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Updated: Jun 16, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Measuring disease progression in frontotemporal lobar degeneration: a clinical and MRI study
E Gordon1, J D Rohrer, L G Kim
1Dementia Research Centre, Institute of Neurology, University College London, UK WC1N 3BG.
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 < 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.
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.
Insights
Objective MRI measures show disease progression in frontotemporal lobar degeneration (FTLD). Brain atrophy and ventricular expansion correlate with cognitive decline, aiding clinical trial design for FTLD subtypes.
Area of Science:
- Neuroscience
- Radiology
- Neurology
Background:
- Frontotemporal lobar degeneration (FTLD) is a group of progressive neurodegenerative disorders.
- Identifying reliable biomarkers for disease progression is crucial for therapeutic development.
Purpose of the Study:
- To evaluate magnetic resonance imaging (MRI) and behavioral measures for assessing disease progression in a longitudinal cohort of FTLD patients.
- To determine the utility of these biomarkers in stratifying FTLD subtypes for clinical trials.
Main Methods:
- A cohort of 32 FTLD patients (behavioral variant FTLD, semantic dementia, progressive nonfluent aphasia) and 24 controls underwent volumetric brain MRI and standard behavioral assessments at baseline and 1-year follow-up.
- Semi-automated image registration calculated annualized rates of brain atrophy (BBSI) and ventricular expansion (VBSI).
- Associations between MRI measures and changes in behavioral indices were analyzed.
Main Results:
- FTLD patients exhibited significantly greater rates of whole brain atrophy and ventricular expansion compared to controls.
- Changes in cognitive assessments (MMSE, FAB, CDR) correlated with MRI measures of progression, varying by FTLD subtype.
- MRI biomarkers (BBSI, VBSI) provided feasible sample size estimates for clinical trials, particularly for semantic dementia and progressive nonfluent aphasia subgroups.
Conclusions:
- Semi-automated MRI atrophy measures serve as valuable objective biomarkers for FTLD progression.
- Subtype stratification is essential for future clinical trials investigating disease-modifying therapies in FTLD.
- MRI biomarkers showed potential for detecting treatment effects, though sample sizes were larger for the behavioral variant FTLD subgroup and behavioral biomarkers generally.
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