Frailty and Changes in Cognitive Function after Kidney Transplantation

Abstract

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.

Keywords: cognition; frailty; kidney transplantation.

Figure 1.

Global cognitive trajectories (Modified Mini-Mental State Examination [3MS] scores) improve among all adult kidney transplant (KT) recipients post-KT (n=665) in the short-term. Adjusted trajectories were estimated for 665 KT recipients ages 18+ years old using a mixed effects model with random slope (time) and intercept (person) controlling for baseline age (centered at 55 years old), sex, race, education, self-reported quality of life, donor type (live or deceased), the Charlson Comorbidity Index adapted for patients with ESRD,^, and recipient eGFR at the time of admission and discharge as well as immunosuppressive medications (induction and triple therapy including tacrolimus, mycophenolate mofetil, and steroid). We accounted for nonlinearity by using splines to examine trajectories over several different time periods: the first 3 months, 3–6 months, 6 months to 1 year, and 1–4 years post-KT. Baseline (time 0) represents the time of KT admission or “pre-KT.” The thick line represents the average overall global cognitive trajectory across time; thin lines represent the 95% confidence intervals (95% CIs). KT recipients had significant improvements in cognitive performance in the first 3 months post-KT. *Rates of change (points per week) that are statistically significant within the respective interval at a cutoff of P=0.05.

Figure 2.

Global cognitive trajectories (Modified Mini-Mental State Examination [3MS] scores) vary by frailty status among adult kidney transplant (KT) recipients post-KT (n=665). Adjusted trajectories were estimated for 565 nonfrail and 100 frail KT recipients ages 18+ years old using a mixed effects model with random slope (time) and intercept (person) controlling for baseline age (centered at 55 years old), sex, race, education, self-reported quality of life, donor type (live or deceased), the Charlson Comorbidity Index adapted for patients with ESRD,^, and recipient eGFR at the time of admission and discharge as well as immunosuppressive medications (induction and triple therapy including tacrolimus, mycophenolate mofetil, and steroid). We accounted for nonlinearity to examine trajectories over different time periods: the first 3 months, 3–6 months, 6 months to 1 year, and 1–4 years post-KT. Baseline (time 0) represents pre-KT. Both frail and nonfrail recipients improved in cognitive function within 3 months post-KT. However, between 1 and 4 years post-KT, frail recipients experienced declines in cognitive function, whereas nonfrail KT recipients plateaued; those cognitive trajectories significantly differed. *Significantly different rates of change (points per week) comparing frail with nonfrail within the respective interval (P<0.05).