Right temporal degeneration and socioemotional semantics: semantic behavioural variant frontotemporal dementia

Abstract

Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-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 right anterior temporal lobe-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 faces) and facial affect naming (despite preserved face perception) than the frontal- and left-predominant anterior temporal lobe-predominant groups. The clinical symptoms in the first 3 years of the disease alone were highly sensitive (81%) and specific (84%) differentiating right anterior temporal lobe-predominant from frontal-predominant groups. Frontotemporal lobar degeneration-transactive response DNA binding protein (84%) was the most common pathology of the right anterior temporal lobe-predominant group. Right anterior temporal lobe-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 behavioural variant frontotemporal dementia', which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal right anterior temporal lobe degeneration as well as in vivo prediction of frontotemporal lobar degeneration-transactive response DNA binding protein pathology.

Keywords: FTLD-TDP type C; frontotemporal dementia; loss of empathy and non-verbal semantics; person-specific knowledge; right temporal lobe-predominant neurodegeneration.

Figure 1

Patient selection. We searched the UCSF MAC database. The first inclusion criterion was the clinical diagnosis; we included all participants who received a clinical diagnosis of bvFTD or svPPA. We then excluded all patients who did not have a brain MRI within 1 year of the first research evaluation. Next, we included participants who had peak atrophy in either the right temporal lobe, frontal lobe or left temporal lobe on a brain MRI W-score map and showed predominant atrophy in their respective lobe based on an atrophy index. Posterior = parietal or occipital lobes.

Figure 2

Neuroimaging in right temporal-, left temporal- and frontal-predominant neurodegeneration and chronology of symptoms. (A) Lateral and mesial views. Predominant right temporal, left temporal or frontal atrophy was used as part of the inclusion criteria based on a data-driven neuroimaging approach. The right temporal-predominant group exhibited maximum atrophy in the right temporal lobe more than the left ATL with involvement of the right more than left insula, right caudate and right more than left subgenual anterior cingulate cortex. Notably, there is sparing of the frontal, parietal and occipital lobes. The left temporal-predominant group shows maximum atrophy in the left temporal lobe more than the right ATL with involvement of the left more than right insula, left caudate and left subgenual anterior cingulate cortex. Further, there is sparing of the frontal, parietal and occipital lobes. The frontal group shows bilateral lateral and mesial frontal and left temporal volume loss but relative sparing of the right temporal lobe. (B) Top left: The symptom legend. Top right: Panel shows the symptoms chronology in the right temporal-predominant group; the most common early symptoms in this group are loss of empathy, loss of person-specific knowledge and rigid thought process and complex compulsion. Bottom left: Panel shows symptom chronology in the frontal-predominant group; the most common early symptoms in this group are lack of judgement and dysexecutive symptoms, apathy and disinhibition. The right lower corner shows symptom chronology in the left temporal-predominant group; the most common early symptoms in this group are verbal semantic loss, loss of person-specific knowledge and rigid thought process and complex compulsion.

Figure 3

Socioemotional and neuropsychological characteristics. The figure shows the results of the main socioemotional tests that can help distinguish right temporal- from frontal-predominant patients. More details can be found in Table 2. Although all disease groups had difficulties with Famous Faces Naming, only right temporal and a lesser degree left temporal-predominant patients, had difficulties on Famous Face Recognition and Semantic Association. Although all disease groups showed impaired simple and complex social cues recognition on the TASIT–EET and TASIT-Sarcasm, only the frontal-predominant group showed impairment on the control cognitive task, TASIT-Sincere. Right temporal-predominant patients showed significantly worse performance on the complex social cue, TASIT-Sarcasm, compared to the frontal-predominant group. The right temporal-predominant group showed increased coldness compared to the frontal-predominant group. The right and left temporal-predominant groups had difficulty with the Emotional Theory of Mind but not with the Cognitive Theory of Mind task, in contrast to the frontal-predominant group that demonstrated impairment in both Cognitive and Emotional Theory of Mind.

Figure 4

Clinico-anatomical model. Schematic representation of the clinical symptom overlap in FTD between sbvFTD and svPPA (both under the semantic dementia spectrum and often have FTLD-TDP-C pathology) and bvFTD.