Clinical Manifestations.

Area of Science:

• Neuroscience
• Neurology
• Clinical Research

Background:

• Behavioral variant frontotemporal dementia (bvFTD) is a progressive neurodegenerative disorder characterized by behavioral and executive function changes.
• Predicting bvFTD progression is challenging due to its heterogeneous nature.
• While age and genetics are known factors, the impact of specific symptoms on progression is less understood.

Purpose of the Study:

• To identify specific neuropsychiatric, motor, and cognitive symptoms associated with rapid bvFTD progression over one year.
• To determine which symptoms are most predictive of fast disease advancement.

Main Methods:

• Utilized data from 192 bvFTD participants from the ARTFL-LEFFTDS study, classifying them as fast or slow progressors.
• Employed random forest modeling to identify key predictive symptoms from a list of 43 features.
• Assessed model performance using AUC, sensitivity, specificity, and other metrics, and used logistic regression to evaluate incremental predictive value.

Main Results:

• The top 5 predictive features for fast bvFTD progression included impaired verbal and working memory, compulsive behaviors, irritability, and impaired mental flexibility.
• A model using these 5 features achieved an AUC of 0.75, demonstrating significant predictive power.
• Adding these key symptoms to demographic and clinical variables substantially improved the prediction of fast progression.

Conclusions:

• Impaired memory (verbal and working), compulsive behaviors, and irritability are strong indicators of faster bvFTD progression.
• These symptoms are more effective than demographic factors alone in distinguishing rapid vs. slow disease advancement.
• These findings can inform targeted early interventions, family education, and management strategies for bvFTD patients.