Right Anterior Temporal Degeneration, Emotions, and Loss of Nonverbal Semantics: The Emotional Semantic Variant Frontotemporal Dementia

Abstract

Anterior temporal lobe (ATL) degeneration is caused by a pathological process that has a focal onset in the left or right hemisphere. Patients with left-lateralized ATL atrophy typically meet criteria for semantic variant primary progressive aphasia (PPA), a clinical syndrome characterized by loss of verbal semantic knowledge. There is less consensus regarding the symptoms that emerge when atrophy targets the right ATL (rATL), but previous studies have emphasized prosopagnosia as well as alterations in emotion, memory, behavior, and semantic knowledge, symptoms that often lead to a diagnosis of behavioral variant frontotemporal dementia (bvFTD). The goal of the present study was to characterize the cognitive and socioemotional deficits of patients with rATL degeneration in order to refine current conceptualizations of the rATL clinical syndrome. We identified individuals clinically diagnosed as bvFTD or PPA in our cohort of patients prospectively evaluated for FTD-spectrum disorders. We selected patients who also underwent structural MRI and a comprehensive, multidisciplinary evaluation (n = 478). Based on structural MRI atrophy index, individuals with predominant, rATL atrophy (n = 46) were identified and patients with co-occurrence of significant frontal atrophy were excluded. Nineteen patients with rATL degeneration had undergone autopsy. We used the clinical histories to identify early symptoms and examined the cognitive, socioemotional, genetic, and pathological profiles of patients with rATL degeneration. In patients with rATL degeneration, the most common early clinical symptoms were loss of empathy (27%), person-specific semantic knowledge (23%), and complex compulsions (18%). On socioemotional testing and informant-reported measures, patients exhibited diminished interpersonal warmth, empathy, and emotional theory of mind. Neuropsychological testing revealed deficits in identifying famous people and discriminating facial affect despite preserved face perception. FTLD-TDP was the most frequent pathological correlate of rATL degeneration (84%), followed by Pick type (10%), a subtype of FTLD-tau. Our results indicate that patients with early, rATL-predominant degeneration present with a behavioral syndrome that results from loss of empathy for others. The underlying mechanism is a progressive loss of semantic knowledge for concepts of social-emotional relevance. We herein refer to this syndrome as emotional semantic variant frontotemporal dementia. We propose novel diagnostic criteria for this rATL syndrome in order to facilitate early identification in clinical and research settings. This classification is relevant because, if appropriately diagnosed, these patients most often have FTLD-TDP Type-C pathology.