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Clinical Manifestations.

Carmela Tartaglia1

  • 1Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; Krembil Brain Institute, University Health Network, Toronto, ON, Canada; Toronto Dementia Research Alliance, Toronto, ON, Canada.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Sex and gender significantly impact frontotemporal lobar degeneration (FTLD) subtypes, affecting prevalence, clinical presentation, and progression. Understanding these differences is key for developing targeted therapies and improving patient outcomes.

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Area of Science:

  • Neuroscience
  • Genetics
  • Neurology

Background:

  • Sex and gender differences are increasingly recognized across neurodegenerative diseases.
  • Frontotemporal lobar degeneration (FTLD) encompasses diverse syndromes with behavioral, language, and motor impairments.
  • These sex and gender differences manifest uniquely across FTLD subtypes.

Purpose of the Study:

  • To provide a comprehensive overview of how sex and gender influence FTLD.
  • To integrate insights from epidemiology, genetics, neuroimaging, and biomarker studies.
  • To highlight the need for sex-stratified approaches in FTLD research.

Main Methods:

  • Review of epidemiological data on FTLD prevalence across subtypes.
  • Analysis of genetic influences on sex differences in FTLD.
  • Examination of neuroimaging and biomarker studies stratified by sex.
  • Integration of clinical phenotype and disease progression data based on sex.

Main Results:

  • Behavioral variant frontotemporal dementia (bvFTD) shows a 2:1 male-to-female ratio in sporadic cases, which normalizes in genetic forms.
  • Progressive supranuclear palsy (PSP) has a male predominance (1.5:1).
  • Sex influences clinical presentation (e.g., disinhibition vs. apathy in bvFTD) and disease progression (e.g., motor vs. cognitive deficits in PSP).
  • Sex differences are also observed in biomarker profiles and are influenced by genetic mutations (GRN, C9orf72, MAPT).

Conclusions:

  • Understanding sex and gender differences in FTLD is crucial for advancing precision medicine.
  • Tailored therapeutic strategies informed by sex-specific data can improve disease management.
  • Further research is needed to fully elucidate and leverage these sex-based variations for better patient outcomes.