Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic 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...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01684-z |
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| author | Cecilia Boccalini Debora Elisa Peretti Max Scheffler Linjing Mu Alessandra Griffa Nathalie Testart Gilles Allali John O. Prior Nicholas J. Ashton Henrik Zetterberg Kaj Blennow Giovanni B. Frisoni Valentina Garibotto |
| author_facet | Cecilia Boccalini Debora Elisa Peretti Max Scheffler Linjing Mu Alessandra Griffa Nathalie Testart Gilles Allali John O. Prior Nicholas J. Ashton Henrik Zetterberg Kaj Blennow Giovanni B. Frisoni Valentina Garibotto |
| author_sort | Cecilia Boccalini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ad1d015d9d584c47bfd2d0613b074491 |
| institution | OA Journals |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-ad1d015d9d584c47bfd2d0613b0744912025-08-20T02:15:07ZengBMCAlzheimer’s Research & Therapy1758-91932025-02-0117111110.1186/s13195-025-01684-zSex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic studyCecilia Boccalini0Debora Elisa Peretti1Max Scheffler2Linjing Mu3Alessandra Griffa4Nathalie Testart5Gilles Allali6John O. Prior7Nicholas J. Ashton8Henrik Zetterberg9Kaj Blennow10Giovanni B. Frisoni11Valentina Garibotto12Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Faculty of Medicine, Geneva University Neurocenter, University of GenevaLaboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Faculty of Medicine, Geneva University Neurocenter, University of GenevaDivision of Radiology, Geneva University HospitalsInstitute of Pharmaceutical Sciences, ETH ZurichLeenaards Memory Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneNuclear Medicine and Molecular Imaging, Lausanne University HospitalLeenaards Memory Center, Department of Clinical Neurosciences, Lausanne University Hospital and University of LausanneNuclear Medicine and Molecular Imaging, Lausanne University HospitalCentre for Age-Related Medicine, Stavanger University HospitalUK NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS FoundationDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgGeneva Memory Center, Geneva University HospitalsLaboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Faculty of Medicine, Geneva University Neurocenter, University of GenevaAbstract 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.https://doi.org/10.1186/s13195-025-01684-zSexNeuroimagingAlzheimer’s diseaseBiomarkerstau-PETWomen |
| spellingShingle | Cecilia Boccalini Debora Elisa Peretti Max Scheffler Linjing Mu Alessandra Griffa Nathalie Testart Gilles Allali John O. Prior Nicholas J. Ashton Henrik Zetterberg Kaj Blennow Giovanni B. Frisoni Valentina Garibotto Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study Alzheimer’s Research & Therapy Sex Neuroimaging Alzheimer’s disease Biomarkers tau-PET Women |
| title | Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study |
| title_full | Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study |
| title_fullStr | Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study |
| title_full_unstemmed | Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study |
| title_short | Sex differences in the association of Alzheimer’s disease biomarkers and cognition in a multicenter memory clinic study |
| title_sort | sex differences in the association of alzheimer s disease biomarkers and cognition in a multicenter memory clinic study |
| topic | Sex Neuroimaging Alzheimer’s disease Biomarkers tau-PET Women |
| url | https://doi.org/10.1186/s13195-025-01684-z |
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