Abstract
Cognitive dysfunction has been one of the most reported and studied adverse effects of cancer treatment, but, for many years, it was overlooked by the medical community. Nevertheless, the medical and scientific communities have now recognized that the cognitive deficits caused by chemotherapy have a strong impact on the morbidity of cancer treated patients. In fact, chemotherapy-induced cognitive dysfunction or ‘chemobrain’ (also named also chemofog) is at present a well-recognized effect of chemotherapy that could affect up to 78% of treated patients. Nonetheless, its underlying neurotoxic mechanism is still not fully elucidated. Therefore, this work aimed to provide a comprehensive review using PubMed as a database to assess the studies published on the field and, therefore, highlight the clinical manifestations of chemobrain and the putative neurotoxicity mechanisms.
In the last two decades, a great number of papers was published on the topic, mainly with clinical observations. Chemotherapy-treated patients showed that the cognitive domains most often impaired were verbal memory, psychomotor function, visual memory, visuospatial and verbal learning, memory function and attention. Chemotherapy alters the brain’s metabolism, white and grey matter and functional connectivity of brain areas. Several mechanisms have been proposed to cause chemobrain but increase of proinflammatory cytokines with oxidative stress seem more relevant, not excluding the action on neurotransmission and cellular death or impaired hippocampal neurogenesis. The interplay between these mechanisms and susceptible factors makes the clinical management of chemobrain even more difficult. New studies, mainly referring to the underlying mechanisms of chemobrain and protective measures, are important in the future, as it is expected that chemobrain will have more clinical impact in the coming years, since the number of cancer survivors is steadily increasing.
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Abbreviations
- 5-FU:
-
5-Fluorouracil
- 3-NT:
-
3-nitrotyrosine
- BBB:
-
Blood-brain barrier
- BDNF:
-
Brain-derived neurotrophic factor
- CNS:
-
Central nervous system
- COX-2:
-
Cyclooxygenase type 2
- CYA:
-
Cyclophosphamide
- DOX:
-
Doxorubicin
- DTI:
-
Diffusion-tensor imaging
- EEG:
-
Electroencephalogram
- EORTC QLQ-C30:
-
European organization for research and treatment of cancer quality of life questionnaire C30
- ERP:
-
Event-related potential
- fMRI:
-
Functional magnetic resonance imaging
- GCEE:
-
γ-glutamyl cysteine ethyl ester
- GFAP:
-
Glial fibrillary acidic protein
- GSH:
-
Glutathione
- HNE:
-
4-hydroxynonenal
- HSCS:
-
High-sensitivity cognitive screen
- iNOS:
-
Inducible nitric oxide synthase
- MMSE:
-
Mini mental state examination
- MRI:
-
Magnetic resonance imaging
- MTX:
-
Methotrexate
- NF-κB:
-
Nuclear factor kappa B
- PET:
-
Positron emission tomography
- RONS:
-
Reactive oxygen and nitrogen species
- ROS:
-
Reactive oxygen species
- TNF-α:
-
Tumor necrosis factor alpha
- VBM:
-
Voxel-based morphometry
References
Adams-Price CE, Morse LW, Cross GW, Williams M, Wells-Parker E (2009) The effects of chemotherapy on Useful Field of View (UFOV) in younger and older breast cancer patients. Exp Aging Res 35(2):220–234. https://doi.org/10.1080/03610730902720497
Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 7(3):192. https://doi.org/10.1038/nrc2073
Ahles TA, Saykin AJ, Furstenberg CT et al (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 20(2):485–493. https://doi.org/10.1200/jco.2002.20.2.485
Ahles TA, Saykin AJ, McDonald BC et al (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 28(29):4434–4440. https://doi.org/10.1200/jco.2009.27.0827
Ahles TA, Saykin AJ, Noll WW et al (2003) The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psychooncology 12(6):612–619. https://doi.org/10.1002/pon.742
Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR, Kleinman JE (2003) Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci 23(6):2008–2013. https://doi.org/10.1523/JNEUROSCI.23-06-02008.2003
Alexander TC, Kiffer F, Groves T et al (2018) Effects of thioTEPA chemotherapy on cognition and motor coordination. Synapse. https://doi.org/10.1002/syn.22085
Alharbi I, Alharbi H, Almogbel Y, Alalwan A, Alhowail A (2020) Effect of Metformin on Doxorubicin-Induced Memory Dysfunction. Brain Sci 10(3) https://doi.org/10.3390/brainsci10030152
Alhowail AH, Chigurupati S, Sajid S, Mani V (2019) Ameliorative effect of metformin on cyclophosphamide-induced memory impairment in mice. Eur Rev Med Pharmacol Sci 23(21):9660–9666. https://doi.org/10.26355/eurrev_201911_19460
Ali MA, Menze ET, Tadros MG, Tolba MF (2020) Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: Emphasis on the modulation of oxidative stress and neuroinflammation. Neuropharmacology 181:108334. https://doi.org/10.1016/j.neuropharm.2020.108334
Allen BD, Apodaca LA, Syage AR et al (2019) Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments. Acta Neuropathol Commun 7(1):186. https://doi.org/10.1186/s40478-019-0838-8
Almeida D, Pinho R, Correia V, et al. (2018) Mitoxantrone is More Toxic than Doxorubicin in SH-SY5Y Human Cells: A 'Chemobrain' In Vitro Study. Pharmaceuticals (Basel) 11(2) doi:https://doi.org/10.3390/ph11020041
Aluise CD, Miriyala S, Noel T et al (2011) 2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-α release: implications for the reactive oxygen species-mediated mechanisms of chemobrain. Free Radic Biol Med 50(11):1630–1638. https://doi.org/10.1016/j.freeradbiomed.2011.03.009
Aluise CD, St Clair D, Vore M, Butterfield DA (2009) In vivo amelioration of adriamycin induced oxidative stress in plasma by gamma-glutamylcysteine ethyl ester (GCEE). Cancer Lett 282(1):25–29. https://doi.org/10.1016/j.canlet.2009.02.047
Amidi A, Agerbaek M, Wu LM et al (2017) Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment. Brain Imaging Behav 11(3):769–783. https://doi.org/10.1007/s11682-016-9552-3
Amidi A, Wu LM, Pedersen AD et al (2015) Cognitive impairment in testicular cancer survivors 2–7 years after treatment. Support Care Cancer 23(10):2973–2979. https://doi.org/10.1007/s00520-015-2663-3
Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10(7):S18–S25. https://doi.org/10.1038/nrn1434
Anderson DE, Kedar S, Bhatt VR, Schmid K, Holstein SA, Rizzo M (2020) Neurophysiologic and ophthalmic markers of chemotherapy-related cognitive impairment in patients diagnosed with hematologic cancer: a feasibility study. J Neurol Sci 410:116644. https://doi.org/10.1016/j.jns.2019.116644
Ando-Tanabe N, Iwamitsu Y, Kuranami M et al (2014) Cognitive function in women with breast cancer receiving adjuvant chemotherapy and healthy controls. Breast Cancer 21(4):453–462. https://doi.org/10.1007/s12282-012-0405-7
Andreis F, Ferri M, Mazzocchi M et al (2013) Lack of a chemobrain effect for adjuvant FOLFOX chemotherapy in colon cancer patients. A Pilot Study. Support Care Cancer 21(2):583–590. https://doi.org/10.1007/s00520-012-1560-2
Andres AL, Gong X, Di K, Bota DA (2014) Low-doses of cisplatin injure hippocampal synapses: a mechanism for “chemo” brain? Exp Neurol 255:137–144. https://doi.org/10.1016/j.expneurol.2014.02.020
Antkiewicz-Michaluk L, Krzemieniecki K, Romanska I, Michaluk J, Krygowska-Wajs A (2016) Acute treatment with doxorubicin induced neurochemical impairment of the function of dopamine system in rat brain structures. Pharmacol Rep 68(3):627–630. https://doi.org/10.1016/j.pharep.2016.01.009
Arndt V, Koch-Gallenkamp L, Jansen L et al (2017) Quality of life in long-term and very long-term cancer survivors versus population controls in Germany. Acta Oncol 56(2):190–197
