Dementia Research Centre, Institute of Neurology, University College London, UK WC1N 3BG.
Neurology. 2010 Feb 23;74(8):666-73. doi: 10.1212/WNL.0b013e3181d1a879.
There is currently much interest in biomarkers of disease activity in frontotemporal lobar degeneration (FTLD). We assessed MRI and behavioral measures of progression in a longitudinal FTLD cohort.
Thirty-two patients with FTLD (11 behavioral variant frontotemporal dementia [bvFTD], 11 semantic dementia [SemD], 10 progressive nonfluent aphasia [PNFA]) and 24 age-matched healthy controls were assessed using volumetric brain MRI and standard behavioral measures (Mini-Mental State Examination, Frontal Assessment Battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory with Caregiver Distress scale) at baseline and 1 year later. A semi-automated image registration protocol was used to calculate annualized rates of brain atrophy (brain boundary shift integral [BBSI]) and ventricular expansion (ventricular boundary shift integral [VBSI]). Associations between these rates and changes in behavioral indices were investigated.
Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p < or = 0.004). Rates of ventricular expansion were greater in the entire cohort (p < 0.001) and the SemD (p = 0.002) and PNFA (p = 0.05) subgroups compared with controls. Changes in Mini-Mental State Examination, Frontal Assessment Battery, and Clinical Dementia Rating Scale scores were associated with MRI measures of progression, though not uniformly across FTLD subgroups. Both BBSI and VBSI yielded feasible sample size estimates for detecting meaningful treatment effects in SemD and PNFA language subgroups. Sample sizes were substantially larger using MRI biomarkers for the bvFTD subgroup, and using behavioral biomarkers in general.
Semi-automated MRI atrophy measures are potentially useful objective biomarkers of progression in frontotemporal lobar degeneration (FTLD); however, careful stratification of FTLD subtypes will be important in future clinical trials of disease-modifying therapies.
目前人们对额颞叶变性（FTLD）的疾病活动生物标志物很感兴趣。我们评估了纵向 FTLD 队列中 MRI 和行为进展的测量结果。
32 例 FTLD 患者（11 例行为变异型额颞叶痴呆[bvFTD]、11 例语义性痴呆[SemD]、10 例进行性非流利性失语症[PNFA]）和 24 名年龄匹配的健康对照者在基线和 1 年后分别使用容积脑 MRI 和标准行为测量（简易精神状态检查、额叶评估量表、临床痴呆评定量表、神经精神问卷伴照料者负担量表）进行评估。采用半自动图像配准方案计算脑萎缩的年增长率（脑边界移位积分[BBSI]）和脑室扩张的年增长率（脑室边界移位积分[VBSI]）。研究了这些比率与行为指标变化之间的相关性。
整个 FTLD 队列和各亚组的全脑萎缩率均大于对照组（均 p<0.004）。整个队列（p<0.001）和 SemD（p=0.002）和 PNFA（p=0.05）亚组的脑室扩张率大于对照组。简易精神状态检查、额叶评估量表和临床痴呆评定量表评分的变化与 MRI 进展测量值相关，但 FTLD 亚组之间并不一致。BBSI 和 VBSI 都能为 SemD 和 PNFA 语言亚组检测有意义的治疗效果提供可行的样本量估计。使用 MRI 生物标志物时，bvFTD 亚组的样本量要大得多，一般使用行为生物标志物时也是如此。
半自动化 MRI 萎缩测量可能是额颞叶变性（FTLD）进展的有用客观生物标志物；然而，在未来针对疾病修饰疗法的临床试验中，对 FTLD 亚型进行仔细分层将非常重要。
