This Funding Opportunity Announcement (FOA) supports mechanistic and early translational research focused on a more rigorous in-depth examination of the potential interactions of environmental toxins with genetic and non-genetic molecular targets known to influence Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD). It is expected that these studies will address the clinical relevance of these exposures on disease initiation, progression, or modification. Anticipated outcomes include an improved understanding of neurological mechanisms of chemical toxicities related to AD/ADRD, more evidence-based potential biomarkers of exposure and toxicity for those most at risk, as well as more data to support causality and potential approaches for mitigation. The scope of research includes mechanistic studies on the modification of known AD/ADRD targets by neurotoxins of concern, and conversely, whether known targets for these neurotoxins play a role in etiologies of AD/ADRD. The development and validation of neuropathological, neurophysiological and neurobehavioral animal models that simulate potential toxin exposures in humans is another example of supported studies. Preclinical studies of interactions of environmental toxicant with AD/ADRD in pilot human subject studies (that do not meet the NIH definition of clinical trial) are appropriate for this FOA. Interdisciplinary collaboration is required to address the various fields of study related to this research, e.g., neuroscience, aging, and environmental health sciences.

The purpose of this FOA is to provide support for institutional research training programs in Alzheimers Disease/Alzheimers Disease-Related Dementias (AD/ADRD). These institutional research training programs should produce well-trained neuroscientists who leave the program with the research skills and scientific knowledge to make a significant contribution to research on AD/ADRD cognitive impairment and dementia. Programs should be designed to enhance the breadth and depth of training across the spectrum AD/ADRD research areas (e.g. AD, Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementia (LBD), Fronto-temporal Dementia (FTD) and mixed dementias) by incorporating didactic, research and career development components within this theme into a program that fosters exceptional research skills and knowledge. Programs may support basic, clinical and/or translational research. Programs supported by this FOA must include formal components to ensure a thorough understanding of experimental design, statistical principles and methodological approaches, analytical skills, and skills for communicating science, both orally and in writing, to a wide variety of audiences. All programs are expected to design and/or provide opportunities and activities that will foster the development of quantitative literacy and the application of quantitative approaches to the trainees' research. These training programs are intended to be 2 years in duration and support training of one or more of the following groups: dissertation stage predoctoral students in their 3rd and/or 4th year of graduate school, postdoctoral fellows and fellowship-stage clinicians. (NINDS does not support first or second year graduate students under this FOA).

The purpose of the NINDS Alzheimers Disease and Alzheimers Disease-Related Dementias (AD/ADRD) Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program is to support of a cohort of new and talented, independent investigators from diverse backgrounds conducting AD/ADRD research. The program is designed to facilitate a timely transition of promising postdoctoral researchers from diverse backgrounds (e.g., see NIHs Interest in Diversity) from their mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. The program will provide independent NIH research support during this transition in order to help awardees establish independent research programs in the AD/ADRD field. This FOA is designed specifically for applicants proposing research that does not involve leading an independent clinical trial, a clinical trial feasibility study, or an ancillary study to a clinical trial. Applicants to this FOA are permitted to propose research experience in a clinical trial led by a mentor or co-mentor.

Gastrointestinal (GI) complications in children and adults with neurodevelopmental disorders have drawn attention to gaps in understanding their causes and treatment. GI dysfunction is particularly common in individuals with neurodevelopmental disorders such as autism, Fragile X syndrome, and Rett syndrome, as well as chromosomal disorders such as Down syndrome. GI disorders in these conditions can include gut malformations present at birth (such as pyloric stenosis or Hirschsprung disease) but also functional issues such as feeding problems, gastro-esophageal reflux disease (GERD), cyclic vomiting, delayed gastric emptying, diarrhea, bloating, celiac disease, irritable bowel symptoms, and constipation leading to encopresis, incontinence, and stool impaction. These GI issues may be associated with severe nutritional deficiencies, weight loss, and failure to thrive. GI symptoms are reported in between 23-70% of individuals with autism, a rate ~ 8 times higher than in the general population, with similar rates in individuals with other less common forms of intellectual and developmental disabilities (IDD) (Holingue et al., Autism Res 2018:11:24-36). Unfortunately, mechanisms to accurately diagnose GI conditions in this population are limited, and tailored treatments to address them are almost nonexistent, particularly since clinical trials for IDD populations are rare.