Patterns of cortical thinning in the language variants of frontotemporal lobar degeneration

Abstract

Background: Frontotemporal lobar degeneration (FTLD) is a clinically, genetically, and pathologically heterogeneous neurodegenerative disorder. Two subtypes commonly present with a language disorder: semantic dementia (SemD) and progressive nonfluent aphasia (PNFA).

Methods: Patients meeting consensus criteria for PNFA and SemD who had volumetric MRI of sufficient quality to allow cortical thickness analysis were recruited from a tertiary referral clinic: 44 (11 pathologically confirmed) patients with SemD and 32 (4 pathologically confirmed) patients with PNFA and 29 age-matched and gender-matched healthy controls were recruited. Cortical thickness analysis was performed using the Freesurfer software tools.

Results: Patients with SemD had significant cortical thinning in the left temporal lobe, particularly temporal pole, entorhinal cortex, and parahippocampal, fusiform, and inferior temporal gyri. A similar but less extensive pattern of loss was seen in the right temporal lobe and (with increasing severity) also in left orbitofrontal, inferior frontal, insular, and cingulate cortices. Patients with PNFA had involvement particularly of the left superior temporal lobe, inferior frontal lobe, and insula, and (with increasing severity) other areas in the left frontal, lateral temporal, and anterior parietal lobes. Similar patterns were seen in the pathologically confirmed cases. Patterns of cortical thinning differed between groups: SemD had significantly more cortical thinning in the temporal lobes bilaterally while PNFA had significantly more thinning in the frontal and parietal lobes.

Conclusions: The language variants of frontotemporal lobar degeneration have distinctive and significantly different patterns of cortical thinning. Increasing disease severity is associated with spread of cortical thinning and the pattern of spread is consistent with progression of clinical deficits.

Figure 1 Pattern of significantly thinner cortex in patients with (A) semantic dementia and (B) progressive nonfluent aphasia compared to controls Colored bar represents False Discovery Rate-corrected p values.

Figure 2 Pattern of significantly thinner cortex in (A) pathologically confirmed semantic dementia and (B) pathologically confirmed progressive nonfluent aphasia (represented on an averaged brain, top, and an inflated cortical map, bottom) compared to controls Colored bar represents False Discovery Rate-corrected p values.

Figure 3 Percentage cortical thickness difference from controls in semantic dementia in groups 1, 2, 3 and the total group Only lateral views are shown. Colored bar represents percentage thickness difference. Areas of thinning seen in the medial views (not shown) were as follows: group 1, left hemisphere (LH) temporal lobe (anterior > posterior), right hemisphere (RH) anterior temporal lobe; group 2, LH temporal lobe (anterior > posterior), cingulate (anterior > posterior), RH temporal lobe (anterior > posterior); group 3, LH temporal lobe (anterior > posterior), cingulate (anterior > posterior), orbitofrontal lobe, superior frontal lobe, RH temporal lobe (anterior > posterior), anterior cingulate.

Figure 4 Percentage cortical thickness difference from controls in progressive nonfluent aphasia in groups 1, 2, 3 and the total group Only lateral views are shown. Colored bar represents percentage thickness difference. Areas of thinning seen in the medial views (not shown) were as follows: group 1, left hemisphere (LH) superior frontal lobe; group 2, LH superior frontal lobe; group 3, LH superior frontal, cingulate, temporal lobe (anterior > posterior), right hemisphere (RH) posterior cingulate, anterior temporal.