Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI

Alzheimer's disease (AD) is characterized by progressive cerebral atrophy, which may be assessed by using volumetric MRI. We describe a voxel-based analysis of nonlinear-registered serial MRI to demonstrate the most statistically significant (P < 0.001) regions of change at different stages of the disease. We compared presymptomatic (n = 4), mild (n = 10), and moderately affected (n = 12) patients with early- and late-onset AD, with age- and sex-matched controls, and demonstrated increasing global atrophy with advancing disease. Significantly increased rates of hippocampal atrophy were seen in presymptomatic and mildly affected patients. There was a shift in the distribution of temporal lobe atrophy with advancing disease; the inferolateral regions of the temporal lobes showed the most significantly increased rates of atrophy by the time the patients were mildly or moderately affected. Significantly increased rates of medial parietal lobe atrophy were seen at all stages, with frontal lobe involvement occurring later in the disease. Our results suggest that the sites showing the most significant rates of atrophy alter as the disease advances, and that regional atrophy is already occurring before the onset of symptoms. This technique provides insights into the natural history of AD, and may be a valuable tool in assessing the efficacy of disease-modifying treatments, especially if these treatments were to have region-specific effects.

阿尔茨海默病（Alzheimer's disease, AD）以进行性脑萎缩为特征，可通过容积磁共振成像（volumetric MRI）进行评估。本研究采用基于体素的分析方法，对非线性配准的系列磁共振成像数据进行处理，以明确该病不同病程阶段中具有统计学显著性差异（P < 0.001）的脑萎缩变化区域。本研究对比了4例症状前期、10例轻度、12例中度AD患者，以及早发性与晚发性AD患者，并设置年龄与性别匹配的健康对照组，结果显示随着疾病进展，全脑萎缩程度逐渐加重。症状前期及轻度患病患者的海马体萎缩速率显著升高。随着疾病进展，颞叶萎缩的分布模式发生改变：当患者处于轻度或中度患病阶段时，颞叶下外侧区域的萎缩速率升高最为显著。全病程阶段均可见内侧顶叶萎缩速率显著升高，而额叶受累则出现在疾病后期。本研究结果表明，萎缩速率最显著的脑区会随疾病进展发生动态变化，且脑区局部萎缩早在症状出现前就已发生。该技术可为AD的自然病程研究提供新视角，同时有望成为评估疾病修饰治疗疗效的有效工具，尤其当此类治疗具有脑区特异性作用时。