PDF(Pubmed)
Abstract：
OBJECTIVE: Alzheimer\'s disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research.
METHODS: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests.
RESULTS: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD.
CONCLUSIONS: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.
METHODS: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests.
RESULTS: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD.
CONCLUSIONS: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.
摘要：
目的：阿尔茨海默病（AD）痴呆可能不是单一的疾病实体。早发性AD(EOAD)和晚发性AD(LOAD)一直统一在AD的同一缩写下，但是根据发病年龄解开异质性一直是AD研究领域的主要原则。
方法：99例AD患者（EOAD，n=54；负载，n=45）和66个认知正常对照完成了[18F]THK5351和[18F]氟美他莫（FLUTE）正电子发射断层扫描，以及结构磁共振成像和详细的神经心理学测试。
结果：EOAD患者的THK保留率较高，顶叶,和额叶，而LOAD患者在颞叶内侧的THK保留率较高。体素内相关分析显示，EOAD呈现局部FLUTE-THK相关的较窄区域，而LOAD表现出更广泛的相关性范围，延伸到整个顶侧-双侧-时间区域。EOAD患者的大脑区域较宽，皮质厚度与THK保留之间存在显着负相关，而在负载中，只有有限的脑区显示与THK滞留显著相关.在EOAD中,大多数认知测试结果与THK保留相关。然而,一些认知测试结果与LOAD中的THK保留相关。
结论：负载似乎显示tau和淀粉样蛋白逐渐增加，这两种病理是有关联的。另一方面,在EOAD中,tau和淀粉样蛋白可能更突然和独立地发展。这些发现表明LOAD和EOAD可能具有不同的病理机制过程。
方法：99例AD患者（EOAD，n=54；负载，n=45）和66个认知正常对照完成了[18F]THK5351和[18F]氟美他莫（FLUTE）正电子发射断层扫描，以及结构磁共振成像和详细的神经心理学测试。
结果：EOAD患者的THK保留率较高，顶叶,和额叶，而LOAD患者在颞叶内侧的THK保留率较高。体素内相关分析显示，EOAD呈现局部FLUTE-THK相关的较窄区域，而LOAD表现出更广泛的相关性范围，延伸到整个顶侧-双侧-时间区域。EOAD患者的大脑区域较宽，皮质厚度与THK保留之间存在显着负相关，而在负载中，只有有限的脑区显示与THK滞留显著相关.在EOAD中,大多数认知测试结果与THK保留相关。然而,一些认知测试结果与LOAD中的THK保留相关。
结论：负载似乎显示tau和淀粉样蛋白逐渐增加，这两种病理是有关联的。另一方面,在EOAD中,tau和淀粉样蛋白可能更突然和独立地发展。这些发现表明LOAD和EOAD可能具有不同的病理机制过程。
