi, Aditi;Ringman, John M.;Mendez, Mario F.
虽然家族性阿尔茨海默病（FAD）是一种早发性AD（EAD），但大多数EAD患者没有家族性疾病。最近的指南建议只在有两个一级亲属的EAD患者中检测引起FAD的基因。然而，一些FAD患者可能缺乏已知的家族史或其他怀疑FAD的指征，但仍然可能是FAD突变的携带者。该研究旨在确定区分FAD与非家族性EAD（NF-EAD）的临床特征。对32例PSEN 1相关AD患者和81例NF-EAD患者的大学队列进行了回顾性分析。与NF-EAD患者相比，PSEN 1患者的发病年龄更早（41.8 +/- A 5.2 vs. 55.9 +/- A 4.8岁），在初始评估时，病程较长（5.1 +/- A 3.4 vs. 3.3 +/- A 2.6年）和MMSE评分较低（10.74 +/- A 8.0 vs. 20.95 +/- A 5.8）。与FAD患者相比，NF-EAD患者更容易出现非记忆缺陷，特别是视觉空间症状。当年龄、病程和MMSE评分在逻辑回归模型中得到控制时，FAD患者比NF-EAD患者更可能有显著的头痛、肌阵挛、步态异常和假性延髓影响。除了更年轻的发病年龄外，PSEN 1突变的FAD患者与NF-EAD患者的不同之处在于头痛和假性延髓影响的病史，以及检查时的肌阵挛和步态异常。这些可能代表FAD和NF-EAD之间的病理生理学差异，在某些情况下，这些发现应导致遗传咨询和FAD基因检测的适当建议。
Although familial Alzheimer's disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 +/- A 5.2 vs. 55.9 +/- A 4.8 years) and, at initial assessment, a longer disease duration (5.1 +/- A 3.4 vs. 3.3 +/- A 2.6 years) and lower MMSE scores (10.74 +/- A 8.0 vs. 20.95 +/- A 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.