Frailty and Changes in Cognitive Function after Kidney Transplantation
Authors: Chu Nadia M. , Gross Alden L. , Shaffer Ashton A. , Haugen Christine E. , Norman Silas P. , Xue Qian-Li , Sharrett A. Richey , Carlson Michelle C. , Bandeen-Roche Karen , Segev Dorry L. , McAdams-DeMarco Mara A. 
Published: January 2019

Significance Statement
Frailty is a predictor of adverse outcomes in kidney transplant populations. Although restoration of kidney function after transplant generally improves cognitive function, it seems plausible that, in frail individuals, stressors related to surgery and immunosuppression might mitigate short-term cognitive improvement and contribute to possible subsequent decline. The authors found significantly lower pretransplant cognitive scores in frail kidney transplant recipients compared with nonfrail recipients. Although both groups showed cognitive improvement by 3 months post-transplant, cognitive function plateaued for nonfrail recipients between 1 and 4 years after transplant and declined for frail recipients. By 4 years post-transplant, cognitive scores were significantly lower among frail versus nonfrail recipients. Transplant centers are encouraged to apply available evidence-based strategies to reduce risk of cognitive impairment among frail transplant recipients.

Background
Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft.

Methods
In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. To investigate potential short- and medium-term effects of frailty on post-transplant cognitive trajectories, we measured cognitive function up to 4 years post-transplant. Using an adjusted mixed effects model with a random slope (time) and intercept (person), we characterized post-transplant cognitive trajectories by pretransplant frailty, accounting for nonlinear trajectories.

Results
Of 665 recipients (mean age 52.0 years) followed for a median of 1.5 years, 15.0% were frail. After adjustment, pretransplant cognitive scores were significantly lower among frail patients compared with nonfrail patients (89.0 versus 90.8 points). By 3 months post-transplant, cognitive performance improved for both frail (slope =0.22 points per week) and nonfrail (slope =0.14 points per week) recipients. Between 1 and 4 years post-transplant, improvements plateaued among nonfrail recipients (slope =0.005 points per week), whereas cognitive function declined among frail recipients (slope =−0.04 points per week). At 4 years post-transplant, cognitive scores were 5.8 points lower for frail recipients compared with nonfrail recipients.

Conclusions
On average, both frail and nonfrail recipients experience short-term cognitive improvement post-transplant. However, frailty is associated with medium-term cognitive decline post-transplant. Interventions to prevent cognitive decline among frail recipients should be identified.