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NEUROLOGY 2009;72:1843-1849
© 2009 American Academy of Neurology

Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year

D. S. Knopman, MD, C. R. Jack, Jr, MD, J. H. Kramer, PsyD, B. F. Boeve, MD, R. J. Caselli, MD, N. R. Graff-Radford, MBBCh, M. F. Mendez, MD, PhD, B. L. Miller, MD and N. D. Mercaldo, MS

From the Mayo Clinic (D.S.K., C.R.J., B.F.B.), Rochester, MN; University of California (J.H.K.), San Francisco, CA; Mayo Clinic (R.J.C.), Scottsdale, AZ; Mayo Clinic (N.R.G.-R.), Jacksonville, FL; University of California (M.F.M.), Los Angeles, CA; University of California (B.L.M.), San Francisco, CA; and National Alzheimer's Coordinating Center (N.D.M.), Seattle, WA.

Address correspondence and reprint requests to Dr. David Knopman, Department of Neurology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester MN 55905 knopman{at}mayo.edu

Background: Measurement of volumetric changes with MR might be a useful surrogate endpoint for clinical trials in frontotemporal lobar degeneration (FTLD). Because there is only limited longitudinal imaging data currently available, we measured the rate of change over 1 year of whole brain volume (WBV) and ventricular volume (VV) in patients with FTLD.

Methods: Subjects with an FTLD cognitive syndrome were recruited from five centers using standard clinical diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), semantic dementia (SMD), and progressive logopenic aphasia. Structural brain imaging, using three-dimensional T1-weighted sequences at 1.5 teslas, and cognitive, behavioral, and functional assessments were performed at baseline and approximately 1 year later. The boundary shift integral algorithm was used to determine change in WBV and VV.

Results: There were 76 patients (mean age 64 years; 41 men and 35 women) who had usable baseline and annual scans. The group-wise annualized change was –1.62% (SD 1.03, range +0.69 to –3.6) for WBV and 11.6% (SD 5.9, range –1.3 to 23.9) for VV. Rates of change were similar among bvFTD, PNFA, and SMD groups. Longitudinal changes in WBV and VV were correlated with decline on clinical global and cognitive measures.

Conclusions: Multicenter, serial measurements of whole brain volume (WBV) and ventricular volume (VV) from magnetic resonance scans were feasible in patients with frontotemporal lobar degeneration (FTLD). Using WBV or VV as outcome measures would require recruiting (at 80% power) 139 or 55 subjects per group to detect a small (25%) or medium-sized (40%) effect in a randomized, placebo-controlled trial of a putative agent for FTLD.

Abbreviations: AD = Alzheimer disease; BSI = boundary shift integral; bvFTD = behavioral variant frontotemporal dementia; CBD = corticobasal degeneration; CI = confidence interval; FTLD = frontotemporal lobar degeneration; FTLD-CDR = frontotemporal lobar degeneration modified Clinical Dementia Rating Scale; MMSE = Mini-Mental State Examination; MR = magnetic resonance; NS = not significant; PLA = progressive logopenic aphasia; PNFA = progressive nonfluent aphasia; PSP = progressive supranuclear palsy; SMD = semantic dementia; TIV = total intracranial volume; VV = ventricular volume; WBV = whole brain volume.

Supplemental data at www.neurology.org

Supported by National Institute on Aging studies R01-AG023195, R01-AG11378, P50-AG 16574 (Mayo Alzheimer's Disease Research Center), P30-AG19610 (Arizona Alzheimer Disease Center), P50-AG016570 (UCLA Alzheimer Disease Research Center), P50-AG023501 (UCSF Alzheimer Disease Research Center), and U01 AG016976 (National Alzheimer's Coordinating Center).

Disclosures: Author disclosures are provided at the end of the article.

Portions of this work were presented at the American Academy of Neurology, Chicago, IL, April 23, 2008.

Received December 8, 2008. Accepted in final form February 20, 2009.




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