AbstractBackgroundPatients with Primary Progressive Aphasia (PPA) have a prominent, isolated language deficit during the initial phase of the illness, with other cognitive and affective functions being affected later on (Gorno‐Tempini et al. 2011; Mesulam, 2001). Based on evidence that executive, memory and socioaffective functions are associated with functional independence (De Paula et al. 2015), we hypothesized that greater atrophy in cognitive or affective brain networks outside language networks is predictive of dementia in PPA. The development of quantitative neuroanatomical prognostic biomarkers for loss of independent functioning would be valuable in research and clinically (e.g. treatment recommendations, family education).Method50 PPA patients (17 agrammatic, 14 semantic, and 19 logopenic variant), who underwent a clinical and MRI evaluation at baseline and had at least 6 months of follow‐up, were selected. For each patient we measured the time between the first visit and the progression to dementia or last observation. We estimated individual network atrophy using surface‐based analyses described in our previous studies and using large‐scale cortical cognitive and affective networks derived from the Yeo et al. 2011 parcellation. We performed Cox regression models to test the hypothesis that greater baseline atrophy in cortical networks subserving non‐language cognitive or affective functions predicts time to dementia, but that greater atrophy in the visual association network (serving as a control) does not.ResultUnivariate Cox regression analysis showed that patients with greater atrophy outside the language network, in left hemisphere heteromodal association and paralimbic areas, including the default mode, frontoparietal, salience and ventral frontotemporal networks, had the highest risk of progression to dementia within a shorter time period of time (HR: 2.26, 95% CI: 1.45‐ 3.51). Atrophy in the language network was also a predictor, although slightly weaker (HR: 2.05, 95% CI: 1.41‐ 2.98). Atrophy in the visual association network did not predict time of conversion to dementia (left hemisphere: HR: 1.19, 95% CI: 0.86‐ 1.64; right hemisphere: HR: 1.21, 95% CI: 0.86‐ 1.68).ConclusionIn PPA patients, baseline cortical atrophy outside language networks is an important predictor of more rapid progression to dementia. This measure should be included in precision medicine models of prognosis in PPA.