An update on semantic dementia: genetics, imaging, and pathology

Abstract

Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD. Task-related fMRI have also demonstrated the relative preservation of frontal and parietal regions alongside preserved memory performance. In addition, recent longitudinal studies have demonstrated that, with disease progression, atrophy encroaches into the contralateral temporal pole and medial prefrontal cortices, which reflects emerging changes in behaviour and social cognition. Notably, unlike other frontotemporal dementia subtypes, recent research has demonstrated strong clinicopathological concordance in SD, with TDP43 type C as the most common pathological subtype. Moreover, an underlying genetic cause appears to be relatively rare in SD, with the majority of cases having a sporadic form of the disease. The relatively clear diagnosis, clinical course, and pathological homogeneity of SD make this syndrome a promising target for novel disease-modifying interventions. The development of neuroimaging markers of disease progression at the individual level is an important area of research for future studies to address, in order to assist with this endeavour.

Early-stage right temporal lobe variant of frontotemporal dementia: 3 years of follow-up observations

“…This symptom may be associated with hypoperfusion in the right fusiform gyrus, which is considered to play a key role in facial recognition 13. Word-finding difficulty and semantic aphasia may be associated with hypoperfusion in the left temporal and frontal lobes, as well as cases in SD3 These findings suggested that his symptoms, as the disease progressed, depended on which brain regions were affected by hypoperfusion. Importantly, he initially presented with only self-centred behaviour and a lack of empathy.…”

Novel Alzheimer’s disease subtypes identified using a data and knowledge driven strategy

“…Participnats in the Uncompensated MCI cluster presented an uncommon pattern of brain atrophy; the hippocampal area was relatively preserved in observed median volume compared to the Anosognosia Dementia and Insightful Dementia subtypes. Left hemisphere dominance in the atrophied regions could reflect the relation to language and semantic brain areas [32][33][34][35] . The clinical finding is supported by the Left hemisphere Cingulum, Frontal inferior operculum, Fusiform 36 Superior Parietal and Putamen had significantly more reduced volume in Uncompensated MCI compared to Affective MCI.…”

Topographic Markers Drive Proteinopathies to Selection of Target Brain Areas at Onset in Neurodegenerative Dementias

“…However, accuracy and consistency of targeting are valid also for the atypical syndromes of AD. Another type of phenotypic diversity is that some dementias may strike a brain area on the left hemisphere in a first patient and at the same time, the homolog brain area on the right hemisphere in a second patient (e.g., the left/right temporal variant FTD; Kumfor et al, 2016 ; Landin-Romero et al, 2016 ). Clinicoanatomical convergence refers to the fact that degeneration sometimes involves the same brain area in different dementias.…”