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

Rates of Hemispheric and Lobar Atrophy in the Language Variants of Frontotemporal Lobar Degeneration