Disease Mechanisms: Sex differences

Create programs in basic, translational and clinical research aimed at comprehensive understanding of the impact of sex differences on the trajectories of brain aging and disease, phenotypes of AD and ADRD risk and responsiveness to treatment.

2023 PAR-17-033: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (R01) RFA-AG-21-029: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (R01) NOT-AG-20-038: Sex and Gender Differences in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) NOT-AG-21-050: Sex and Gender Differences in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) PAR-22-228: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (U01 Clinical Trial Optional) (Reissue of RFA-AG-21-029) PAR-23-082: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (U01 Clinical Trial Optional) (Reissue of PAR-22-228) PAR-25-224: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (U01 Clinical Trial Optional) 2.D Achieved Create programs in basic, translational and clinical research aimed at comprehensive understanding of the impact of sex differences on the trajectories of brain aging… DN 2015 AD Summit Recommendations: 1A News: Gene expression signatures of Alzheimer's disease Blog: Uterus plays a role in brain function, animal study shows

News: Small RNA regulates tau-related disease sex-differences in mouse models Four studies explore women’s brain and heart health during midlife Highlight: Potential contributor to sex differences in Alzheimer’s risk Highlight: Scientists show how electronic medical records may be used to learn more about Alzheimer’s disease NIA Event: Women's Health and Aging Q&A Workshop: Cognitive Aging Summit IV Workshop: Dementia with Lewy Bodies: Filling the Gaps in Translational and Clinical Research Research on Disease Mechanisms Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment Projects funded under RFA-AG-21-029 Sex-specific cognitive expression and risk in preclinical Alzheimer's disease 2016

  • Launch at least 12 new projects exploring the impact of sex differences on the trajectories of brain aging and disease, phenotypes of risk for AD and related dementias and responsiveness to treatment.

Summary of Key Accomplishments

AD is more prevalent in women compared to men; sex differences are known to affect the way that many diseases present in terms of symptoms and response to treatments. . NIA supports a robust program of basic and clinical research aimed at understanding the impact of sex differences on AD/ADRD etiology, presentation, and treatment. For example, an NIA initiative to solicit applications for basic and translational/clinical research towards a comprehensive understanding of the impact of sex differences on brain aging and AD/ADRD was renewed in FY 2025. In addition, in FY 2024 NIA awarded 15 new projects focused on sex differences in AD/ADRD, including studies of the interaction of sex and genetic factors with respect to AD risk; life-course studies involving the effects of hormonal activity from puberty through pregnancy and menopause on AD risk; and sex as a mediator of behavioral and social factors (e.g., economic mobility, exercise) and their association with AD/ADRD.

The key accomplishments summary is current as of September 2025.