COG-01 Phenotypic variation in 
ALS-FTD and effect on survival

Area of Science:

• Neurology
• Neuroscience
• Clinical Medicine

Background:

• Amyotrophic Lateral Sclerosis-Frontotemporal dementia (ALS-FTD) spectrum exhibits significant heterogeneity in clinical presentation and survival rates.
• Understanding the impact of initial symptoms on disease trajectory is crucial for patient management and research.

Purpose of the Study:

• To investigate how initial motor versus cognitive symptoms influence survival in ALS-FTD.
• To compare cognitive, behavioral, and structural brain differences between ALS-FTD and behavioral variant Frontotemporal Dementia (bvFTD) cohorts.

Main Methods:

• 98 patients (59 ALS-FTD, 39 bvFTD) underwent cognitive and behavioral assessments.
• ALS-FTD initial presentation was categorized as motor or cognitive based on symptoms and carer reports.
• Survival data and MRI-based brain atrophy patterns (motor cortex, prefrontal cortex) were analyzed.

Main Results:

• 69% of ALS-FTD patients presented with initial cognitive symptoms; 31% with motor symptoms.
• Motor onset ALS-FTD had significantly shorter survival (33 months) than cognitive onset (63 months).
• ALS-FTD showed reduced language, verbal fluency, naming, and emotion processing compared to bvFTD; motor cortex atrophy correlated with reduced survival.

Conclusions:

• Initial motor presentation in ALS-FTD is associated with faster disease progression and shorter survival compared to cognitive presentation.
• Motor cortex atrophy is a key factor in ALS-FTD progression and survival.
• Findings aid in categorizing ALS-FTD patients into fast and slow progressors for clinical trials.