Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology

Area of Science:

• Neuroscience
• Neuropathology
• Clinical Neurology

Background:

• Frontotemporal lobar degeneration (FTLD) presents with diverse pathologies, primarily aggregated TAR DNA-binding protein-43 (TDP-43), tau, or fused in sarcoma (FUS).
• Predicting FTLD pathology from clinical presentation remains challenging.

Purpose of the Study:

• To investigate the correlation between specific clinical symptoms, including neuropsychiatric features, and underlying FTLD pathology.
• To determine if clinical presentation can predict molecular subtypes of FTLD.

Main Methods:

• A cohort of 150 brain donors with frontotemporal dementia was analyzed.
• Clinical symptoms, including neuropsychiatric features like hallucinations and delusions, were scored and compared across pathological groups (TDP-43, tau, FUS, and non-FTLD).

Main Results:

• Hyperorality was a significant indicator of FTLD pathology versus non-FTLD pathology.
• Hallucinations in early disease stages were associated with TDP-43 pathology, including C9orf72 repeat expansion carriers.
• Perseverative or compulsive behaviors were more prevalent in specific TDP-43 histotypes (TDP-B and TDP-C).

Conclusions:

• Neuropsychiatric symptoms are prevalent in FTLD and serve as valuable indicators of specific underlying pathologies.
• Routine assessment of neuropsychiatric symptoms in frontotemporal dementia patients is recommended to improve diagnostic accuracy and patient stratification for clinical trials.