Askren MK, Jung M, Berman MG et al (2014) Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation. Breast Cancer Res Treat 147(2):445–455. https://doi.org/10.1007/s10549-014-3092-6
Ayala-Feliciano M, Pons-Valerio JJ, Pons-Madera J, Acevedo SF (2011) The relationship between visuospatial memory and coping strategies in breast cancer survivors. Breast Cancer (auckl) 5:117–130. https://doi.org/10.4137/bcbcr.s6957
Aziz NM (2002) Cancer survivorship research: challenge and opportunity. J Nutr 132(11):3494S–3503S. https://doi.org/10.1093/jn/132.11.3494S
Bagnall-Moreau C, Chaudhry S, Salas-Ramirez K, Ahles T, Hubbard K (2019) Chemotherapy-induced cognitive impairment is associated with increased inflammation and oxidative damage in the hippocampus. Mol Neurobiol 56(10):7159–7172. https://doi.org/10.1007/s12035-019-1589-z
Barbosa DJ, Capela JP, de Lourdes BM, Carvalho F (2015) In vitro models for neurotoxicology research. Toxicology Research 4(4):801–842. https://doi.org/10.1039/C4TX00043A
Barkoukis TJ (2012) Sleep-Related Medical Disorders. In: Blumer J (ed) Therapy in Sleep Medicine. 1st edn. Elsevier/Saunders, p 607–615
Baudino B, D’Agata F, Caroppo P et al (2012) The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients. Q J Nucl Med Mol Imaging 56(6):559–568
Baxter MF, Dulworth AN, Smith TM (2011) Identification of mild cognitive impairments in cancer survivors. Occup Ther Health Care 25(1):26–37. https://doi.org/10.3109/07380577.2010.533251
Becker H, Henneghan A, Mikan SQ (2015) When do I get my brain back? Breast cancer survivors’ experiences of cognitive problems. Clin J Oncol Nurs 19(2):180–184. https://doi.org/10.1188/15.cjon.180-184
Bender CM, Sereika SM, Berga SL et al (2006) Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncology 15(5):422–430. https://doi.org/10.1002/pon.964
Bhowmik A, Khan R, Ghosh MK (2015) Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int 2015:320941. https://doi.org/10.1155/2015/320941
Biglia N, Bounous VE, Malabaila A et al (2012) Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study. Eur J Cancer Care (engl) 21(4):485–492. https://doi.org/10.1111/j.1365-2354.2011.01320.x
Blommaert J, Schroyen G, Vandenbulcke M et al (2019) Age-dependent brain volume and neuropsychological changes after chemotherapy in breast cancer patients. Hum Brain Mapp 40(17):4994–5010. https://doi.org/10.1002/hbm.24753
Bourke RS, West CR, Chheda G, Tower DB (1973) Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res 33(7):1735–1746
Branca JJV, Maresca M, Morucci G et al (2018) Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity. Oncotarget 9(34):23426–23438. https://doi.org/10.18632/oncotarget.25193
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF (2000) Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 18(14):2695–2701. https://doi.org/10.1200/jco.2000.18.14.2695
Briones TL, Woods J (2014) Dysregulation in myelination mediated by persistent neuroinflammation: possible mechanisms in chemotherapy-related cognitive impairment. Brain Behav Immun 35:23–32. https://doi.org/10.1016/j.bbi.2013.07.175
Bruno J, Hosseini SM, Kesler S (2012) Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors. Neurobiol Dis 48(3):329–338. https://doi.org/10.1016/j.nbd.2012.07.009
Calvio L, Peugeot M, Bruns GL, Todd BL, Feuerstein M (2010) Measures of cognitive function and work in occupationally active breast cancer survivors. J Occup Environ Med 52(2):219–227. https://doi.org/10.1097/JOM.0b013e3181d0bef7
Cardoso CV, de Barros MP, Bachi ALL et al (2020) Chemobrain in rats: Behavioral, morphological, oxidative and inflammatory effects of doxorubicin administration. Behavioural Brain Res 378:112233. https://doi.org/10.1016/j.bbr.2019.112233
Carreira H, Williams R, Dempsey H, Stanway S, Smeeth L, Bhaskaran K (2020) Quality of life and mental health in breast cancer survivors compared with non-cancer controls: a study of patient-reported outcomes in the United Kingdom. J Cancer Surviv. https://doi.org/10.1007/s11764-020-00950-3
Carroll JE, Van Dyk K, Bower JE et al (2019) Cognitive performance in survivors of breast cancer and markers of biological aging. Cancer 125(2):298–306. https://doi.org/10.1002/cncr.31777
Castellon S, Ganz PA (2009) Neuropsychological studies in breast cancer: in search of chemobrain. Breast Cancer Res Treat 116(1):125–127. https://doi.org/10.1007/s10549-008-0211-2
Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA (2004) Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol 26(7):955–969. https://doi.org/10.1080/13803390490510905
Cerulla N, Arcusa A, Navarro JB et al (2019) Cognitive impairment following chemotherapy for breast cancer: The impact of practice effect on results. J Clin Exp Neuropsychol 41(3):290–299. https://doi.org/10.1080/13803395.2018.1546381
Cerulla N, Arcusa A, Navarro JB et al (2017) Role of taxanes in chemotherapy-related cognitive impairment: a prospective longitudinal study. Breast Cancer Res Treat 164(1):179–187. https://doi.org/10.1007/s10549-017-4240-6
Chen BT, Jin T, Patel SK et al (2018) Gray matter density reduction associated with adjuvant chemotherapy in older women with breast cancer. Breast Cancer Res Treat 172(2):363–370. https://doi.org/10.1007/s10549-018-4911-y
Chen BT, Ye N, Wong CW et al (2019) Effects of chemotherapy on aging white matter microstructure: a longitudinal diffusion tensor imaging study. J Geriatr Oncol. https://doi.org/10.1016/j.jgo.2019.09.016
Chen BT, Ye N, Wong CW et al (2020a) Effects of chemotherapy on aging white matter microstructure: a longitudinal diffusion tensor imaging study. J Geriatr Oncol 11(2):290–296. https://doi.org/10.1016/j.jgo.2019.09.016
Chen VC, Lin KY, Tsai YH, Weng JC (2020b) Connectome analysis of brain functional network alterations in breast cancer survivors with and without chemotherapy. PLoS ONE 15(5):e0232548. https://doi.org/10.1371/journal.pone.0232548
Chen X, Li J, Ren J et al (2014) Selective impairment of attention networks in breast cancer patients receiving chemotherapy treatment. Psychooncology 23(10):1165–1171. https://doi.org/10.1002/pon.3539
Chen Y, Jungsuwadee P, Vore M, Butterfield DA, St Clair DK (2007) Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interventions 7(3):147. https://doi.org/10.1124/mi.7.3.6
Cheng H, Li W, Gong L et al (2017) Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors. Sci Rep 7:45135. https://doi.org/10.1038/srep45135
Cheng H, Yang Z, Dong B et al (2013) Chemotherapy-induced prospective memory impairment in patients with breast cancer. Psychooncology 22(10):2391–2395. https://doi.org/10.1002/pon.3291
Cheung YT, Ng T, Shwe M et al (2015) Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study. Ann Oncol 26(7):1446–1451. https://doi.org/10.1093/annonc/mdv206
Chiu GS, Maj MA, Rizvi S et al (2017) Pifithrin-mu Prevents cisplatin-induced chemobrain by preserving neuronal mitochondrial function. Cancer Res 77(3):742–752. https://doi.org/10.1158/0008-5472.can-16-1817
Choi SM, Lee SH, Yang YS, Kim BC, Kim MK, Cho KH (2001) 5-fluorouracil-induced leukoencephalopathy in patients with breast cancer. J Korean Med Sci 16(3):328–334. https://doi.org/10.3346/jkms.2001.16.3.328
Christie LA, Acharya MM, Parihar VK, Nguyen A, Martirosian V, Limoli CL (2012) Impaired cognitive function and hippocampal neurogenesis following cancer chemotherapy. Clin Cancer Res 18(7):1954–1965. https://doi.org/10.1158/1078-0432.ccr-11-2000
Collins B, MacKenzie J, Tasca GA, Scherling C, Smith A (2013) Cognitive effects of chemotherapy in breast cancer patients: a dose-response study. Psychooncology 22(7):1517–1527. https://doi.org/10.1002/pon.3163
