Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: This study investigated sex differences in the associations between Alzheimer's disease (AD) biomarkers, cognitive performance, and decline in memory clinic settings. METHODS: 249 participants (females/males:123/126), who underwent tau-PET, amyloid-PET, structural MRI, and plasma glial fibrillary acidic protein (GFAP) measurement were included from Geneva and Lausanne Memory Clinics. Mann-Whitney U tests investigated sex differences in clinical and biomarker data. Linear regression models estimated the moderating effect of sex on the relationship between biomarkers and cognitive performance and decline. Sex differences in cognitive decline were further evaluated using longitudinal linear mixed-effect models with three-way interaction effects. RESULTS: Women and men present similar clinical features, amyloid, and neurodegeneration. Women had higher tau load and plasma levels of GFAP than men (p < 0.05). Tau associations with amyloid (standardized β = 0.54,p < 0.001), neurodegeneration (standardized β=-0.44,p < 0.001), and cognition (standardized β=-0.48,p < 0.001) were moderated by a significant interaction with sex. Specifically, the association between amyloid and tau was stronger among women than men (standardized β=-0.19,p = 0.047), whereas the associations between tau and cognition and between tau and neurodegeneration were stronger among men than in women (standardized β=-0.76,p = 0.001 and standardized β=-0.56,p = 0.044). Women exhibited faster cognitive decline than men in the presence of severe cortical thinning (p < 0.001). CONCLUSION: Women showed higher tau load and stronger association between amyloid and tau than men. In individuals with high tau burden, men exhibited greater neurodegeneration and cognitive impairment than women. These findings support that sex differences may impact tau deposition through an upstream interplay with amyloid, leading to downstream effects on neurodegeneration and cognitive outcomes.
Source: Alzheimer s Research & Therapy
Institutions: University of Geneva, University Hospital of Geneva, ETH Zurich, Institute of Pharmaceutical Sciences, Centre Hospitalier Universitaire Vaudois, École Polytechnique Fédérale de Lausanne, University of Lausanne, King's College London, Stavanger University Hospital, University of Gothenburg, University of Wisconsin–Madison, Sahlgrenska University Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, University of Science and Technology of China, Sorbonne Université, Pitié-Salpêtrière Hospital, Institut du Cerveau, Centre d'Imagerie BioMedicale
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
Awards: Neuroinflammatory plasma and molecular imaging biomarkers as diagnostic and prognostic tool in cognitive impairment, The Biological Basis of Cognitive Impairment due to Suspected Non-Alzheimer’s Pathology (SNAP) : Studying the interplay between amyloidosis and tau-related neurodegeneration, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): correlation with clinical features and in vivo neuropathology, G880118091, Arizona Alzheimer's Disease Research Center
OpenAlex ID: W4407702950