Cognitive prehabilitation to prevent Alzheimer's disease after kidney transplantation

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ABSTRACT Of the 130,000 older (≥50) kidney transplant (KT) recipients in the US, we have estimated that 19% experience post-KT cognitive decline putting them at elevated risk of Alzheimer’s disease and related dementias (ADRD). Compared to a 10-year ADRD risk of 0.6-0.9% for community-dwelling older adults, the risk of ADRD diagnosis is 1.0%-6.7% for older recipients; overall, 7.2-17.0% of older recipients receive a dementia diagnosis within 10 years of KT. Yet, the true burden of ADRD is substantially higher given that only half of patients who would meet diagnostic criteria for dementia receive a diagnosis. A post-KT ADRD diagnosis leads to disability and dependence, and increases a patient’s risk of mortality 2.4-fold and their risk of graft loss 1.5-fold. Within 10 years of an ADRD diagnosis, 88.6% of older recipients have died and 38.9% have experienced graft loss. These preliminary data arise from my current NIH funded research: 1. Prospective cohort study: 12-year-old study of frailty and cognitive function among KT patients; and 2. RCT: 2x2 factorial RCT of interventions to preserve cognitive function among patients initiating hemodialysis. I have established a strong track record and built a research program at the intersection of aging and renal epidemiology which serves as a foundation for this mid-career Independent Scientist (K02) award application. Through this research I have realized that focusing on physical aging without also understanding cognitive aging provides an incomplete picture of older KT patients. As I transition to more administrative duties in 2022, I am unable to expand to ADRD research and develop collaborative relationships with neurocognitive investigators. This K02 will advance my research career by affording me the opportunity for dedicated time to concentrate efforts on career development to expand my research portfolio to include ADRD. My long-term career objective is to establish a sustainable research program focused on physical and cognitive aging among KT recipients. To accomplish these goals, I seek protected time to acquire the knowledge and skills needed: 1. To integrate ADRD research into my existing research portfolio; 2. To develop scientific protocols to study cognitive prehabilitation for older KT recipients; and 3. To establish a national renal aging research network that will collaborate on new research and mentor junior faculty. By replacing administrative duties with protected time, the K02 mechanism will allow me to achieve my long-term career goal of establishing a sustainable research program focused on physical and cognitive aging among KT patients. I will take full advantage of what the K02 Independent Scientist mechanism offers: training in ADRD research, developing a sustainable research infrastructure, and ultimately impacting the lives of the 100,000 patients who experience physical and cognitive decline while waiting for KT.