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Letters to the Editor
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Cognitive Impairment after Kidney Transplant: a Hidden Consequence of Depression?

Calum D. Moulton, Thahesh Tharmaraja, Jonathan L. Dumbrill and Christopher W. P. Hopkins
JASN August 2019, 30 (8) 1547-1548; DOI: https://doi.org/10.1681/ASN.2019030317
Calum D. Moulton
1Department of Psychological Medicine, King’s College London, London, UK;
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Thahesh Tharmaraja
2School of Medicine, University of Birmingham, Birmingham, UK;
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Jonathan L. Dumbrill
3Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; and
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Christopher W. P. Hopkins
4Psychological Medicine Service, Berkshire Healthcare National Health Service Foundation Trust, Royal Berkshire Hospital, Reading, UK
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  • depression
  • epidemiology and outcomes
  • dementia
  • transplantation

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.

Acknowledgments

Dr. Moulton is supported by the JMAS Sim Fellowship funded by the Royal College of Physicians of Edinburgh.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • See related Letter to the Editor, “Authors’ Reply,” on pages 1548–1549.

  • Copyright © 2019 by the American Society of Nephrology

References

  1. ↵
    1. Chu NM,
    2. Gross AL,
    3. Shaffer AA,
    4. Haugen CE,
    5. Norman SP,
    6. Xue Q-L, et al
    .: Frailty and changes in cognitive function after kidney transplantation. J Am Soc Nephrol 30: 336–345, 2019pmid:30679381
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Tombaugh TN
    : Test-retest reliable coefficients and 5-year change scores for the MMSE and 3MS. Arch Clin Neuropsychol 20: 485–503, 2005pmid:15896562
    OpenUrlCrossRefPubMed
  3. ↵
    1. Gupta A,
    2. Mahnken JD,
    3. Johnson DK,
    4. Thomas TS,
    5. Subramaniam D,
    6. Polshak T, et al
    .: Prevalence and correlates of cognitive impairment in kidney transplant recipients. BMC Nephrol 18: 158, 2017pmid:28499360
    OpenUrlPubMed
  4. ↵
    1. Zelle DM,
    2. Dorland HF,
    3. Rosmalen JG,
    4. Corpeleijn E,
    5. Gans RO,
    6. Homan van der Heide JJ, et al
    .: Impact of depression on long-term outcome after renal transplantation: A prospective cohort study. Transplantation 94: 1033–1040, 2012pmid:23064656
    OpenUrlCrossRefPubMed
  5. ↵
    1. Rock PL,
    2. Roiser JP,
    3. Riedel WJ,
    4. Blackwell AD
    : Cognitive impairment in depression: A systematic review and meta-analysis. Psychol Med 44: 2029–2040, 2014pmid:24168753
    OpenUrlCrossRefPubMed
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Journal of the American Society of Nephrology: 30 (8)
Journal of the American Society of Nephrology
Vol. 30, Issue 8
August 2019
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Cognitive Impairment after Kidney Transplant: a Hidden Consequence of Depression?
Calum D. Moulton, Thahesh Tharmaraja, Jonathan L. Dumbrill, Christopher W. P. Hopkins
JASN Aug 2019, 30 (8) 1547-1548; DOI: 10.1681/ASN.2019030317

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Cognitive Impairment after Kidney Transplant: a Hidden Consequence of Depression?
Calum D. Moulton, Thahesh Tharmaraja, Jonathan L. Dumbrill, Christopher W. P. Hopkins
JASN Aug 2019, 30 (8) 1547-1548; DOI: 10.1681/ASN.2019030317
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