The purpose of this FOA is to elucidate the etiology and pathogenesis of the neurocognitive complications associated with type 2 diabetes (T2D) with the ultimate goal of informing future strategies to mitigate the risk of these complications. Applications should propose expansions of ongoing human studies of well characterized T2D cohorts or cohorts comparing T2D with non-diabetic populations. Such expansions might include the addition of comprehensive neurocognitive measures (e.g., cognitive testing, neuroimaging, and biomarkers), clinical measures (e.g., insulin resistance, HbA1c), and/or collection of data on other risk factors (e.g., diet, obesity, micro- and macro-vascular disease, inflammation). It must be clearly explained how the collection of additional data will contribute to elucidation of the basis of neurocognitive sequelae of T2D.
Background: Emerging data have established links between T2D and neurocognitive impairment, including dementia. The current epidemic of dementia is driven, at least in part, by the concurrent epidemics of obesity, insulin resistance, T2D, and metabolic syndrome. Early research sought to elucidate the cause(s) for the apparent role of metabolic dysfunction in the increased prevalence of neurocognitive dysfunction and dementia, tentatively attributed to vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). Recent neuropathological research indicates that less than half of the variability in cognitive impairment in the years prior to death may be attributable to AD and other common pathologies, and it is unclear which pathologies are the primary drivers of the association between T2D and neurocognitive impairment and dementia.
Unlike other complications of T2D, neurocognitive complications of T2D have not clearly been demonstrated to correlate with measures of peripheral glycemia (with the exception of very poor glycemic control, HbA1c > 10%) and there is even less evidence for an association with other measures of peripheral glucose regulation (e.g., insulin concentration, insulin action, insulin resistance). The dearth of large-scale studies involving longitudinal assessment of T2D and associated risk factors for complications, neurocognition, and disease management has limited our knowledge of how specific parameters associated with T2D may lead to changes in brain structure and function and deficits in cognition, and how susceptibility to these brain changes may vary across the lifespan. Moreover, it can be difficult to distinguish the etiology of cognitive impairment since individuals with T2D are at increased risk of other associated complications (e.g., obesity, micro- and macro-vascular disease) that can affect cognition. Recent advances in neuroimaging, computerized neurocognitive assessment, and the availability of large, well-characterized cohorts with T2D could lead to improvements in characterizing brain structure/function, cognition, and clinical parameters and other risk factors associated with T2D. If specific parameters and other risk factors for adverse neurocognitive outcomes associated with T2D could be defined, treatment protocols could be developed to limit neurocognitive complications associated with T2D.
Types of ancillary studies might include, but are not limited to:
- Addition of metabolic and clinical phenotyping in individuals with T2D (e.g., measurement of insulin resistance, HbA1c), including associated factors of relevance to neurocognitive complications of T2D (e.g., diet, obesity, micro- and macro-vascular disease, inflammation), to studies that are already obtaining detailed measurement of neurocognition.
- Addition of cohorts with T2D and associated metabolic disease (insulin resistance, prediabetes) to studies that are already obtaining detailed measurement of neurocognition.
- Addition of comprehensive neurocognitive measures (e.g., cognitive testing, neuroimaging, and fluid-based biomarkers) to existing studies of T2D cohorts with well-characterized clinical correlates and course of disease.
Regardless of the type of study design, there must be a plan to measure the variables of interest in the same cohort at a minimum of two well justified time points. Cross sectional and purely correlative research is not consistent with the goals of this initiative.
Research that can examine how genetic and environmental factors confer risk or protect against the neurocognitive complications of T2D is encouraged. Research that addresses how neurocognitive complications of T2D impact academic and occupational function (where relevant) and activities of daily living, including the relationship to management of disease and/or treatment adherence is also encouraged.
Research across the lifespan and healthspan is appropriate for this FOA; however, it is possible that due to aging and disease-related factors, isolating mechanisms may be more complex and clinical targets less modifiable as individuals advance in age and disease burden increases. Therefore, there will be a special emphasis on research earlier in the developmental spectrum, especially prior to the development of complex disease (e.g., severe complications of T2D, CVD, dementia).
Strong expertise in T2D and associated disease processes (obesity, insulin resistance, prediabetes) and neuroscience is important for the research teams that will carry out the research supported by this FOA. It is anticipated that many of the funded research studies will involve the analysis and interpretation of complex, high-dimensional datasets. Therefore, it is strongly encouraged to include data scientists with relevant expertise on the research team. Collaborations between basic and clinical scientists are also encouraged but not required.
Deadlines: standard dates apply
URL: http://grants.nih.gov/grants/guide/pa-files/PAR-16-333.html
Filed Under: Funding Opportunities