Collins B, Mackenzie J, Tasca GA, Scherling C, Smith A (2014) Persistent cognitive changes in breast cancer patients 1 year following completion of chemotherapy. J Int Neuropsychol Soc 20(4):370–379. https://doi.org/10.1017/s1355617713001215
Colonna M, Butovsky O (2017) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 35:441–468. https://doi.org/10.1146/annurev-immunol-051116-052358
Conklin KA (2004) Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther 3(4):294–300. https://doi.org/10.1177/1534735404270335
Conroy T, Paillot B, Francois E et al (2005) Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer–a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol 23(6):1228–1236. https://doi.org/10.1200/jco.2005.06.050
Correa DD, Root JC, Kryza-Lacombe M et al (2017) Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study. Brain Imaging Behav 11(6):1652–1663. https://doi.org/10.1007/s11682-016-9608-4
Correa DD, Zhou Q, Thaler HT, Maziarz M, Hurley K, Hensley ML (2010) Cognitive functions in long-term survivors of ovarian cancer. Gynecol Oncol 119(2):366–369. https://doi.org/10.1016/j.ygyno.2010.06.023
Cruzado JA, Lopez-Santiago S, Martinez-Marin V, Jose-Moreno G, Custodio AB, Feliu J (2014) Longitudinal study of cognitive dysfunctions induced by adjuvant chemotherapy in colon cancer patients. Support Care Cancer 22(7):1815–1823. https://doi.org/10.1007/s00520-014-2147-x
Cull A, Hay C, Love SB, Mackie M, Smets E, Stewart M (1996) What do cancer patients mean when they complain of concentration and memory problems? Br J Cancer 74(10):1674–1679
Czerska M, Mikolajewska K, Zielinski M, Gromadzinska J, Wasowicz W (2015) Today’s oxidative stress markers. Med Pr 66(3):393–405. https://doi.org/10.13075/mp.5893.00137
da Ros M, Iorio AL, Lucchesi M, Stival A, de Martino M, Sardi I (2015) The Use of Anthracyclines for Therapy of CNS Tumors. Anticancer Agents Med Chem 15(6):721–727. https://doi.org/10.2174/1871520615666150407155319
Davis BD, Fernandez F, Adams F, et al. (1987) Diagnosis of dementia in cancer patients. Cognitive impairment in these patients can go unrecognized. Psychosomatics 28(4):175–9 https://doi.org/10.1016/s0033-3182(87)72542-0
de Boer AG (2014) The European cancer and work network: CANWON. J Occup Rehabil 24(3):393–398. https://doi.org/10.1007/s10926-013-9474-5
de Jonge ME, Huitema AD, Rodenhuis S, Beijnen JH (2005) Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinetics 44(11):1135–1164. https://doi.org/10.2165/00003088-200544110-00003
de Ruiter MB, Reneman L, Boogerd W et al (2012) Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Hum Brain Mapp 33(12):2971–2983. https://doi.org/10.1002/hbm.21422
de Ruiter MB, Reneman L, Boogerd W et al (2011) Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp 32(8):1206–1219. https://doi.org/10.1002/hbm.21102
de Vries NA, Beijnen JH, Boogerd W, van Tellingen O (2006) Blood-brain barrier and chemotherapeutic treatment of brain tumors. Expert Rev Neurother 6(8):1199–1209. https://doi.org/10.1586/14737175.6.8.1199
Debess J, Riis JO, Engebjerg MC, Ewertz M (2010) Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study. Breast Cancer Res Treat 121(1):91–100. https://doi.org/10.1007/s10549-010-0756-8
Deprez S, Amant F, Smeets A et al (2012) Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol 30(3):274–281. https://doi.org/10.1200/jco.2011.36.8571
Deprez S, Amant F, Yigit R et al (2011) Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum Brain Mapp 32(3):480–493. https://doi.org/10.1002/hbm.21033
Deprez S, Billiet T, Sunaert S, Leemans A (2013) Diffusion tensor MRI of chemotherapy-induced cognitive impairment in non-CNS cancer patients: a review. Brain Imaging Behav 7(4):409–435. https://doi.org/10.1007/s11682-012-9220-1
Deprez S, Vandenbulcke M, Peeters R et al (2014) Longitudinal assessment of chemotherapy-induced alterations in brain activation during multitasking and its relation with cognitive complaints. J Clin Oncol 32(19):2031–2038. https://doi.org/10.1200/jco.2013.53.6219
Dietrich J, Han R, Yang Y, Mayer-Proschel M, Noble M (2006) CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol 5(7):22. https://doi.org/10.1186/jbiol50
Donovan KA, Small BJ, Andrykowski MA, Schmitt FA, Munster P, Jacobsen PB (2005) Cognitive functioning after adjuvant chemotherapy and/or radiotherapy for early-stage breast carcinoma. Cancer 104(11):2499–2507. https://doi.org/10.1002/cncr.21482
Dose J, Huebbe P, Nebel A, Rimbach G (2016) APOE genotype and stress response-a mini review. Lipids Health Dis 15(1):121. https://doi.org/10.1186/s12944-016-0288-2
Du XL, Xia R, Hardy D (2010) Relationship between chemotherapy use and cognitive impairments in older women with breast cancer: findings from a large population-based cohort. Am J Clin Oncol 33(6):533–543. https://doi.org/10.1097/COC.0b013e3181b9cf1b
Duijts SF, van der Beek AJ, Boelhouwer IG, Schagen SB (2017) Cancer-related cognitive impairment and patients’ ability to work: a current perspective. Curr Opin Support Palliat Care 11(1):19–23. https://doi.org/10.1097/spc.0000000000000248
Dumas JA, Makarewicz J, Schaubhut GJ et al (2013) Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study. Brain Imaging Behav 7(4):524–532. https://doi.org/10.1007/s11682-013-9244-1
Eberhardt B, Dilger S, Musial F, Wedding U, Weiss T, Miltner WH (2006) Medium-term effects of chemotherapy in older cancer patients. Support Care Cancer 14(3):216–222. https://doi.org/10.1007/s00520-005-0894-4
Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ (2004) Estrogen- and tamoxifen-associated effects on brain structure and function. Neuroimage 21(1):364–371. https://doi.org/10.1016/j.neuroimage.2003.08.037
Edwards BJ, Zhang X, Sun M et al (2018) Neurocognitive deficits in older patients with cancer. J Geriatr Oncol 9(5):482–487. https://doi.org/10.1016/j.jgo.2018.02.010
Egorin MJ, Kaplan RS, Salcman M et al (1982) Cyclophosphamide plasma and cerebrospinal fluid kinetics with and without dimethyl sulfoxide. Clin Pharmacol Therapeutics 32(1):122–128
Ehrenstein JK, van Zon SKR, Duijts SFA et al (2020) Type of cancer treatment and cognitive symptoms in working cancer survivors: an 18-month follow-up study. J Cancer Surviv 14(2):158–167. https://doi.org/10.1007/s11764-019-00839-w
El-Agamy SE, Abdel-Aziz AK, Esmat A, Azab SS (2019) Chemotherapy and cognition: comprehensive review on doxorubicin-induced chemobrain. Cancer Chemother Pharmacol 84(1):1–14. https://doi.org/10.1007/s00280-019-03827-0
El-Agamy SE, Abdel-Aziz AK, Wahdan S, Esmat A, Azab SS (2018) Astaxanthin ameliorates doxorubicin-induced cognitive impairment (Chemobrain) in experimental rat model: impact on oxidative, inflammatory, and apoptotic machineries. Mol Neurobiol 55(7):5727–5740. https://doi.org/10.1007/s12035-017-0797-7
El M, Mustafa S, Umka J et al (2012) The effect of 5-fluorouracil on the long term survival and proliferation of cells in the rat hippocampus. Brain Res Bull 88(5):514–518. https://doi.org/10.1016/j.brainresbull.2012.05.005
Fan HG, Houede-Tchen N, Yi QL et al (2005) Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study. J Clin Oncol 23(31):8025–8032. https://doi.org/10.1200/jco.2005.01.6550
Fan HG, Park A, Xu W et al (2009) The influence of erythropoietin on cognitive function in women following chemotherapy for breast cancer. Psychooncology 18(2):156–161. https://doi.org/10.1002/pon.1372
Feng Y, Wang YF, Zheng LJ, Shi Z, Huang W, Zhang LJ (2020) Network-level functional connectivity alterations in chemotherapy treated breast cancer patients: a longitudinal resting state functional MRI study. Cancer Imaging 20(1):73. https://doi.org/10.1186/s40644-020-00355-6
