White matter imaging contributes to the multimodal diagnosis of frontotemporal lobar degeneration

Abstract

Objective: To evaluate the distribution of white matter (WM) disease in frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to evaluate the relative usefulness of WM and gray matter (GM) for distinguishing these conditions in vivo.Methods: Patients were classified as having FTLD (n ϭ 50) or AD (n ϭ 42) using autopsy-validated CSF values of total-tau:␤-amyloid (t-tau:A␤ 1-42 ) ratios. Patients underwent WM diffusion tensor imaging (DTI) and volumetric MRI of GM. We employed tract-specific analyses of WM fractional anisotropy (FA) and whole-brain GM density analyses. Individual patient classification was performed using receiver operator characteristic (ROC) curves with FA, GM, and a combination of the 2 modalities.Results: Regional FA and GM were significantly reduced in FTLD and AD relative to healthy seniors. Direct comparisons revealed significantly reduced FA in the corpus callosum in FTLD relative to AD. GM analyses revealed reductions in anterior temporal cortex for FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to FTLD. ROC curves revealed that a multimodal combination of WM and GM provide optimal classification (area under the curve ϭ 0.938), with 87% sensitivity and 83% specificity. Conclusions: FTLD and AD have significant WM and GM defects. A combination of DTI and volumetric MRI modalities provides a quantitative method for distinguishing FTLD and AD in vivo.Neurology ® 2012;78:1761-1768 GLOSSARY A␤ 1-42 ϭ ␤-amyloid; AD ϭ Alzheimer disease; CC ϭ corpus callosum; CST ϭ corticospinal tract; DTI ϭ diffusion tensor imaging; DWI ϭ diffusion-weighted image; FA ϭ fractional anisotropy; FDR ϭ false discovery rate; FTLD ϭ frontotemporal lobar degeneration; GM ϭ gray matter; IFO ϭ inferior fronto-occipital; ILF ϭ inferior longitudinal fasciculus; MMSE ϭ MiniMental State Examination; MPRAGE ϭ magnetization-prepared rapid gradient echo; PBAC ϭ Philadelphia Brief Assessment of Cognition; ROC ϭ receiver operator characteristic; SLF ϭ superior longitudinal fasciculus; t-tau ϭ total-tau; TSA ϭ tractspecific analysis; UNC ϭ uncinate fasciculus; WM ϭ white matter.

Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia

“…These areas are implicated in both FTLDtau and FTLD-TDP. 22,32,35,36 We previously found that lower copy numbers of rs1768208 MOBP risk allele are associated with reduced FA in SLF in a clinically mixed cohort; however, this was in a more posterior and superior region than in the current study of sporadic bvFTD. 11 Additional work is needed to further investigate these imaging findings.…”

Multimodal imaging evidence of pathology-mediated disease distribution in corticobasal syndrome

“…These studies suggested that on average there is reduced FA in the anterior corpus callosum of FTLD and reduced GM in the precuneus and posterior cingulate of AD. 7,8 While the neuroanatomic distribution of disease that contributed to classification in prior studies could be confounded by the clinical heterogeneity of the samples, the current study observed similar regions contributing to pathologic heterogeneity in a single clinical syndrome. Specifically, anterior corpus callosum WM and precuneus and posterior cingulate GM appear also to differentiate CBS-non-AD and CBS-AD.…”

“…Our findings also converge with 2 studies suggesting that reduced WM integrity in the corpus callosum is associated with CBS 21 and is sensitive and specific for detecting FTLD relative to AD pathology. 7,8 In one prior neuroimaging report of autopsy-confirmed corticobasal degeneration, GM disease was seen in posterior and superior frontal, insula, and supplementary motor regions, and WM disease was seen in the corpus callosum and external capsule. 22 While this study used both GM and WM imaging, this work differs from ours by assessing volumetric measures of WM rather than DTI.…”

“…2,5,6 Multimodal neuroimaging studies suggest that AD and FTLD can be dissociated on the basis of gray matter (GM) and white matter (WM) neuroimaging. 7,8 Specifically, GM atrophy was evident in both AD and FTLD in T1-weighted MRI studies, but diffusion tensor imaging (DTI) revealed more WM disease in FTLD than in AD. Additional neuroimaging evidence suggests that tau pathology, the most common form of underlying pathology in CBS, is associated with substantial WM imaging changes 9 and that these findings converge with neuropathologic evidence of WM disease burden in 4-repeat tauopathy.…”

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

“…Six studies performed whole brain analysis , McMillan, Brun et al 2012, Pettit, Bastin et al 2012, Prudlo, Bissbort et al 2012, Sarica, Cerasa et al 2014. Whole brain TBSS found significant changes in FA and MD in the SLF bilaterally (Sarica, Cerasa et al 2014.…”