Alzheimer's Supplement to Hemodialysis-based interventions to preserve cognitive function

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ABSTRACT: RELEVANCE TO ADRD Over 640,000 US adults suffer from ESRD, >95% of whom receive hemodialysis (HD) for the rest of their life or until transplantation. Kidney disease and HD significantly impact cognitive function, especially higher-order executive function. Only 13% of HD patients have normal cognition; HD patients experience executive function impairment at a rate 3-fold higher than the general population, leading to hospitalization, disability, death and dementia. In fact, our preliminary data suggest that HD patients have a 21-25% lifetime risk of receiving a dementia diagnosis and 4-5% lifetime risk of receiving an Alzheimer's disease and related dementias (ADRD) diagnosis; they are 19-times and 7-times more likely to be diagnosed with dementia and ADRD, respectively than older adults without ESRD. Yet, only half of patients who would meet diagnostic criteria for dementia receive a diagnosis. Among HD patients, dementia and ADRD are major public health challenges. Studies of older adults suggest that the only effective interventions for preserving executive function and preventing ADRD are cognitive training (CT) and/or exercise training (ET). However, these modalities have not been tested in HD patients; even younger HD patients suffer substantial executive function impairment leading to dementia/ADRD and could benefit from the interventions. HD frequency (3 sessions a week) and duration (4-6 hours/session) makes HD patients a “captive audience” for intradialytic CT and/or ET to mitigate executive function decline and subsequent ADRD. To test the feasibility of intradialytic interventions, we conducted a pilot RCT of 20 HD patients, comparing standard of care to CT or ET; even in this pilot, we found that intradialytic CT and ET preserved executive function. As expected, executive function in patients receiving standard of care declined substantially by 3 months (difference=47.4 seconds, P=0.006); however, this decline was not seen among those receiving CT or ET. In just 3 months, CT and ET preserved executive function compared to a striking decline with standard of care. We have built upon this pilot study and are testing interventions on a wider breadth of HD patients, for longer durations, and alone versus in combination. Our ongoing RCT (98/200 participants enrolled) tests the impact of intradialytic CT, ET, and combined CT and ET on the executive function decline associated with HD. To this study we wish to add the novel endpoint of dementia/ADRD and ascertained through novel follow-up. We propose the following aims: To 1) add a novel secondary outcomes of dementia and ADRD to an existing RCT of intradialytic cognitive training (CT) and/or exercise training (ET); 2) To quantify the effects of intradialytic cognitive training (CT) and/or exercise training (ET) on dementia and ADRD among high-risk subgroups. Through this RCT, we will learn the impact of two potential non-pharmacological interventions, cognitive and exercise training, in preserving executive function during HD and the long-term outcome of dementia and ADRD.