Sex differences for clinical presentations and co-pathologies in four-repeat tauopathies

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Four-repeat (4R)-tauopathies present diverse clinical symptoms, often leading to misdiagnosis.
• Sex differences in Alzheimer's disease and other dementias are known, but understudied in 4R-tauopathies.

Purpose of the Study:

• To investigate sex differences in clinical presentation and co-pathologies within pathologically defined 4R-tauopathies.
• To assess the impact of sex on diagnostic accuracy for progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease.

Main Methods:

• Utilized National Alzheimer's Coordinating Center data for pathologically confirmed 4R-tauopathies.
• Analyzed sex differences in clinical presentation and co-pathologies for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilic grain disease (AGD), and Other-4R groups, adjusting for age and multiple comparisons.

Main Results:

• Clinical diagnoses frequently misidentified 4R-tauopathies, with no sex differences in diagnostic accuracy for PSP, CBD, AGD, or Other-4R groups.
• Females exhibited less cognitive decline, apathy, and motor symptoms, with later onset of changes compared to males.
• Males were more prone to Lewy body disease (LBD) co-pathology and associated clinical profiles.

Conclusions:

• Clinical diagnostic accuracy for 4R-tauopathies is low in both sexes.
• Females with 4R-tauopathies may present with milder clinical symptoms and reduced co-pathology compared to males.