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Clinical Manifestations.

Xulin Liu1,2, Sterre C M de Boer3,4,5, Carmela Tartaglia1,2

  • 1University Health Network, Toronto, ON, Canada.

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

Sex differences in Alzheimer's disease (AD) presentation exist, with females showing more executive deficits and males more behavioral disturbances. Recognizing these variations is key for accurate AD diagnosis and management.

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Area of Science:

  • Neuroscience
  • Neurology
  • Gerontology

Background:

  • Behavioral variant frontotemporal dementia (bvFTD) shows an imbalanced sex ratio and differing symptoms between sporadic and genetic cases, especially in females.
  • Females without genetic mutations may be misdiagnosed with Alzheimer's disease (AD) due to atypical bvFTD symptom presentation.

Purpose of the Study:

  • To investigate sex-based differences in the clinical and cognitive presentation of Alzheimer's disease (AD).
  • To explore potential diagnostic misclassification in females with atypical bvFTD-like symptoms presenting as AD.

Main Methods:

  • Analysis of the National Alzheimer's Coordinating Center (NACC) dataset (N=11,286) including sex-stratified evaluation of neuropsychiatric symptoms (NPI-Q) and cognitive function.
  • Subgroup analyses for early-onset AD (age < 65) and late-onset AD, with corrections for age, disease severity, and education.

Main Results:

  • Females exhibited more severe executive deficits and depression compared to males.
  • Males showed more severe irritability, apathy, disinhibition, agitation, and nighttime behavioral disturbances.
  • Early-onset AD males presented with more severe motor disturbances, disinhibition, and delusions.

Conclusions:

  • Significant sex-related differences in AD symptom presentation, including cognitive and behavioral aspects, were identified.
  • These sex-specific differences may lead to diagnostic challenges, particularly misclassifying females with bvFTD-like symptoms as AD.
  • Enhanced recognition of sex-based symptom variability is crucial for improving diagnostic accuracy and patient management in AD.