Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
J Neurosci. 2012 Nov 14;32(46):16233-42. doi: 10.1523/JNEUROSCI.2462-12.2012.
Amyloid burden and white matter hyperintensities (WMH) are two common markers of neurodegeneration present in advanced aging. Each represents a potential early indicator of an age-related neurological disorder that impacts cognition. The presence of amyloid is observed in a substantial subset of cognitively normal older adults, but the literature remains equivocal regarding whether amyloid in nondemented populations is deleterious to cognition. Similarly, WMH are detected in many nondemented older adults and there is a body of evidence indicating that WMH are associated with decreased executive function and other cognitive domains. The current study investigated amyloid burden and WMH in clinically normal older adult humans aged 65-86 (N = 168) and examined each biomarker's relation with cognitive domains of episodic memory, executive function, and speed of processing. Factors for each domain were derived from a neuropsychological battery on a theoretical basis without reference to the relation between cognition and the biomarkers. Amyloid burden and WMH were not correlated with one another. Age was associated with lower performance in all cognitive domains, while higher estimated verbal intelligence was associated with higher performance in all domains. Hypothesis-driven tests revealed that amyloid burden and WMH had distinct cognitive profiles, with amyloid burden having a specific influence on episodic memory and WMH primarily associated with executive function but having broad (but lesser) effects on the other domains. These findings suggest that even before clinical impairment, amyloid burden and WMH likely represent neuropathological cascades with distinct etiologies and dissociable influences on cognition.
淀粉样蛋白负担和脑白质高信号（WMH）是两种常见的神经退行性变标志物，存在于衰老后期。每一种都代表了一种与年龄相关的神经障碍的潜在早期指标，这种障碍会影响认知。在认知正常的老年人群中，大量亚组存在淀粉样蛋白，但文献对于无痴呆人群中的淀粉样蛋白是否对认知有害仍然存在争议。同样，WMH 在许多无痴呆的老年人群中被检测到，有大量证据表明 WMH 与执行功能和其他认知领域的下降有关。本研究调查了 65-86 岁临床正常的老年人类的淀粉样蛋白负担和 WMH，并检查了每个生物标志物与情景记忆、执行功能和处理速度等认知领域的关系。每个领域的因素都是基于理论从神经心理学测试中得出的，而不参考认知与生物标志物之间的关系。淀粉样蛋白负担和 WMH 彼此之间没有相关性。年龄与所有认知领域的表现下降有关，而较高的估计言语智力与所有领域的较高表现有关。基于假设的测试表明，淀粉样蛋白负担和 WMH 具有不同的认知特征，淀粉样蛋白负担对情景记忆有特定影响，而 WMH 主要与执行功能有关，但对其他领域也有广泛（但较小）的影响。这些发现表明，即使在出现临床损伤之前，淀粉样蛋白负担和 WMH 可能代表具有不同病因和对认知有不同影响的神经病理级联反应。
