A Stress and Pain Self-management m-Health App for Adult Outpatients with Sickle Cell Disease

项目总结/文摘

Project Summary/Abstract In response to PA-18-591-NOT-AG-20-034, our long-term goal is to understand the potential influence of unrecognized vascular cognitive impairment (VCI)/dementia on pain perception among adults with sickle cell disease (SCD) who are referred to a mHealth pain intervention study (1R01NR018848-01A1). The most typical reason for permanent neurological damage in patients with SCD is silent cerebral infarct, which occurs in approximately 39% of children by 18 years1 of age and over 50% of adults by 30 years of age.1 Vascular injury to the brain can directly modify pain processing by affecting ascending and descending nociceptive pathways2 and indirectly modify pain processing by affecting cognitive and emotional pathways.2 However, in patients with SCD, the effect of VCI/dementia on pain reports are virtually unknown because studies rarely include comprehensive neurocognitive testing or assessment of biomarker indicators of risk for dementia from vaso- occlusion-related silent cerebral infarcts and stroke, such as haptoglobin. The haptoglobin genotype (Hp1-1, Hp2-1, or Hp2-2) results in proteins with different structures, resulting in a differential ability to protect against and clear extracellular toxic hemoglobin (Hb). Understanding the biomarker indicators/genetic basis for VCI/dementia that may alter pain perceptions is pertinent for driving personalized therapies for patients, including those with SCD, Alzheimer's disease, or Alzheimer's disease-related dementia (AD/ADRD). In 90 adults with SCD who are referred to the m-Health study, the specific aims of this administrative supplement are to: Aim 1: Compare the proportion with VCI/dementia (neurocognitive status) among patients with Hp2-2 and patients with HP2-1 or Hp1-1. Aim 2: Compare (a) sensory pain perception (intensity, quality, neuropathic pain) and (b) concentrations of proinflammatory molecules among Hp2-2 genotype and Hp2-1 or Hp1-1 genotypes. We expect that more than half of the sample will have previously undetected VCI/dementia and that a larger proportion of patients with the Hp2-2 genotype will have VCI/dementia than those with the HP2-1 or Hp1-1 genotype. We also expect that the patients with HP2-2 will have worse pain and more pro- inflammatory molecules as compared to patients with HP2-1 or Hp1-1. These preliminary data will lead to an NIH-R01 focused on testing the hypothesis that Hp2-2 patients with SCD who have VCI/dementia will have worse pain and more pro-inflammatory molecules as compared to HP2-1 or Hp1-1 patients. Future studies will be designed to tease out the contributions of haptoglobin genotype and its regulation of pro-oxidative and pro- inflammatory properties of free hemoglobin to VIC/dementia in adult outpatients with SCD and pain. Other studies will be designed to test effects of transfusing the right Hp-typed blood (or isoform) on mitigation of many, if not all, the toxicity mediated by free hemoglobin and sickled cells. The impact of our findings would be enormous because they could be extrapolated to patients with AD/ADRD that currently affects 50 million individuals worldwide, with 10 million new cases diagnosed annually.3