Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year.
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.
Knopman
D S
DS
Department of Neurology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA. knopman@mayo.edu
Jack
C R
CR
Kramer
J H
JH
Boeve
B F
BF
Caselli
R J
RJ
Graff-Radford
N R
NR
Mendez
M F
MF
Miller
B L
BL
Mercaldo
N D
ND
D000368:Aged; D000465:Algorithms; D001037:Aphasia / Q000473:pathology; D018888:Aphasia, Primary Progressive / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology*; D002986:Clinical Trials as Topic; D003704:Dementia / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012720:Severity of Illness Index