Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK.
Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK.
Neuroimage. 2021 Sep;238:118214. doi: 10.1016/j.neuroimage.2021.118214. Epub 2021 Jun 9.
A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.
更好地理解阿尔茨海默病（AD）等疾病导致独立性丧失之前的早期大脑变化，对于开发疾病修饰疗法至关重要。定量 MRI，如 T2 弛豫测量，可以识别与病理学早期阶段相关的微观结构变化。最近的证据表明，T2 异质性可能是一种比绝对 T2 更能反映早期病理学的更有信息的 MRI 测量指标。在这里，我们测试了脑完整性的 T2 标志物是否先于我们已知存在于已确立的 AD 中的体积变化，以及这些变化是否在 MTL 亚区中最为明显，这些亚区在 AD 早期受到的影响最大。我们发现，与健康的老年对照组（n=99）相比，轻度认知障碍（MCI；n=49）患者的所有 MTL 亚区的 T2 异质性都更大，但这种增加在 MTL 皮质中最大，在齿状回中最小。这反映了 AD 中神经退行性变的时空进展。CA1-3 和内嗅皮层的 T2 异质性和内嗅皮层的体积显示出一些预测认知下降的能力，而绝对 T2 则不能，但需要进一步的研究来验证这一结果。MTL 皮质中 T2 异质性的增加可能反映了局部的病理变化，并且可能是萎缩之前最早可检测到的大脑变化之一。最后，我们描述了一种机制，通过该机制，通过配对联想学习任务的准确性和反应时间来衡量的记忆会随着年龄的增长而恶化。年龄相关的记忆缺陷部分归因于亚区体积较小，而亚区体积又与 T2 异质性的增加直接相关。我们提出，T2 异质性高的组织代表了存在永久性损伤风险但具有治疗潜力的组织。这对神经退行性疾病的早期检测和脑-行为关系的研究具有重要意义。
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