Focal anterior temporal lobe (ATL) degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant ATL (lATL) atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia (svPPA) and semantic dementia, patients with early right ATL (rATL) atrophy are more difficult to diagnose as their symptoms are less well understood. Focal rATL atrophy is associated with prominent emotional and behavioral changes, and patients often meet, or go on to meet, criteria for behavioral variant frontotemporal dementia (bvFTD). Uncertainty around early symptoms and absence of an overarching clinicoanatomical framework continue to hinder proper diagnosis and care of patients with rATL disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with rATL-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of bvFTD or svPPA and a structural MRI (n = 478). Based on neuroimaging criteria, we defined three patient groups: rATL-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the rATL (n = 79), and lATL-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic, and pathological profiles of these groups. In the rATL-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%), and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of famous people (from names and face), and facial affect naming (despite preserved face perception) than the frontal- and lATL-predominant groups. The clinical symptoms in the first three years of the disease alone were highly sensitive (81%) and specific (84%) differentiating rATL-predominant from frontal-predominant groups. FTLD-TDP (84%) was the most common pathology of the rATL-predominant group. rATL-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive decline in semantic memory for concepts of socioemotional relevance. Guided by our results, we outline new diagnostic criteria and propose the name, “semantic behavioral variant frontotemporal dementia” (sbvFTD), which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal rATL degeneration as well as in vivo prediction of FTLD-TDP pathology.

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