Fitzmaurice C, Abate D, Abbasi N et al (2019) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncol 5(12):1749–1768. https://doi.org/10.1001/jamaoncol.2019.2996
Folstein MF, Fetting JH, Lobo A, Niaz U, Capozzoli KD (1984) Cognitive assessment of cancer patients. Cancer 53(10 Suppl):2250–2257
Freeman JR, Broshek DK (2002) Assessing cognitive dysfunction in breast cancer: what are the tools? Clin Breast Cancer 3(Suppl 3):S91–S99
Gaillard PJ, Appeldoorn CC, Dorland R et al (2014) Pharmacokinetics, brain delivery, and efficacy in brain tumor-bearing mice of glutathione pegylated liposomal doxorubicin (2B3–101). PloS one 9(1):e82331. https://doi.org/10.1371/journal.pone.0082331
Gallego Perez-Larraya J, Hildebrand J (2014) Brain metastases. Handbook Clin Neurol 121:1143–1157. https://doi.org/10.1016/b978-0-7020-4088-7.00077-8
Gandhi S, Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012: https://doi.org/10.1155/2012/428010
Garthe A, Kempermann G (2013) An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis. Front Neurosci 7:63. https://doi.org/10.3389/fnins.2013.00063
Gerstenecker A, Nabors LB, Meneses K et al (2014) Cognition in patients with newly diagnosed brain metastasis: profiles and implications. J Neuro-Oncol 120(1):179–185. https://doi.org/10.1007/s11060-014-1543-x
Gibson EM, Nagaraja S, Ocampo A et al (2019) Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment. Cell 176(1–2):43-55.e13. https://doi.org/10.1016/j.cell.2018.10.049
Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221(1):3–12. https://doi.org/10.1002/path.2697
Gopal KV, Wu C, Shrestha B, Campbell KC, Moore EJ, Gross GW (2012) d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks. Neurotoxicol Teratol 34(5):495–504. https://doi.org/10.1016/j.ntt.2012.06.002
Graul EH, Schaumloffel E, Hundeshagen H, Wilmanns H, Simon G (1967) Metabolism of radioactive cyclophosphamide Animal tests and clinical studies. Cancer 20(5):896–899. https://doi.org/10.1002/1097-0142(1967)20:5%3c896::aid-cncr2820200551%3e3.0.co;2-d
Greimel ER, Bjelic-Radisic V, Pfisterer J, Hilpert F, Daghofer F, du Bois A (2006) Randomized study of the arbeitsgemeinschaft gynaekologische onkologie ovarian cancer study group comparing quality of life in patients with ovarian cancer treated with cisplatin/paclitaxel versus carboplatin/paclitaxel. J Clin Oncol 24(4):579–586. https://doi.org/10.1200/jco.2005.02.4067
Grisold W, Grisold A, Löscher W (2017) Cancer therapy and neuromuscular complications: a mini review. Neurology (ECronicon) 9(1):20–26
Guest PC (2020) MK-801 treatment of oligodendrocytes as a cellular model of aging. Methods Mol Biol (clifton, NJ) 2138:431–447. https://doi.org/10.1007/978-1-0716-0471-7_32
Gutmann DH (2019) Clearing the Fog surrounding Chemobrain. Cell 176(1–2):2–4. https://doi.org/10.1016/j.cell.2018.12.027
Harry GJ, Kraft AD (2008) Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol 4(10):1265–1277. https://doi.org/10.1517/17425255.4.10.1265
Hartung H-P, Gonsette R, Konig N et al (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360(9350):2018–2025. https://doi.org/10.1016/S0140-6736(02)12023-X
Heck JE, Albert SM, Franco R, Gorin SS (2008) Patterns of dementia diagnosis in surveillance, epidemiology, and end results breast cancer survivors who use chemotherapy. J Am Geriatr Soc 56(9):1687–1692. https://doi.org/10.1111/j.1532-5415.2008.01848.x
Heflin LH, Meyerowitz BE, Hall P et al (2005) Cancer as a risk factor for long-term cognitive deficits and dementia. J Natl Cancer Inst 97(11):854–856. https://doi.org/10.1093/jnci/dji137
Henneghan A, Rao V, Harrison RA et al (2020) Cortical brain age from pre-treatment to post-chemotherapy in patients with breast cancer. Neurotox Res 37(4):788–799. https://doi.org/10.1007/s12640-019-00158-z
Hermelink K (2011) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 117(5):1103; author reply 1103–4 doi:https://doi.org/10.1002/cncr.25708
Hermelink K, Kuchenhoff H, Untch M et al (2010) Two different sides of “chemobrain”: determinants and nondeterminants of self-perceived cognitive dysfunction in a prospective, randomized, multicenter study. Psychooncology 19(12):1321–1328. https://doi.org/10.1002/pon.1695
Hess LM, Chambers SK, Hatch K et al (2010) Pilot study of the prospective identification of changes in cognitive function during chemotherapy treatment for advanced ovarian cancer. J Support Oncol 8(6):252–258. https://doi.org/10.3816/cbc.2002.s.019
Hess LM, Huang HQ, Hanlon AL et al (2015) Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study. Gynecol Oncol 139(3):541–545. https://doi.org/10.1016/j.ygyno.2015.10.003
Hosseini SM, Koovakkattu D, Kesler SR (2012) Altered small-world properties of gray matter networks in breast cancer. BMC Neurol 12:28. https://doi.org/10.1186/1471-2377-12-28
Huo X, Reyes TM, Heijnen CJ, Kavelaars A (2018) Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice. Sci Rep 8(1):17400. https://doi.org/10.1038/s41598-018-35919-x
Hurria A, Goldfarb S, Rosen C et al (2006a) Effect of adjuvant breast cancer chemotherapy on cognitive function from the older patient’s perspective. Breast Cancer Res Treat 98(3):343–348. https://doi.org/10.1007/s10549-006-9171-6
Hurria A, Rosen C, Hudis C et al (2006b) Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc 54(6):925–931. https://doi.org/10.1111/j.1532-5415.2006.00732.x
Iconomou G, Koutras A, Karaivazoglou K et al (2008) Effect of epoetin alpha therapy on cognitive function in anaemic patients with solid tumours undergoing chemotherapy. Eur J Cancer Care (engl) 17(6):535–541. https://doi.org/10.1111/j.1365-2354.2007.00857.x
Jacobs S, McCully C, Murphy R, Bacher J, Balis F, Fox E (2009) Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates. Cancer Chemotherapy Pharmacol 65:817–824. https://doi.org/10.1007/s00280-009-1085-7
Jacobs S, McCully CL, Murphy RF, Bacher J, Balis FM, Fox E (2010) Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates. Cancer Chemotherapy Pharmacol 65(5):817–824. https://doi.org/10.1007/s00280-009-1085-7
Janelsins MC, Heckler CE, Thompson BD, Gross RA, Opanashuk LA, Cory-Slechta DA (2016) A clinically relevant dose of cyclophosphamide chemotherapy impairs memory performance on the delayed spatial alternation task that is sustained over time as mice age. Neurotoxicology 56:287–293. https://doi.org/10.1016/j.neuro.2016.06.013
Janelsins MC, Roscoe JA, Berg MJ et al (2010) IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice. Cancer Invest 28(5):544–553. https://doi.org/10.3109/07357900903405942
Jansen C, Miaskowski C, Dodd M, Dowling G, Kramer J (2005) Potential mechanisms for chemotherapy-induced impairments in cognitive function. Oncol Nurs Forum 32(6):1151–1163. https://doi.org/10.1188/05.onf.1151-1163
Jansen CE, Cooper BA, Dodd MJ, Miaskowski CA (2011) A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Support Care Cancer 19(10):1647–1656. https://doi.org/10.1007/s00520-010-0997-4
Jansen CE, Dodd MJ, Miaskowski CA, Dowling GA, Kramer J (2008) Preliminary results of a longitudinal study of changes in cognitive function in breast cancer patients undergoing chemotherapy with doxorubicin and cyclophosphamide. Psychooncology 17(12):1189–1195. https://doi.org/10.1002/pon.1342
Jansen CE, Miaskowski CA, Dodd MJ, Dowling GA (2007) A meta-analysis of the sensitivity of various neuropsychological tests used to detect chemotherapy-induced cognitive impairment in patients with breast cancer. Oncol Nurs Forum 34(5):997–1005. https://doi.org/10.1188/07.onf.997-1005
Jarmolowicz DP, Gehringer R, Lemley SM, Sofis MJ, Kaplan S, Johnson MA (2019) 5-Fluorouracil impairs attention and dopamine release in rats. Behav Brain Res 362:319–322. https://doi.org/10.1016/j.bbr.2019.01.007
