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

Area of Science:

• Neuroscience
• Neurology
• Cognitive Science

Background:

• Semantic dementia (SD) is a progressive neurodegenerative disorder characterized by semantic memory loss, classified under frontotemporal dementia.
• SD was clinically defined less than 50 years ago, making recent research crucial for understanding its progression and pathology.

Purpose of the Study:

• To review recent advancements in neuroimaging, pathology, and genetics of semantic dementia.
• To highlight SD's potential as a target for disease-modifying interventions due to its distinct characteristics.

Main Methods:

• Review of recent neuroimaging studies, including structural MRI and functional MRI (fMRI).
• Analysis of pathological findings, focusing on protein aggregates like TDP-43.
• Examination of genetic research to determine the prevalence of genetic causes in SD.

Main Results:

• Neuroimaging shows characteristic asymmetrical atrophy, typically left-lateralized, in the anterior temporal pole and fusiform gyrus.
• fMRI reveals altered connectivity in anterior temporal regions and relative preservation of frontal/parietal areas.
• Strong clinicopathological concordance is observed, with TDP-43 type C being the most common subtype; genetic causes are rare.

Conclusions:

• Semantic dementia exhibits a relatively clear diagnostic profile, clinical course, and pathological homogeneity.
• These features position SD as a promising candidate for novel therapeutic strategies.
• Developing individual-level neuroimaging markers for disease progression is essential for future research and treatment development.