Cognitive Impairment after Kidney Transplant: a Hidden Consequence of Depression?

To the Editor,

In their recent study, Chu et al.¹ assessed the trajectory of cognitive performance after kidney transplant for people with and without significant frailty. Cognitive function was measured serially before and after transplant using the Modified Mini-Mental State Examination (3MS). Despite its many strengths, the two major findings of the study are currently less robust than the authors suggest.

The authors firstly conclude “both frail and nonfrail recipients experience short-term cognitive improvement post-transplant,” based upon repetition of the 3MS within 3 months. However, such short-term repetition is subject to a significant practice effect—i.e., implicit and explicit learning effects—such that the average person is expected to improve by 2.8 points on the 3MS when repeated at this interval.² Consequently, there is a risk that the observed improvement is an artifact of repeat cognitive testing, rather than a true change in participants’ cognitive ability.

Citing a previous study reporting a high prevalence of cognitive impairment in kidney transplant recipients,³ Chu et al. next report greater cognitive decline over 4 years in patients with higher baseline frailty. In neither study, however, were the results adjusted for depressive symptoms. This represents a key limitation for several reasons: Firstly, significant depressive symptoms are reported by nearly a third of people who have received a kidney transplant.⁴ Secondly, depressive symptoms commonly lead to deficits in attention, memory, and executive function, as well as poor effort on cognitive testing.⁵ Thirdly, the prevalence of depressive symptoms in the frail subgroup, who apparently experienced cognitive decline, was three times greater than the remaining participants at baseline, yet they were not retested after transplant. As such, the apparent cognitive decline observed in frail patients may in fact be a consequence of underlying depressive symptoms. Adjustment for depressive symptoms at 4-year follow-up, or even exclusion of those depressed at baseline, would help to refute this suggestion.

The influence of depression on cognitive function has important clinical implications for people who receive a kidney transplant. The adverse effects of depression on kidney transplant outcomes, including increased risk of mortality, are well established.⁴ If accounting for depression indeed attenuates the findings of this study, this suggests that depression could lead to morbidity and mortality through deleterious effects on cognitive function. As a common and treatable comorbidity in those receiving a kidney transplant, greater scrutiny of depression as a potential cause of cognitive impairment is warranted, both in this study and beyond.

Disclosures

None.