Tracking progression with serial MRI in the language variants of frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder which presents with either behavioural or language impairment. The two language syndromes are known as progressive nonfluent aphasia (PNFA) and semantic dementia (SD). While cross-sectional imaging patterns of brain atrophy are well-described in FTLD there is little information about longitudinal imaging changes. Using volumetric methods including Freesurfer we measured longitudinal whole brain, hemispheric and lobar atrophy using serial MRI in a cohort of 18 patients with PNFA and 17 patients with SD as well as 14 cognitively-normal control subjects. We subsequently calculated sample size estimates for clinical trials. Whole brain atrophy rates were similar in PNFA and SD and significantly greater than controls. Rates of left hemisphere atrophy were greater than rates of right hemisphere atrophy in both PNFA and SD with no significant differences between the groups. The disease groups showed asymmetrical atrophy (more severe on the left) at baseline and hemispheric asymmetry significantly increased over time. Within a hemisphere, the fastest rate of atrophy varied between lobes: in SD temporal > frontal > parietal > occipital, whilst in PNFA frontal > temporal/parietal > occipital. In SD using temporal lobe measures of atrophy in clinical trials would provide the lowest sample sizes necessary whilst in PNFA left hemisphere atrophy measures provided the lowest sample size. These patterns of change provide information about disease evolution in the FTLD language variants that is of both clinical and neurobiological relevance.