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Tracking progression in frontotemporal lobar degeneration

Serial MRI in semantic dementia

From the Dementia Research Centre, Department of Neurodegenerative Disease, Institute of Neurology, University College London, UK.

Address correspondence and reprint requests to Dr. Nick C. Fox, Dementia Research Centre, Institute of Neurology, Queen Square, London WC1N 3BG, UK nfox{at}dementia.ion.ucl.ac.uk

Background: Semantic dementia is a sporadic neurodegenerative disorder characterized by the progressive erosion of semantic processing and is one of the canonical subtypes of frontotemporal lobar degeneration. This study aimed to characterize the pattern of global and regional longitudinal brain atrophy in semantic dementia and to identify imaging biomarkers that could underpin therapeutic trials.

Methods: Twenty-one patients with semantic dementia (including eight pathologically confirmed cases) underwent whole-brain and region-of-interest analyses on volumetric brain MRI scans at two time points. Sample size estimates for trials were subsequently calculated using these data.

Results: Mean (SD) whole-brain atrophy rate was 39.6 (31.9) mL/y [3.2 (12.0) mL/y in controls], with ventricular enlargement of 8.9 (4.4) mL/y [1.0 (1.0) mL/y in controls]. All patients had a smaller left temporal lobe at baseline [left mean 31.9 (6.9) mL, right mean 49.2 (9.5) mL; p < 0.0001]; however, the mean rate of atrophy was significantly greater in the right temporal lobe [right 3.9 (1.7) mL/y, left 2.8 (1.2) mL/y; p = 0.02]. Similarly, whereas the left hippocampus was smaller at baseline, the mean atrophy rate was significantly greater in the right hippocampus. Using the atrophy rates generated, sample size requirements for clinical trials were found to be smallest for temporal lobe measurement.

Conclusions: These findings show that the rate of tissue loss in the right temporal lobe overtakes the left temporal lobe as semantic dementia evolves, consistent with the later development of symptoms attributable to right temporal lobe dysfunction. Furthermore, our findings demonstrate that MRI measures of temporal lobe volume loss could provide a feasible and sensitive index of disease progression in semantic dementia.

Abbreviations: BBSI = boundary shift integral–derived whole-brain volume change; BSI = boundary shift integral; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; MR = magnetic resonance; NT = not tested; PIQ = performance IQ; VIQ = verbal IQ.

Supplemental data at www.neurology.org

This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an Alzheimer's Research Trust Co-ordinating Centre. This work was also funded by the Medical Research Council UK. J.D.R. is supported by a Wellcome Trust Research Training Fellowship. J.D.W. is supported by a Wellcome Trust Intermediate Clinical Fellowship. N.C.F. holds an MRC Senior Clinical Fellowship. J.B. is supported by an Alzheimer's Research Trust fellowship.

Disclosure: The authors report no disclosures.

Received April 24, 2008. Accepted in final form July 22, 2008.