Dementia Research Centre, UCL Institute of Neurology, University College London, London, United Kingdom.
Ann Neurol. 2015 Jan;77(1):33-46. doi: 10.1002/ana.24296. Epub 2014 Nov 17.
Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).
Twenty-three patients with bvFTD (12 having genetic mutations), and 18 age-matched control participants were assessed using DTI and neuropsychological batteries at baseline and ~1.3 years later. Baseline and follow-up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated.
In the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: -6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: -7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: -6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: -6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change.
Serial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials.
需要新的生物标志物来监测神经退行性疾病的进展。使用弥散张量成像（DTI）测量白质（WM）的微观结构变化可能是一种有用的结果测量方法。在这里，我们报告了使用行为变异额颞叶痴呆（bvFTD）队列的连续 DTI 测量的 WM 变化轨迹。
23 名 bvFTD 患者（12 名携带基因突变）和 18 名年龄匹配的对照组参与者在基线和大约 1.3 年后使用 DTI 和神经心理学测试进行评估。使用基于群组的方法对基线和随访 DTI 扫描进行配准。计算 DTI 指标、神经心理学测量和全脑体积的年变化率。比较 DTI 指标的性能，并计算潜在临床试验的样本量。
在整个 bvFTD 组中，右侧胼胝体扣带束的各向异性分数（FA）和平均弥散度（MD）的变化率最大（FA：-6.8%/年，p<0.001；MD：2.9%/年，p=0.01）。MAPT 携带者在左侧钩束内的变化最大（FA：-7.9%/年，p<0.001；MD：10.9%/年，p<0.001）；散发性 bvFTD 和 C9ORF72 携带者在右侧胼胝体扣带束内的变化最大（散发性 bvFTD，FA：-6.7%/年，p<0.001；MD：3.8%/年，p=0.01；C9ORF72，FA：-6.8%/年，p=0.004）。使用 FA 变化进行样本量估计的数值明显低于神经心理学或全脑测量的变化。
连续 DTI 扫描可能有助于测量 bvFTD 的疾病进展，出现特定的 WM 损伤轨迹。样本量计算表明，纵向 DTI 可能是未来临床试验中的一种有用的生物标志物。
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