Jenkins V, Shilling V, Deutsch G et al (2006) A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 94(6):828–834. https://doi.org/10.1038/sj.bjc.6603029
Jim HS, Donovan KA, Small BJ, Andrykowski MA, Munster PN, Jacobsen PB (2009) Cognitive functioning in breast cancer survivors: a controlled comparison. Cancer 115(8):1776–1783. https://doi.org/10.1002/cncr.24192
Joly F, Espie M, Marty M, Heron JF, Henry-Amar M (2000) Long-term quality of life in premenopausal women with node-negative localized breast cancer treated with or without adjuvant chemotherapy. Br J Cancer 83(5):577–582. https://doi.org/10.1054/bjoc.2000.1337
Joshi G, Hardas S, Sultana R, St Clair DK, Vore M, Butterfield DA (2007) Glutathione elevation by gamma-glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implication for chemobrain. J Neurosci Res 85(3):497–503. https://doi.org/10.1002/jnr.21158
Jung MS, Cimprich B (2014) Cognitive deficits in Korean women treated with chemotherapy for breast cancer. Cancer Nurs 37(3):E31-42. https://doi.org/10.1097/NCC.0b013e3182980383
Jung MS, Zhang M, Askren MK et al (2017) Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis. Brain Imaging Behav 11(1):86–97. https://doi.org/10.1007/s11682-016-9507-8
Kardan O, Reuter-Lorenz PA, Peltier S et al (2019) Brain connectivity tracks effects of chemotherapy separately from behavioral measures. Neuroimage Clin 21:101654. https://doi.org/10.1016/j.nicl.2019.101654
Kassmann CM, Lappe-Siefke C, Baes M et al (2007) Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes. Nat Genet 39(8):969–976. https://doi.org/10.1038/ng2070
Keeney JTR, Ren X, Warrier G et al (2018) Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”). Oncotarget 9(54):30324–30339. https://doi.org/10.18632/oncotarget.25718
Kesler S, Janelsins M, Koovakkattu D et al (2013a) Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav Immun 30(Suppl):S109–S116. https://doi.org/10.1016/j.bbi.2012.05.017
Kesler SR, Wefel JS, Hosseini SM, Cheung M, Watson CL, Hoeft F (2013b) Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls. Proc Natl Acad Sci USA 110(28):11600–11605. https://doi.org/10.1073/pnas.1214551110
Kesler SR, Blayney DW (2016) Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors. JAMA Oncol 2(2):185–192. https://doi.org/10.1001/jamaoncol.2015.4333
Kettenmann H, Verkhratsky A (2013) Glial cells. Neuroscience in the 21st Century: From Basic to Clinical:475–506
Khan HA, Khan I, Lee Y-k (2018) Role of immune factors in bioavailability and toxicity of carbon nanomaterials Fullerens, Graphenes and Nanotubes. Elsevier, p 601–630
Khan OF, Cusano E, Raissouni S et al (2019) Immediate-term cognitive impairment following intravenous (IV) chemotherapy: a prospective pre-post design study. BMC Cancer 19(1):150. https://doi.org/10.1186/s12885-019-5349-2
Kim HG, Shin NY, Bak Y et al (2017) Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: a preliminary study. Eur Radiol 27(7):2679–2688. https://doi.org/10.1007/s00330-016-4578-x
Kim YA, Chung HC, Choi HJ, Rha SY, Seong JS, Jeung HC (2006) Intermediate dose 5-fluorouracil-induced encephalopathy. Jpn J Clin Oncol 36(1):55–59. https://doi.org/10.1093/jjco/hyi214
Kitamura Y, Hattori S, Yoneda S et al (2015) Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation. Behav Brain Res 292:184–193. https://doi.org/10.1016/j.bbr.2015.06.007
Kohli S, Fisher SG, Tra Y et al (2009) The effect of modafinil on cognitive function in breast cancer survivors. Cancer 115(12):2605–2616. https://doi.org/10.1002/cncr.24287
Koll TT, Sheese AN, Semin J et al (2020) Screening for cognitive impairment in older adults with hematological malignancies using the montreal cognitive assessment and neuropsychological testing. J Geriatr Oncol 11(2):297–303. https://doi.org/10.1016/j.jgo.2019.11.007
Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB (2012a) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30(10):1080–1086. https://doi.org/10.1200/jco.2011.37.0189
Koppelmans V, de Ruiter MB, van der Lijn F et al (2012b) Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy. Breast Cancer Res Treat 132(3):1099–1106. https://doi.org/10.1007/s10549-011-1888-1
Kovalchuk A, Ilnytskyy Y, Rodriguez-Juarez R et al (2017) Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice. Oncotarget 8(51):88276–88293. https://doi.org/10.18632/oncotarget.19835
Kreukels BP, Schagen SB, Ridderinkhof KR et al (2006) Effects of high-dose and conventional-dose adjuvant chemotherapy on long-term cognitive sequelae in patients with breast cancer: an electrophysiologic study. Clin Breast Cancer 7(1):67–78. https://doi.org/10.3816/CBC.2006.n.015
Kreukels BP, Schagen SB, Ridderinkhof KR, Boogerd W, Hamburger HL, van Dam FS (2005) Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy. Breast Cancer Res Treat 94(1):53–61. https://doi.org/10.1007/s10549-005-7093-3
Kurita K, Meyerowitz BE, Hall P, Gatz M (2011) Long-term cognitive impairment in older adult twins discordant for gynecologic cancer treatment. J Gerontol A Biol Sci Med Sci 66(12):1343–1349. https://doi.org/10.1093/gerona/glr140
Kwatra M, Jangra A, Mishra M et al (2016) Naringin and sertraline ameliorate doxorubicin-induced behavioral deficits through modulation of serotonin level and mitochondrial complexes protection pathway in rat hippocampus. Neurochem Res 41(9):2352–2366. https://doi.org/10.1007/s11064-016-1949-2
Kwon KA, Kwon HC, Kim MC et al (2010) A case of 5-fluorouracil induced encephalopathy. Cancer Res Treat 42(2):118–120. https://doi.org/10.4143/crt.2010.42.2.118
Lange M, Heutte N, Rigal O et al (2016) Decline in cognitive function in older adults with early-stage breast cancer after adjuvant treatment. Oncologist 21(11):1337–1348. https://doi.org/10.1634/theoncologist.2016-0014
Lepage C, Smith AM, Moreau J et al (2014) A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients. Springerplus 3:444. https://doi.org/10.1186/2193-1801-3-444
Levine PM, Silberfarb PM, Lipowski Z (1978) Mental disorders in cancer patients. A study of 100 psychiatric referrals. Cancer 42(3):1385–1391
Li TY, Chen VC, Yeh DC et al (2018a) Investigation of chemotherapy-induced brain structural alterations in breast cancer patients with generalized q-sampling MRI and graph theoretical analysis. BMC Cancer 18(1):1211. https://doi.org/10.1186/s12885-018-5113-z
Li X, Chen H, Lv Y et al (2018b) Diminished gray matter density mediates chemotherapy dosage-related cognitive impairment in breast cancer patients. Sci Rep 8(1):13801. https://doi.org/10.1038/s41598-018-32257-w
Libert Y, Dubruille S, Borghgraef C et al (2016) Vulnerabilities in older patients when cancer treatment is initiated: does a cognitive impairment impact the two-year survival? PLoS ONE 11(8):e0159734. https://doi.org/10.1371/journal.pone.0159734
Liedke PE, Reolon GK, Kilpp B, Brunetto AL, Roesler R, Schwartsmann G (2009) Systemic administration of doxorubicin impairs aversively motivated memory in rats. Pharmacol Biochem Behav 94(2):239–243. https://doi.org/10.1016/j.pbb.2009.09.001
Linden DE (2005) The p300: where in the brain is it produced and what does it tell us? Neuroscientist 11(6):563–576. https://doi.org/10.1177/1073858405280524
Lomeli N, Di K, Czerniawski J, Guzowski JF, Bota DA (2017) Cisplatin-induced mitochondrial dysfunction is associated with impaired cognitive function in rats. Free Radic Biol Med 102:274–286. https://doi.org/10.1016/j.freeradbiomed.2016.11.046
Long JM, Lee GD, Kelley-Bell B et al (2011) Preserved learning and memory following 5-fluorouracil and cyclophosphamide treatment in rats. Pharmacol Biochem Behav 100(1):205–211. https://doi.org/10.1016/j.pbb.2011.08.012
