Cognitive problems of breast cancer survivors on proton pump inhibitors

Abstract

Purpose

Proton pump inhibitors (PPIs) are used in cancer patients to manage treatment-related gastrointestinal symptoms and to prevent damage to the gastric mucosal lining during treatment. However, PPI use may contribute to cognitive problems. To compare PPI-users and non-users, breast cancer survivors reported cognitive problems in three studies.

Methods

In Study 1, breast cancer survivors (N = 209; n = 173 non-users, n = 36 PPI-users; stages 0-IIIC) rated their cognitive function on the Kohli scale prior to cancer treatment, as well as one and two years later. In Study 2, women (N = 200; n = 169 non-users, n = 31 PPI-users, stages 0-IIIa, M = 11 months post-treatment) rated their cognitive function on the Kohli scale and BCPT checklist at three visits over a six-month period. In Study 3, participants (N = 142; n = 121 non-users, n = 21 PPI-users; stages I-IIIa, M = 4 years post-treatment) rated their cognitive function on the Kohli scale, BCPT checklist, and Functional Assessment of Cancer Therapy cognitive scale (FACT-cog).

Results

In Study 1, PPI-users reported more severe concentration problems (p = 0.039) but not memory problems (p = 0.17) than non-users. In Study 2, PPI-users reported more severe concentration problems (p = 0.022) than non-users, but not memory problems or symptoms on the BCPT (ps = 0.11). Study 3’s PPI-users reported more severe memory problems (p = 0.002), poorer overall cognitive function (p = 0.006), lower quality of life related to cognitive problems (p = 0.005), greater perceived cognitive impairment (p = 0.013), and poorer cognitive abilities (p = 0.046), but not more severe concentration problems (p = 0.16), compared to non-users.

Conclusions/implications

PPI use may impair breast cancer survivors’ memory, concentration, and quality of life.

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Abbreviations

PPI:

Proton Pump Inhibitor

BCPT:

Breast Cancer Prevention Trial

FACT-cog:

Functional Assessment of Cancer Therapy cognitive scale

References

  1. 1.

    Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336:2–3.

    Article  Google Scholar 

  2. 2.

    Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137:80–7.

    CAS  Article  Google Scholar 

  3. 3.

    Attwood S, Ell C, Galmiche J, Fiocca R, Hatlebakk J, Hasselgren B, et al. Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther. 2015;41:1162–74.

    CAS  Article  Google Scholar 

  4. 4.

    Sartori S, Trevisani L, Nielsen I, Tassinari D, Abbasciano V. Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. Cancer. 1996;78:1447–82.

    Article  Google Scholar 

  5. 5.

    Sartori S, Trevisani L, Nielsen I, Tassinari D, Panzini I, Abbasciano V. Randomized trial of omeprazole or ranitidine versus placebo in the prevention of chemotherapy-induced gastroduodenal injury. J Clin Oncol. 2000;18:463–3.

  6. 6.

    Wang B-Y, Zhang J, Wang J-L, Sun S, Wang Z-H, Wang L-P, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Exp Clin Cancer Res. 2015;34:85.

    Article  Google Scholar 

  7. 7.

    Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73:410–6.

    Article  Google Scholar 

  8. 8.

    Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265:419–28.

    Article  Google Scholar 

  9. 9.

    Kuller LH. Do proton pump inhibitors increase the risk of dementia? JAMA Neurol. 2016;73:379–81.

    Article  Google Scholar 

  10. 10.

    Batchelor R, Gilmartin JF, Kemp W, Hopper I, Liew D. Dementia, cognitive impairment and proton pump inhibitor therapy: a systematic review. J Gastroenterol Hepatol. 2017;32:1426–35.

    CAS  Article  Google Scholar 

  11. 11.

    Kohli S, Griggs JJ, Roscoe JA, Jean-Pierre P, Bole C, Mustian KM, et al. Self-reported cognitive impairment in patients with cancer. J Oncol Pract. 2007;3:54–9.

  12. 12.

    Savard J, Ganz PA. Subjective or objective measures of cognitive functioning—What’s more important? JAMA Oncol. 2016;2:1263–4.

    Article  Google Scholar 

  13. 13.

    Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004;26:955–69.

    Article  Google Scholar 

  14. 14.

    Shilling V, Jenkins V. Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer. Eur J Oncol Nurs. 2007;11:6–15.

    Article  Google Scholar 

  15. 15.

    Ferguson RJ, McDonald BC, Saykin AJ, Ahles TA. Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol. 2007;25:3866.

    Article  Google Scholar 

  16. 16.

    Stanton AL, Bernaards CA, Ganz PA. The BCPT symptom scales: a measure of physical symptoms for women diagnosed with or at risk for breast cancer. J Natl Cancer Inst. 2005;97:448–56.

    Article  Google Scholar 

  17. 17.

    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    CAS  Article  Google Scholar 

  18. 18.

    Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.

    Article  Google Scholar 

  19. 19.

    Mizyed I, Fass S, Fass R. Gastro-oesophageal reflux disease and psychological comorbidity. Aliment Pharmacol Ther. 2009;29:351–8.

    CAS  Article  Google Scholar 

  20. 20.

    McDermott LM, Ebmeier KP. A meta-analysis of depression severity and cognitive function. J Affect Disord. 2009;119:1–8.

    Article  Google Scholar 

  21. 21.

    Jenkins V, Shilling V, Fallowfield L, Howell A, Hutton S. Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study. Psycho-Oncology. 2004;13:61–6.

    Article  Google Scholar 

  22. 22.

