Differences in Symptomatic Presentation and Cognitive Performance Among Participants With LATE-NC Compared to...

Area of Science:

• Neuroscience
• Neuropathology
• Geriatrics

Background:

• Transactive response DNA-binding protein 43 kDa (TDP-43) pathology characterizes FTLD-TDP and LATE-NC.
• Distinguishing clinical features between LATE-NC and FTLD-TDP is crucial for diagnosis and management.

Purpose of the Study:

• To compare the clinical presentations of autopsy-confirmed LATE-NC and FTLD-TDP.
• To identify distinct cognitive and behavioral symptoms associated with each TDP-43 proteinopathy.

Main Methods:

• Analysis of National Alzheimer's Coordinating Center data from 265 LATE-NC and 92 FTLD-TDP participants.
• Comparison of cognitive and behavioral symptoms stratified by Clinical Dementia Rating (CDR) global scores.

Main Results:

• LATE-NC participants were older, more likely to have APOE ε4 and Alzheimer's pathology, and had less severe final CDR scores.
• FTLD-TDP participants more frequently presented with primary progressive aphasia or behavioral issues (apathy, disinhibition).
• Severe LATE-NC cases showed more visuospatial impairment, delusions, and hallucinations compared to FTLD-TDP.

Conclusions:

• FTLD-TDP is generally more severe, affects younger individuals, and presents with distinct behavioral changes.
• LATE-NC, while potentially less globally severe, is associated with specific psychotic symptoms, particularly in advanced stages.