Lopes MÂ, Meisel A, Carvalho F, Bastos ML (2011) Neuronal nitric oxide synthase is a key factor in doxorubicin-induced toxicity to rat-isolated cortical neurons. Neurotoxicity Res 19(1):14–22. https://doi.org/10.1007/s12640-009-9135-9
Lopes MÂ, Meisel A, Dirnagl U, Carvalho F, Bastos ML (2008) Doxorubicin induces biphasic neurotoxicity to rat cortical neurons. Neurotoxicology 29(2):286–293. https://doi.org/10.1016/j.neuro.2007.12.003
Lopez Zunini RA, Scherling C, Wallis N et al (2013) Differences in verbal memory retrieval in breast cancer chemotherapy patients compared to healthy controls: a prospective fMRI study. Brain Imaging Behav 7(4):460–477. https://doi.org/10.1007/s11682-012-9213-0
Löscher W, Potschka H (2005) Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2(1):86–98. https://doi.org/10.1602/neurorx.2.1.86
Luqmani Y (2005) Mechanisms of drug resistance in cancer chemotherapy. Med Principles Pract 14(Suppl. 1):35–48. https://doi.org/10.1159/000086183
Lyon DE, Cohen R, Chen H et al (2016) Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer. J Neuroimmunol 301:74–82. https://doi.org/10.1016/j.jneuroim.2016.11.002
Lyons L, Elbeltagy M, Bennett G, Wigmore P (2011) The effects of cyclophosphamide on hippocampal cell proliferation and spatial working memory in rat. PLoS ONE 6(6):e21445. https://doi.org/10.1371/journal.pone.0021445
Lyons L, ElBeltagy M, Bennett G, Wigmore P (2012) Fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery. PLoS ONE 7(1):e30010. https://doi.org/10.1371/journal.pone.0030010
Maiese K (2019) Neurotransmissão. In. Accessed 22–01–2021
Mar Fan HG, Clemons M, Xu W et al (2008) A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. Support Care Cancer 16(6):577–583. https://doi.org/10.1007/s00520-007-0341-9
Mars RB, Neubert F-X, Noonan MP, Sallet J, Toni I, Rushworth MF (2012) On the relationship between the “default mode network” and the “social brain”. Front Hum Neurosci 6:189. https://doi.org/10.3389/fnhum.2012.00189
Matsos A, Johnston IN (2019) Chemotherapy-induced cognitive impairments: a systematic review of the animal literature. Neurosci Biobehav Rev 102:382–399. https://doi.org/10.1016/j.neubiorev.2019.05.001
Mayer DK, Nasso SF, Earp JA (2017) Defining cancer survivors, their needs, and perspectives on survivorship health care in the USA. Lancet Oncol 18(1):e11–e18. https://doi.org/10.1016/S1470-2045(16)30573-3
McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ (2012) Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study. J Clin Oncol 30(20):2500–2508. https://doi.org/10.1200/jco.2011.38.5674
McDonald BC, Conroy SK, Smith DJ, West JD, Saykin AJ (2013) Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: a replication and extension study. Brain Behav Immun 30(Suppl):S117–S125. https://doi.org/10.1016/j.bbi.2012.05.007
Megari K (2020) Neuropsychological functioning among patients with different types of cancer: Postchemotherapy cognitive impairment and implications for rehabilitation. Neuropsychiatr. https://doi.org/10.1007/s40211-020-00345-x
Mehlsen M, Pedersen AD, Jensen AB, Zachariae R (2009) No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy. Psychooncology 18(3):248–257. https://doi.org/10.1002/pon.1398
Menning S, de Ruiter MB, Kieffer JM et al (2016) Cognitive impairment in a subset of breast cancer patients after systemic therapy-results from a longitudinal study. J Pain Symptom Manage 52(4):560-569.e1. https://doi.org/10.1016/j.jpainsymman.2016.04.012
Menning S, de Ruiter MB, Veltman DJ et al (2017) Changes in brain activation in breast cancer patients depend on cognitive domain and treatment type. PLoS ONE 12(3):e0171724. https://doi.org/10.1371/journal.pone.0171724
Menning S, de Ruiter MB, Veltman DJ et al (2018) Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study. Brain Imaging Behav 12(2):324–334. https://doi.org/10.1007/s11682-017-9695-x
Meyers CA, Albitar M, Estey E (2005) Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 104(4):788–793. https://doi.org/10.1002/cncr.21234
Miao H, Chen X, Yan Y et al (2016) Functional connectivity change of brain default mode network in breast cancer patients after chemotherapy. Neuroradiology 58(9):921–928. https://doi.org/10.1007/s00234-016-1708-8
Michalak S, Rybacka-Mossakowska J, Ambrosius W et al (2016) The markers of glutamate metabolism in peripheral blood mononuclear cells and neurological complications in lung cancer patients. Dis Markers 2016:2895972. https://doi.org/10.1155/2016/2895972
Miller KD, Nogueira L, Mariotto AB et al (2019) (2019) Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 69(5):363–385. https://doi.org/10.3322/caac.21565
Minagar A, Alexander JS (2003) Blood-brain barrier disruption in multiple sclerosis. Multiple Sclerosis J 9(6):540–549. https://doi.org/10.1191/1352458503ms965oa
Minisini AM, De Faccio S, Ermacora P et al (2008) Cognitive functions and elderly cancer patients receiving anticancer treatment: a prospective study. Crit Rev Oncol Hematol 67(1):71–79. https://doi.org/10.1016/j.critrevonc.2008.02.004
Mo C, Lin H, Fu F et al (2017) Chemotherapy-induced changes of cerebral activity in resting-state functional magnetic resonance imaging and cerebral white matter in diffusion tensor imaging. Oncotarget 8(46):81273–81284. https://doi.org/10.18632/oncotarget.18111
Moore HC, Parsons MW, Yue GH, Rybicki LA, Siemionow W (2014) Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction. Supp Care Cancer 22(8):2127–2131. https://doi.org/10.1007/s00520-014-2197-0
Morin RT, Midlarsky E (2018) Treatment with chemotherapy and cognitive functioning in older adult cancer survivors. Arch Phys Med Rehabil 99(2):257–263. https://doi.org/10.1016/j.apmr.2017.06.016
Morse R, Rodgers J, Verrill M, Kendell K (2003) Neuropsychological functioning following systemic treatment in women treated for breast cancer: a review. Eur J Cancer 39(16):2288–2297. https://doi.org/10.1016/s0959-8049(03)00600-2
Moruno-Manchon JF, Uzor NE, Kesler SR et al (2016) TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin. Aging (albany NY) 8(12):3507–3519. https://doi.org/10.18632/aging.101144
Mu L, Wang J, Cao B et al (2015) Impairment of cognitive function by chemotherapy: association with the disruption of phase-locking and synchronization in anterior cingulate cortex. Mol Brain 8:32. https://doi.org/10.1186/s13041-015-0125-y
Mustafa S, Walker A, Bennett G, Wigmore PM (2008) 5-Fluorouracil chemotherapy affects spatial working memory and newborn neurons in the adult rat hippocampus. Eur J Neurosci 28(2):323–330. https://doi.org/10.1111/j.1460-9568.2008.06325.x
Muzzatti B, Giovannini L, Flaiban C, Cattaruzza N, Annunziata MA (2017) Cognitive functioning in long-term cancer survivorship: a survey utilizing both standardized neuropsychological and self-report measures. Appl Neuropsychol Adult:1–8 https://doi.org/10.1080/23279095.2017.1387551
Myers JS (2010) Neuropsychologic testing for chemotherapy-related cognitive impairment. Chemo Fog. Adv Exp Med Biol 678:55–69. https://doi.org/10.1007/978-1-4419-6306-2_9
Nandakumar K, Ramalingayya G, Nayak P, et al. (2018) Naringin ameliorates doxorubicin-induced neurotoxicity In vitro and cognitive dysfunction In vivo. Pharmacognosy Magazine 14(55):https://doi.org/10.4103/pm.pm_364_17
Natori A, Ogata T, Sumitani M, Kogure T, Yamauchi T, Yamauchi H (2015) Potential role of pNF-H, a biomarker of axonal damage in the central nervous system, as a predictive marker of chemotherapy-induced cognitive impairment. Clin Cancer Res 21(6):1348–1352. https://doi.org/10.1158/1078-0432.ccr-14-2775
Nelson DL, Cox MM (2013) Bioenergetics and metabolism lehninger principles of biochemistry, 6th edn. Macmillan Higher Education, pp 764–765
