August 5, 2020
PAR-19-070 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
PAR-19-071 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R21 Clinical Trial Not Allowed)
National Institute on Aging (NIA)
This Notice of Special Interest (NOSI) is intended to promote multidisciplinary research to clarify sex and gender differences in the risk, development, progression, diagnosis, and clinical presentation of Alzheimer's disease or Alzheimer's disease-related dementias (AD/ADRD). Studies that examine sex and gender differences in outcomes (e.g., clinical, functional, well-being) among people living with AD/ADRD are also relevant. Broad areas of interest include biological (e.g., hormonal, genetic, metabolic, comorbidity-related), neuroscientific (e.g., neural systems and functions), behavioral (e.g., physical activity, substance use, social engagement), social (e.g., history of maltreatment or adversity, child rearing, marital status, education, employment), psychological (e.g., depression, cognitive ability, emotional function, stress reactivity, personality), and healthcare profession (e.g., provider knowledge and attitudes about dementia) and healthcare system-level (e.g., access to care) factors and processes that separately or together may drive observed differences by sex and gender and/or may operate differently by sex and gender. Studies that account for methodological and measurement issues that may drive sex and gender differences are also of interest.
Studies that are using systems-based, data-driven approaches to understand the molecular mechanisms by which sex differences impact AD/ADRD risk and responsiveness to various types of pharmacologic and non-pharmacologic treatments for AD/ADRD are more appropriate for RFA-AG-21-029.
For the purpose of this NOSI:
Understanding sex and gender differences in AD/ADRD is critical for research recommendations to diversify research cohorts and improve methods and tools for conducting health disparities research related to AD/ADRD. These recommendations are found in the National Alzheimer’s Project Act, the 2012 Alzheimer’s Disease Research Summit, the health disparities session of the 2013 Alzheimer’s Disease and Related Dementias Meeting, the 2015 Alzheimer’s Disease Research Summit, the 2018 Alzheimer’s Disease Research Summit, and NIA’s ADRD Research Implementation Milestones.
A core challenge of understanding sex and gender differences in processes and outcomes related to AD/ADRD is that the terms “sex” and “gender” are often used interchangeably. However, “sex” refers to biological factors and processes (e.g., sex chromosomes, endogenous hormonal profiles) related to differentiation between males and females, whereas “gender” refers to culturally- and socially-defined roles that sometimes influence how individuals see themselves (gender identity); the perceptions, attitudes, and expectations of others (gender norms); and social interactions (gender relations).
A lack of clarification on “sex” and “gender” can obfuscate the identification of specific biological and neural systems and psychological, behavioral, sociocultural, and environmental pathways that may help identify individuals at higher risk of AD/ADRD as well as potential differences in disease progression. Ultimately, understanding the unique roles of sex and gender may facilitate the identification of therapeutic targets and interventions. For example, prior work suggests, but does not definitively indicate, that women may be at higher risk for AD/ADRD than men. Women’s survival advantage may explain part, but not all, of their potential elevated AD/ADRD risk, as age is the strongest risk factor for AD/ADRD. This survival advantage itself is thought to be a combination of biological factors (i.e., sex differences) which drive female survival advantages in many species, as well as a host of non-biological factors (i.e., gender differences). These gender differences include factors such as smoking, which until relatively recently was far more common among men than women. As the gender gap in smoking has narrowed as a result of societal change in the range of acceptable behavior for women in some societies, women’s longevity advantage over men has also decreased. How these and other gendered processes (e.g., changes in educational attainment, employment) and structural gender inequalities (e.g., barriers to access healthcare services and high-quality care) will impact AD/ADRD outcomes such as overall population prevalence of AD/ADRD and gender differences in AD/ADRD over time are unknown. Other unanswered questions include how a variety of putative risk (e.g. low education, depression) and protective (e.g., social connectedness, self-regulation) factors for AD/ADRD operate along sex and gender lines. Finally, questions remain about the best methodological and measurement assessments in epidemiological and other studies to evaluate sex and gender in AD/ADRD, including survival bias, competing risks, and sample selection.
Example research topics that may elucidate sex and/or gender differences in AD/ADRD risk, development, progression, diagnosis, clinical presentation, and outcomes include, but are not limited to, the following:
Application and Submission Information
This notice applies to due dates on or after November 12, 2020 and subsequent receipt dates through November 13, 2021.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice:
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
National Institute on Aging (NIA)