Cognitive Decline and Incident Dementia in Older Patients with Secondary Hyperparathyroidism

继发性甲状旁腺功能亢进症老年患者的认知能力下降和痴呆

• 批准号: 10587339
• 负责人: Aarti Mathur
• 金额: $ 83.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587339
• 关键词: Accounting; Adult; Affect; Aftercare; Age; Alkaline Phosphatase; Ancillary Study; Binding; Biological Markers; Brain; Cardiovascular system; Clinical; Cognition; Cognitive; Computerized Medical Record; Data; Data Collection; Data Set; Decision Making; Decision Trees; Dementia; Diagnosis; Elderly; Eligibility Determination; End stage renal failure; Enrollment; Etiology; Fracture; Funding; Hospitalization; Impaired cognition; Infrastructure; Kidney Transplantation; Literature; Longitudinal cohort study; Measures; Mediating; Methods; Minerals; Modeling; Modification; Morbidity - disease rate; Nephrology; Neurocognitive; Neuropsychology; Odds Ratio; Older Population; Operative Surgical Procedures; Outcome; PTH gene; Parathyroidectomy; Patients; Persons; Pharmacotherapy; Physicians; Population; Process; Provider; Public Health; Risk; Risk Factors; Sampling; Secondary Hyperparathyroidism; Secondary to; Serum; Surgeon; Testing; Transplant Recipients; abstracting; clinical decision-making; clinical practice; cognitive function; cohort; dementia risk; design; disability risk; executive function; frailty; hazard; high risk; improved; individualized medicine; modifiable risk; mortality; novel; novel marker; older patient; patient oriented; pilot test; prognostication; prospective; receptor; risk stratification; systematic review; tool; treatment guidelines; usability; web-based tool

PROJECT SUMMARY Of the 400,000 older (age ≥55) adults living with end-stage renal disease (ESRD), 87% are cognitively impaired and 25% are subsequently diagnosed with dementia. Incident dementia in older ESRD patients is associated with a 1.5-fold higher risk of disability and 2-fold higher risk of hospitalization and mortality. Thus, identifying modifiable risk factors for cognitive decline is critical to the field of geriatric nephrology. A highly likely risk factor for cognitive decline and incident dementia is secondary hyperparathyroidism (SHPT), which affects nearly all ESRD patients. SHPT, characterized by high serum parathyroid hormone (PTH), is due to mineral abnormalities in ESRD. While PTH has been associated with cognitive impairment in non-ESRD populations we have found that median PTH levels are 54% higher in ESRD patients with cognitive impairment (p=0.03) and 2-fold higher in those who develop dementia. Furthermore, our preliminary data suggests that PTH increases other SHPT biomarkers, alkaline phosphatase (ALP, r=0.25, p<0.001) and FGF-23 (r=0.27, p=0.01), which also correlates with worse executive function (r=0.64, p=0.01). We hypothesize that PTH likely causes domain-specific cognitive decline both directly by binding to receptors in the brain and indirectly via release of other biomarkers. Yet, we found a paucity of high-quality studies of PTH, novel bio-markers, and cognition among ESRD patients in our systematic review; none evaluated cognitive trajectories. SHPT is modifiable with treatment including poly-pharmacotherapy, surgical parathyroidectomy (PTDx), or waiting until kidney transplant (KT) to reverse the etiology of SHPT. However, current SHPT treatment guidelines are inconsistent and ignore cognitive sequelae mainly due to the paucity of high-quality studies characterizing the impact of SHPT on cognitive function. Understanding the impact of SHPT on cognitive trajectories will allow for tailored treatment to mitigate cognitive decline, associated morbidity, and improve shared treatment decision- making among patients and treating surgeons, geriatricians, and nephrologists. Therefore, our central hypothesis is that SHPT contributes to cognitive decline and incident dementia in older ESRD patients and can be modified with treatment. This proposal will leverage and expand the scope of the oldest existing NIA-funded longitudinal cohort study of cognition and frailty among KT patients (3,062 SHPT patients) and prospectively enroll an additional 600 older SHPT patients in an ancillary study, in which, we will perform assessments of novel SHPT biomarkers and longitudinal, comprehensive assessments with a new neurocognitive battery to identify specific cognitive domains directly related to SHPT. We aim to: 1) To quantify the association between PTH and domain-specific cognitive trajectories among older SHPT patients 2) To test whether SHPT treatments impact cognitive outcomes, and 3) To develop a decision-making tool surrounding personalized SHPT treatment to mitigate cognitive decline. Novel incorporation of cognitive trajectories and SHPT biomarkers will transform practice and improve treatment decision-making in older ESRD patients.

项目总结