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Abstract：
It is possible to calculate the number of years to the expected clinical onset (YECO) of autosomal-dominant Alzheimer\'s disease (adAD). A similar time scale is lacking for sporadic Alzheimer\'s disease (sAD). The purpose was to design and validate a time scale in YECO for patients with sAD in relation to CSF and PET biomarkers.
Patients diagnosed with Alzheimer\'s disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (Aβ42, total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, 11C-Pittsburgh compound B and 18F-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017).
The mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset).
A novel time scale in years of disease progression based on cognition was designed and validated in patients with AD using CSF and PET biomarkers. Two early- and late-disease onset subgroups were identified differing with respect to APOE e4.
Patients diagnosed with Alzheimer\'s disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (Aβ42, total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, 11C-Pittsburgh compound B and 18F-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017).
The mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset).
A novel time scale in years of disease progression based on cognition was designed and validated in patients with AD using CSF and PET biomarkers. Two early- and late-disease onset subgroups were identified differing with respect to APOE e4.
摘要：
背景：可以计算出常染色体显性遗传阿尔茨海默病（adAD）的预期临床发作（YECO）的年数。散发性阿尔茨海默病（sAD）缺乏类似的时间尺度。目的是设计和验证与CSF和PET生物标志物相关的sAD患者的YECO时间尺度。
方法：诊断为阿尔茨海默病的患者（AD，n=48）或轻度认知障碍（MCI，n=46）参与研究。他们在记忆诊所接受了标准化的临床检查，卡罗林斯卡大学医院,斯德哥尔摩,瑞典,包括现在和以前的病史，实验室筛选,认知评估，CSF生物标志物（Aβ42，总tau，和p-tau)，和大脑的核磁共振成像。还用两种PET示踪剂对它们进行了评估，11C-匹兹堡化合物B和18F-氟代脱氧葡萄糖。假设sAD和adAD的认知下降是一致的，这些患者的YECO是使用认知表现之间的关系方程计算的，YECO,和多年的教育(Almkvist等人。JIntNeuropsyolSoc23:195-203,2017)。
结果：sAD患者估计的临床发作后，疾病进展的平均当前点是3.2年，MCI患者估计的临床发作前是3.4年，五次认知测试的YECO中位数表明。YECO和生物标志物之间的关联是显著的，而实际年龄和生物标志物之间的差异无统计学意义。估计的疾病发作（实际年龄减去YECO）遵循双峰分布，在65岁之前（早期发作）和之后（晚期发作）具有最大频率。早期和晚期亚组在生物标志物和认知方面存在显著差异，但在控制YECO之后,除了APOEe4基因（早期比晚期更频繁）外，所有差异都消失了。
结论：在AD患者中使用CSF和PET生物标志物设计并验证了基于认知的疾病进展年的新时间尺度。在APOEe4方面，确定了两个早期和晚期疾病发作亚组。
方法：诊断为阿尔茨海默病的患者（AD，n=48）或轻度认知障碍（MCI，n=46）参与研究。他们在记忆诊所接受了标准化的临床检查，卡罗林斯卡大学医院,斯德哥尔摩,瑞典,包括现在和以前的病史，实验室筛选,认知评估，CSF生物标志物（Aβ42，总tau，和p-tau)，和大脑的核磁共振成像。还用两种PET示踪剂对它们进行了评估，11C-匹兹堡化合物B和18F-氟代脱氧葡萄糖。假设sAD和adAD的认知下降是一致的，这些患者的YECO是使用认知表现之间的关系方程计算的，YECO,和多年的教育(Almkvist等人。JIntNeuropsyolSoc23:195-203,2017)。
结果：sAD患者估计的临床发作后，疾病进展的平均当前点是3.2年，MCI患者估计的临床发作前是3.4年，五次认知测试的YECO中位数表明。YECO和生物标志物之间的关联是显著的，而实际年龄和生物标志物之间的差异无统计学意义。估计的疾病发作（实际年龄减去YECO）遵循双峰分布，在65岁之前（早期发作）和之后（晚期发作）具有最大频率。早期和晚期亚组在生物标志物和认知方面存在显著差异，但在控制YECO之后,除了APOEe4基因（早期比晚期更频繁）外，所有差异都消失了。
结论：在AD患者中使用CSF和PET生物标志物设计并验证了基于认知的疾病进展年的新时间尺度。在APOEe4方面，确定了两个早期和晚期疾病发作亚组。