Ng T, Teo SM, Yeo HL et al (2016) Brain-derived neurotrophic factor genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early-stage breast cancer. Neuro Oncol 18(2):244–251. https://doi.org/10.1093/neuonc/nov162
Nguyen CM, Yamada TH, Beglinger LJ, Cavanaugh JE, Denburg NL, Schultz SK (2013) Cognitive features 10 or more years after successful breast cancer survival: comparisons across types of cancer interventions. Psychooncology 22(4):862–868. https://doi.org/10.1002/pon.3086
Nguyen LD, Ehrlich BE (2020) Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases. EMBO Mol Med 12(6):e12075. https://doi.org/10.15252/emmm.202012075
Noh T, Walbert T (2018) Brain metastasis: clinical manifestations, symptom management, and palliative care. Handbook Clin Neurol 149:75–88. https://doi.org/10.1016/b978-0-12-811161-1.00006-2
Nudelman KN, Wang Y, McDonald BC et al (2014) Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion. PLoS ONE 9(5):e96713. https://doi.org/10.1371/journal.pone.0096713
Ohnishi T, Tamai I, Sakanaka K et al (1995) In vivo and in vitro evidence for ATP-dependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier. Biochem Pharmacol 49(10):1541–1544
Olver I, Carey M, Boyes A et al (2018) The timeliness of patients reporting the side effects of chemotherapy. Supportive Care Cancer 26(10):3579–3586. https://doi.org/10.1007/s00520-018-4225-y
Oxman TE, Schnurr PP, Silberfarb PM (1986) Assessment of cognitive function in cancer patients. Hosp J 2(3):99–128
Oxman TE, Silberfarb PM (1980) Serial cognitive testing in cancer patients receiving chemotherapy. Am J Psychiatry 137(10):1263–1265. https://doi.org/10.1176/ajp.137.10.1263
Palesh O, Scheiber C, Kesler S, Mustian K, Koopman C, Schapira L (2018) Management of side effects during and post-treatment in breast cancer survivors. Breast J 24(2):167–175. https://doi.org/10.1111/tbj.12862
Park SH, Lee WK, Chung M et al (2006) Quality of life in patients with advanced gastric cancer treated with second-line chemotherapy. Cancer Chemother Pharmacol 57(3):289–294. https://doi.org/10.1007/s00280-005-0055-y
Parsons MW, Dietrich J (2019) Assessment and management of cognitive changes in patients with cancer. Cancer. https://doi.org/10.1002/cncr.31905
Pedersen AD, Rossen P, Mehlsen MY, Pedersen CG, Zachariae R, von der Maase H (2009) Long-term cognitive function following chemotherapy in patients with testicular cancer. J Int Neuropsychol Soc 15(2):296–301. https://doi.org/10.1017/s1355617709090316
Pendergrass JC, Targum SD, Harrison JE (2018) Cognitive impairment associated with cancer: a brief review. Innov Clin Neurosci 15(1–2):36–44
Pereira J, Hanson J, Bruera E (1997) The frequency and clinical course of cognitive impairment in patients with terminal cancer. Cancer 79(4):835–842
Pergolizzi D, Root JC, Pan H et al (2019) Episodic memory for visual scenes suggests compensatory brain activity in breast cancer patients: a prospective longitudinal fMRI study. Brain Imaging Behav. https://doi.org/10.1007/s11682-019-00038-2
Piccirillo JF, Hardin FM, Nicklaus J et al (2015) Cognitive impairment after chemotherapy related to atypical network architecture for executive control. Oncology 88(6):360–368. https://doi.org/10.1159/000370117
Pomykala KL, Ganz PA, Bower JE et al (2013) The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer. Brain Imaging Behav 7(4):511–523. https://doi.org/10.1007/s11682-013-9243-2
Ponto LL, Menda Y, Magnotta VA, Yamada TH, Denburg NL, Schultz SK (2015) Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study. Int J Geriatr Psychiatry 30(6):587–594. https://doi.org/10.1002/gps.4189
Prokasheva S, Faran Y, Cwikel J, Geffen DB (2011) Analysis of memory deficits following chemotherapy in breast cancer survivors: evidence from the doors and people test. J Psychosoc Oncol 29(5):499–514. https://doi.org/10.1080/07347332.2011.600751
Purves D (2004) Neural signaling neuroscience, 3rd edn. Sinauer Associates, pp 129–142
Quesnel C, Savard J, Ivers H (2009) Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 116(1):113–123. https://doi.org/10.1007/s10549-008-0114-2
Ramalho M, Fontes F, Ruano L, Pereira S, Lunet N (2017) Cognitive impairment in the first year after breast cancer diagnosis: a prospective cohort study. Breast 32:173–178. https://doi.org/10.1016/j.breast.2017.01.018
Reid-Arndt SA, Yee A, Perry MC, Hsieh C (2009) Cognitive and psychological factors associated with early posttreatment functional outcomes in breast cancer survivors. J Psychosoc Oncol 27(4):415–434. https://doi.org/10.1080/07347330903183117
Ren X, Boriero D, Chaiswing L, Bondada S, St Clair DK (1865) Butterfield DA (2019a) Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors. Biochim Biophys Acta Mol Basis Dis 6:1088–1097. https://doi.org/10.1016/j.bbadis.2019.02.007
Ren X, Keeney JTR, Miriyala S et al (2019b) The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment (“chemobrain”) involving TNF-alpha. Free Radic Biol Med 134:1–8. https://doi.org/10.1016/j.freeradbiomed.2018.12.029
Ren X, St Clair DK, Butterfield DA (2017) Dysregulation of cytokine mediated chemotherapy induced cognitive impairment. Pharmacol Res 117:267–273. https://doi.org/10.1016/j.phrs.2017.01.001
Rice A, Michaelis ML, Georg G, Liu Y, Turunen B, Audus KL (2003) Overcoming the blood-brain barrier to taxane delivery for neurodegenerative diseases and brain tumors. J Mol Neurosci 20(3):339–343. https://doi.org/10.1385/JMN:20:3:339
Richardson J, Smith J, McCall G, Richardson A, Pilkington K, Kirsch I (2007) Hypnosis for nausea and vomiting in cancer chemotherapy: a systematic review of the research evidence. Euro J Cancer Care 16(5):402–412. https://doi.org/10.1111/j.1365-2354.2006.00736.x
Ruiz-Ojeda FJ, Olza J, Gil Á, Aguilera CM (2018) Oxidative Stress and Inflammation in Obesity and Metabolic Syndrome Obesity. p 1–15
Sadighi S, Mohagheghi MA, Montazeri A, Sadighi Z (2006) Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF). BMC Cancer 6:274. https://doi.org/10.1186/1471-2407-6-274
Sales MVC, Suemoto CK, Apolinario D et al (2019) Effects of adjuvant chemotherapy on cognitive function of patients with early-stage colorectal cancer. Clin Colorectal Cancer 18(1):19–27. https://doi.org/10.1016/j.clcc.2018.09.002
Sardi I, La Marca G, Giovannini MG et al (2011) Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry. Cancer Chemother Pharmacol 67(6):1333–1340. https://doi.org/10.1007/s00280-010-1429-3
Schagen SB, Boogerd W, Muller MJ et al (2008) Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer. Acta Oncol 47(1):63–70. https://doi.org/10.1080/02841860701518058
Schagen SB, Hamburger HL, Muller MJ, Boogerd W, van Dam FS (2001) Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function. J Neurooncol 51(2):159–165. https://doi.org/10.1023/a:1010635229762
Schagen SB, Muller MJ, Boogerd W, Mellenbergh GJ, Van Dam FS (2006) Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Cancer Inst 98(23):1742–1745. https://doi.org/10.1093/jnci/djj470
Schagen SB, Muller MJ, Boogerd W et al (2002) Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in breast cancer patients. Ann Oncol 13(9):1387–1397. https://doi.org/10.1023/a:101063522976
Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF (1999) Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 85(3):640–650
Scherling CS, Smith A (2013) Opening up the window into “chemobrain”: a neuroimaging review. Sensors (basel) 13(3):3169–3203. https://doi.org/10.3390/s130303169
Schrauwen W, Van de Cavey J, Vingerhoets G, Vanheule S, Van den Broecke R, Denys H (2020) Heterogeneous response of chemotherapy-related cognitive decline in patients with breast cancer: a prospective study. J Int Neuropsychol Soc 26(8):806–814. https://doi.org/10.1017/s1355617720000296
