Clinicopathological correlates in frontotemporal dementia.

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Frontotemporal dementia (FTD) is a group of clinical syndromes.
• The relationship between FTD clinical and pathological subtypes is not well understood.
• Existing classifications may not reliably map clinical syndromes to pathologies.

Purpose of the Study:

• To reexamine the relationship between clinical and pathological subtypes of FTD.
• To determine if specific clinical phenotypes correlate with distinct pathological substrates.
• To assess the predictability of FTD pathology from clinical presentation.

Main Methods:

• Retrospective analysis of a large series (n=61) of FTD cases from two centers.
• Classification of clinical subtypes: behavioral variant FTD, semantic dementia, progressive nonfluent aphasia, corticobasal degeneration, and motor neuron disease.
• Classification of pathological subtypes based on tau- or ubiquitin-immunopositive inclusions, or lack of distinctive histology.

Main Results:

• Behavioral symptoms and semantic dementia were associated with diverse pathologies.
• Motor neuron disease predicted ubiquitinated inclusions.
• Parkinsonism/apraxia predicted corticobasal pathology, and nonfluent aphasia predicted Pick bodies.
• Some behavioral FTD cases unexpectedly presented with significant amnesia.

Conclusions:

• The pathological substrate of FTD can be predicted in a significant proportion of patients based on clinical presentation.
• This predictability has implications for developing targeted mechanistic treatments for FTD.
• Further research is needed to refine the understanding of FTD heterogeneity.