Neural Correlates of Letter and Semantic Fluency in Primary Progressive Aphasia

Area of Science:

• Neuroscience
• Cognitive Neurology
• Neuroimaging

Background:

• Verbal fluency (VF) tasks are crucial for assessing cognitive function.
• Previous studies on VF primarily involved stroke patients, necessitating research in other neurodegenerative conditions like primary progressive aphasia (PPA).
• PPA offers a unique model to study lesion-deficit associations due to distinct affected brain regions compared to stroke.

Purpose of the Study:

• To investigate the neuroimaging, clinical, and demographic factors associated with verbal fluency performance in patients with PPA.
• To differentiate the neural correlates of letter versus semantic fluency in the PPA population.
• To understand the role of disease severity in verbal fluency deficits within PPA.

Main Methods:

• Thirty-five patients diagnosed with PPA were included in the study.
• Participants completed letter and category verbal fluency tasks.
• Clinical assessments, demographic data collection, and structural MRI scans for volumetric analysis were performed.
• Stepwise regression models were employed to identify significant predictors of verbal fluency performance.

Main Results:

• Letter fluency was significantly associated with language severity (R² = 38%) and correlated with the volume of left superior temporal (R² = 12%) and right dorsolateral prefrontal regions (R² = 5%).
• Semantic fluency was predominantly associated with dementia severity (R² = 47%) and correlated with the volume of the left inferior temporal gyrus (R² = 7%).
• Clinical severity emerged as a critical factor in explaining verbal fluency performance in PPA, outweighing other demographic and clinical variables.

Conclusions:

• Letter fluency in PPA is associated with the volume of frontal and temporal brain areas, independent of overall disease severity.
• Semantic fluency in PPA is primarily linked to the volume of temporal lobe regions.
• Clinical severity plays a pivotal role in verbal fluency performance in PPA, highlighting its importance in cognitive assessment and management.