Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain.
Neurology. 2011 May 17;76(20):1720-5. doi: 10.1212/WNL.0b013e31821a44dd.
Early-onset Alzheimer disease (EOAD) diagnosis often represents a challenge because of the high frequency of atypical presentations. Our aim was to describe the clinical features, APOE genotype, and its pathologic correlations of neuropathologic confirmed EOAD.
Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD (<60 years).
Forty cases were selected. Mean age at onset was 54.5 years (range 46-60). The mean disease duration was 11 years with a mean diagnostic delay of 3.1 years. A total of 37.5% had a nonmemory presentation. Behavioral/executive dysfunction was the most prevalent atypical presentation. Incorrect initial clinical diagnoses were common (53%) in patients with atypical presentations, but rare when anterograde amnesia was the presenting symptom (4%). The incorrect initial clinical diagnoses were 2 behavioral variant frontotemporal lobar degeneration, 2 normal pressure hydrocephalus, 1 semantic dementia, 1 primary progressive aphasia, 1 corticobasal degeneration, 1 pseudodementia with depression, and 1 unclassifiable dementia. APOE genotype was ε3/ε3 in 59%, with no significant differences between typical and atypical presentations. APOE ε4 was 3.3 times more frequent in subjects with family history of AD. A total of 97.5% of the cases presented advanced neurofibrillary pathology. A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate.
One third of patients with pathologic confirmed EOAD presented with atypical symptoms. Patients with EOAD with nonamnestic presentations often receive incorrect clinical diagnoses.
早发性阿尔茨海默病（EOAD）的诊断常常具有挑战性，因为其表现形式常常不典型。本研究旨在描述经神经病理学证实的 EOAD 的临床特征、载脂蛋白 E（APOE）基因型及其与病理的相关性。
回顾性分析经神经病理学证实的 EOAD（<60 岁）患者的临床数据（发病年龄、家族史、临床表现、诊断延迟、诊断）和 APOE 基因型。
共纳入 40 例患者，发病年龄的平均值为 54.5 岁（范围 46-60 岁）。平均病程为 11 年，平均诊断延迟为 3.1 年。37.5%的患者以非记忆症状首发。行为/执行功能障碍是最常见的不典型表现。非典型表现患者的初始临床诊断错误较为常见（53%），而以顺行性遗忘为首发症状的患者则很少（4%）。初始临床诊断错误包括 2 例行为变异型额颞叶痴呆、2 例正常压力脑积水、1 例语义性痴呆、1 例原发性进行性失语、1 例皮质基底节变性、1 例抑郁性假性痴呆和 1 例无法分类的痴呆。APOE 基因型为 ε3/ε3 的占 59%，典型和非典型表现之间无显著差异。有 AD 家族史的患者 APOE ε4 发生频率高 3.3 倍。97.5%的病例存在高级别的神经纤维缠结病理。虽然大多数病例为局灶性，但共 45%的患者存在路易体病理，且与临床无显著相关性。
经神经病理学证实的 EOAD 患者中有 1/3 以不典型症状首发。EOAD 患者以非遗忘症状首发时，往往会得到错误的临床诊断。