    Greene-Schloesser D, Robbins ME. Radiation-induced cognitive impairment-from bench to bedside. Neuro-Oncol. 2012;14:iv37–44.

    Article  Google Scholar 

  23. 23.

    Rosano C, Simonsick EM, Harris TB, Kritchevsky SB, Brach J, Visser M, et al. Association between physical and cognitive function in healthy elderly: the health, aging and body composition study. Neuroepidemiology. 2005;24:8–14.

    Article  Google Scholar 

  24. 24.

    Deary IJ, Corley J, Gow AJ, Harris SE, Houlihan LM, Marioni RE, et al. Age-associated cognitive decline. Br Med Bull. 2009;92:135–52.

    Article  Google Scholar 

  25. 25.

    Evans DA, Beckett LA, Albert MS, Hebert LE, Scherr PA, Funkenstein HH, et al. Level of education and change in cognitive function in a community population of older persons. Ann Epidemiol. 1993;3:71–7.

    Article  Google Scholar 

  26. 26.

    Kiecolt-Glaser JK, Bennett JM, Andridge R, Peng J, Shapiro CL, Malarkey WB, et al. Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2014;32:1040–9.

    Article  Google Scholar 

  27. 27.

    Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, et al. Reliability and validity of the functional assessment of cancer therapy-breast quality-of-life instrument. J Clin Oncol. 1997;15:974–86.

    CAS  Article  Google Scholar 

  28. 28.

    Von Ah D, Tallman EF. Perceived cognitive function in breast cancer survivors: evaluating relationships with objective cognitive performance and other symptoms using the functional assessment of cancer therapy—cognitive function instrument. J Pain Symptom Manag. 2015;49:697–706.

  29. 29.

    Akter S, Hassan MR, Shahriar M, Akter N, Abbas MG, Bhuiyan MA. Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software. Alzheimers Res Ther. 2015;7:79.

    Article  Google Scholar 

  30. 30.

    Park S, Nam JH, Lee H, Chung H, Lee E, Shin J. Beyond uncertainty: negative findings for the association between the use of proton pump inhibitors and risk of dementia. J Gastroenterol Hepatol. 2019.

  31. 31.

    Hussain S, Singh A, Zameer S, Jamali MC, Baxi H, Rahman SO, et al. No association between proton pump inhibitors use and risk of dementia: evidence from a meta-analysis. J Gastroenterol Hepatol. 2019.

  32. 32.

    Gray SL, Walker RL, Dublin S, Yu O, Aiello Bowles EJ, Anderson ML, et al. Proton pump inhibitor use and dementia risk: prospective population-based study. J Am Geriatr Soc. 2018;66:247–53.

    Article  Google Scholar 

  33. 33.

    Kwa M, Plottel CS, Blaser MJ, Adams S. The intestinal microbiome and estrogen receptor–positive female breast cancer. JNCI J Natl Cancer Inst. 2016;108.

  34. 34.

    Parrilli G, Iaffaioli RV, Martorano M, Cuomo R, Tafuto S, Zampino MG, et al. Effects of anthracycline therapy on intestinal absorption in patients with advanced breast cancer. Cancer Res. 1989;49:3689–91.

    CAS  PubMed  Google Scholar 

  35. 35.

    Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors. Can Fam Physician. 2017;63:354–64.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Al-Qaisi M, Kahn A, Crowell M, Burdick G, Vela M, Ramirez F. Do recent reports about the adverse effects of proton pump inhibitors change providers’ prescription practice? Dis esophagus. 2018;

    Google Scholar 

  37. 37.

    Björnsson E, Abrahamsson H, Simren M, Mattsson N, Jensen C, Agerforz P, et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006;24:945–54.

    Article  Google Scholar 

  38. 38.

    Jackson MA, Goodrich JK, Maxan M-E, Freedberg DE, Abrams JA, Poole AC, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749–56.

    Article  Google Scholar 

  39. 39.

    Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701.

    CAS  Article  Google Scholar 

  40. 40.

    Marlicz W, Koulaouzidis A, Loniewski I, Koulaouzidis G. Letter by Marlicz et al Regarding Article,“Proton Pump Inhibitors Accelerate Endothelial Senescence.”. Circ Res. 2016;119:e31–2.

    CAS  Article  Google Scholar 

  41. 41.

    Rojo LE, Alzate-Morales J, Saavedra IN, Davies P, Maccioni RB. Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer’s disease. J Alzheimers Dis. 2010;19:573–89.

    CAS  Article  Google Scholar 

  42. 42.

    Badiola N, Alcalde V, Pujol A, Münter L-M, Multhaup G, Lleó A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8:e58837.

    CAS  Article  Google Scholar 

  43. 43.

    Fallahzadeh M, Borhani Haghighi A, Namazi M. Proton pump inhibitors: predisposers to Alzheimer disease? J Clin Pharm Ther. 2010;35:125–6.

    CAS  Article  Google Scholar 

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Funding

This study was supported in part by NIH grants: R01 CA186251, R01 CA126857, R01 CA131029, R01 CA186720, K05 CA172296, UL1RR025755, and T32 DE014320.

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Correspondence to Janice K. Kiecolt-Glaser.

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Madison, A.A., Woody, A., Bailey, B. et al. Cognitive problems of breast cancer survivors on proton pump inhibitors. J Cancer Surviv 14, 226–234 (2020). https://doi.org/10.1007/s11764-019-00815-4

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Keywords

  • Proton pump inhibitors
  • Breast cancer survivors
  • Cognitive symptoms, concentration, memory