Measuring disease progression in frontotemporal lobar degeneration A clinical and MRI study

被引:62
作者
Gordon, E. [1 ]
Rohrer, J. D. [1 ]
Kim, L. G. [1 ]
Omar, R. [1 ]
Rossor, M. N. [1 ]
Fox, N. C. [1 ]
Warren, J. D. [1 ]
机构
[1] UCL, Inst Neurol, Dementia Res Ctr, London WC1N 3BG, England
基金
英国惠康基金;
关键词
SEMANTIC DEMENTIA; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; BEHAVIORAL VARIANT; CEREBRAL VOLUME; BRAIN; PHENOTYPE; CONSENSUS; ACCURATE; APHASIA;
D O I
10.1212/WNL.0b013e3181d1a879
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objectives: 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. Methods: 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. Results: Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p <= 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. Conclusions: 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. Neurology(R) 2010; 74: 666-673
引用
收藏
页码:666 / 673
页数:8
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