Alzheimer's Supplement to ESRD-specific physiologic age

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ABSTRACT: RELEVANCE TO ADRD Only 13% of dialysis patients have normal cognition. Older end-stage renal disease (ESRD) patients are at risk for Alzheimer's disease and related dementias (ADRD) due to their advanced age, high burden of vascular disease, and comorbid conditions. Dialysis results in rapid fluid shifts that can lead to wide swings in blood pressure, cerebral atrophy, and brain injury; uremic metabolites are not fully cleared and impact cognitive function. Older dialysis patients have a 21-25% risk of a dementia diagnosis and 4-8% risk of an ADRD diagnoses; this is 19-fold and 7-fold higher than community-dwelling older adults without ESRD. Kidney transplantation (KT) is a growing treatment option for older adults with ESRD and improves cognitive function. However, even after careful pre-operative cognitive screening to identify the dialysis patients with existing dementia, post-KT incidence of dementia and ADRD is high. Compared to an ADRD risk of 0.6-0.9% for community-dwelling older adults, we found that 7.2-17.0% of older KT recipients received a diagnosis of ADRD. Yet, only half of patients who would meet diagnostic criteria for dementia receive a diagnosis suggesting that there is a substantial burden of undiagnosed ADRD among dialysis patients and KT recipients. An ADRD diagnosis doubles mortality risk for dialysis patients, and increases the risk of mortality and graft loss for KT recipients. ADRD is a clinical and public health challenge for this population, yet diagnosis of dementia notoriously underestimates the true incidence; <15% of ESRD patients with cognitive impairment have chart documentation. There is a clear knowledge gap surrounding which older ESRD patients will develop ADRD. Older ESRD patients experience a high burden of geriatric-specific risk factors for ADRD including frailty, depressive symptoms, and cognitive impairment. KT eliminates or reduces these ESRD-specific risk factors and improves cognitive function. However, there is a tradeoff: perioperative ADRD risk factors, like delirium and neurotoxic immunosuppression, may impact long-term ADRD risk. We will add novel assessments of ADRD and delirium to our prospective R01-funded study of frailty and aging among older (age≥55; n=3,000) KT candidates undergoing dialysis and older KT recipients, where global (MoCA) and domain-specific (TMT- A/B, AVLT) cognitive performance are already measured. We seek to: 1) To estimate the burden of pre- and post-KT dementia and ADRD among older ESRD patients; 2) To identify geriatric- and ESRD-specific ADRD risk factors among older ESRD patients; and 3) To test whether perioperative factors mediate the pre-KT risk for subsequent post-KT ADRD. Our findings will help clarify the risk factors and burden of ADRD among older ESRD patients. This work will be directly applicable to all older surgical patients who are at risk for perioperative complications like delirium and cognitive decline leading to long-term ADRD.