Seigers R, Fardell JE (2011) Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research. Neurosci Biobehav Rev 35(3):729–741. https://doi.org/10.1016/j.neubiorev.2010.09.006
Seigers R, Loos M, Van Tellingen O, Boogerd W, Smit AB, Schagen SB (2016) Neurobiological changes by cytotoxic agents in mice. Behav Brain Res 299:19–26. https://doi.org/10.1016/j.bbr.2015.10.057
Seigers R, Schagen SB, Beerling W et al (2008) Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat. Behav Brain Res 186(2):168–175. https://doi.org/10.1016/j.bbr.2007.08.004
Seigers R, Schagen SB, Coppens CM et al (2009) Methotrexate decreases hippocampal cell proliferation and induces memory deficits in rats. Behav Brain Res 201(2):279–284. https://doi.org/10.1016/j.bbr.2009.02.025
Seigers R, Schagen SB, Van Tellingen O, Dietrich J (2013) Chemotherapy-related cognitive dysfunction: current animal studies and future directions. Brain Imaging Behav 7(4):453–459. https://doi.org/10.1007/s11682-013-9250-3
Seiter K (2005) Toxicity of the topoisomerase II inhibitors. Expert Opin Drug Safety 4(2):219–234. https://doi.org/10.1517/14740338.4.2.219
Seo EJ, Klauck SM, Efferth T, Panossian A (2018) Adaptogens in chemobrain (Part I): Plant extracts attenuate cancer chemotherapy-induced cognitive impairment—Transcriptome-wide microarray profiles of neuroglia cells. Phytomedicine 55:80–91. https://doi.org/10.1016/j.phymed.2018.10.022
Shen CY, Chen VC, Yeh DC et al (2019) Association of functional dorsal attention network alterations with breast cancer and chemotherapy. Sci Rep 9(1):104. https://doi.org/10.1038/s41598-018-36380-6
Shih YC, Smieliauskas F, Geynisman DM, Kelly RJ, Smith TJ (2015) Trends in the cost and use of targeted cancer therapies for the privately insured nonelderly: 2001 to 2011. J Clin Oncol 33(19):2190–2196. https://doi.org/10.1200/jco.2014.58.2320
Shilling V, Jenkins V (2007) Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer. Eur J Oncol Nurs 11(1):6–15. https://doi.org/10.1016/j.ejon.2006.02.005
Shilling V, Jenkins V, Morris R, Deutsch G, Bloomfield D (2005) The effects of adjuvant chemotherapy on cognition in women with breast cancer–preliminary results of an observational longitudinal study. Breast 14(2):142–150. https://doi.org/10.1016/j.breast.2004.10.004
Siddiqui T, Deshmukh VD, Karimjee N (1992) Subclinical cognitive deficits in cancer patients: a preliminary P300 study. Clin Electroencephalogr 23(3):132–136
Silverman DH, Dy CJ, Castellon SA et al (2007) Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat 103(3):303–311. https://doi.org/10.1007/s10549-006-9380-z
Simo M, Gurtubay-Antolin A, Vaquero L, Bruna J, Rodriguez-Fornells A (2018) Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures. Neuroimage Clin 18:86–96. https://doi.org/10.1016/j.nicl.2017.12.032
Simo M, Rifa-Ros X, Rodriguez-Fornells A, Bruna J (2013) Chemobrain: a systematic review of structural and functional neuroimaging studies. Neurosci Biobehav Rev 37(8):1311–1321. https://doi.org/10.1016/j.neubiorev.2013.04.015
Skaali T, Fossa SD, Andersson S et al (2011) A prospective study of neuropsychological functioning in testicular cancer patients. Ann Oncol 22(5):1062–1070. https://doi.org/10.1093/annonc/mdq553
Small BJ, Rawson KS, Walsh E et al (2011) Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors. Cancer 117(7):1369–1376. https://doi.org/10.1002/cncr.25685
Smith JA, Das A, Ray SK, Banik NL (2012) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 87(1):10–20. https://doi.org/10.1016/j.brainresbull.2011.10.004
Snell RS (2010) Clinical neuroanatomy. Lippincott Williams & Wilkins
Sorokin J, Saboury B, Ahn JA, Moghbel M, Basu S, Alavi A (2014) Adverse functional effects of chemotherapy on whole-brain metabolism: a PET/CT quantitative analysis of FDG metabolic pattern of the “chemo-brain.” Clin Nucl Med 39(1):e35–e39. https://doi.org/10.1097/RLU.0b013e318292aa81
Stewart A, Collins B, Mackenzie J, Tomiak E, Verma S, Bielajew C (2008) The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology 17(2):122–130. https://doi.org/10.1002/pon.1210
Stewart DJ, Grewaal D, Green RM et al (1993) Concentrations of doxorubicin and its metabolites in human autopsy heart and other tissues. Anticancer Res 13(6a):1945–1952
Stouten-Kemperman MM, de Ruiter MB, Caan MW et al (2015) Lower cognitive performance and white matter changes in testicular cancer survivors 10 years after chemotherapy. Hum Brain Mapp 36(11):4638–4647. https://doi.org/10.1002/hbm.22942
Tacar O, Sriamornsak P, Dass CR (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65(2):157–170. https://doi.org/10.1111/j.2042-7158.2012.01567.x
Tager FA, McKinley PS, Schnabel FR et al (2010) The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study. Breast Cancer Res Treat 123(1):25–34. https://doi.org/10.1007/s10549-009-0606-8
Tangpong J, Cole MP, Sultana R et al (2006) Adriamycin-induced, TNF-α-mediated central nervous system toxicity. Neurobiol Dis 23(1):127–139. https://doi.org/10.1016/j.nbd.2006.02.013
Tangpong J, Miriyala S, Noel T, Sinthupibulyakit C, Jungsuwadee P, St Clair DK (2011) Doxorubicin-induced central nervous system toxicity and protection by xanthone derivative of Garcinia mangostana. Neuroscience 175:292–299. https://doi.org/10.1016/j.neuroscience.2010.11.007
Tao L, Lin H, Yan Y, et al. (2017) Impairment of the executive function in breast cancer patients receiving chemotherapy treatment: a functional MRI study. Eur J Cancer Care (Engl) 26(6) doi:https://doi.org/10.1111/ecc.12553
Tao L, Wang L, Chen X et al (2020) Modulation of Interhemispheric functional coordination in breast cancer patients receiving chemotherapy. Front Psychol 11:1689. https://doi.org/10.3389/fpsyg.2020.01689
Tchen N, Juffs HG, Downie FP et al (2003) Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol 21(22):4175–4183. https://doi.org/10.1200/jco.2003.01.119
Thomas TC, Beitchman JA, Pomerleau F et al (2017) Acute treatment with doxorubicin affects glutamate neurotransmission in the mouse frontal cortex and hippocampus. Brain Res 1672:10–17. https://doi.org/10.1016/j.brainres.2017.07.003
Tong Y, Wang K, Sheng S, Cui J (2020) Polydatin ameliorates chemotherapy-induced cognitive impairment (chemobrain) by inhibiting oxidative stress, inflammatory response, and apoptosis in rats. Biosci Biotechnol Biochem 84(6):1201–1210. https://doi.org/10.1080/09168451.2020.1722057
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P (2008) Redox regulation of cell survival. Antioxid Redox Signal 10(8):1343–1374. https://doi.org/10.1089/ars.2007.1957
Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, Capella G (2010) Recent advances in cancer therapy: an overview. Curr Pharmaceutical Des 16(1):3–10. https://doi.org/10.2174/138161210789941847
Utne I, Loyland B, Grov EK et al (2018) Distinct attentional function profiles in older adults receiving cancer chemotherapy. Eur J Oncol Nurs 36:32–39. https://doi.org/10.1016/j.ejon.2018.08.006
van Dam FS, Schagen SB, Muller MJ et al (1998) Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst 90(3):210–218
Van Dyk K, Bower JE, Crespi CM, Petersen L, Ganz PA (2018) Cognitive function following breast cancer treatment and associations with concurrent symptoms. NPJ Breast Cancer 4:25. https://doi.org/10.1038/s41523-018-0076-4
Vearncombe KJ, Rolfe M, Wright M, Pachana NA, Andrew B, Beadle G (2009) Predictors of cognitive decline after chemotherapy in breast cancer patients. J Int Neuropsychol Soc 15(6):951–962. https://doi.org/10.1017/s1355617709990567
Vitor T, Kozasa EH, Bressan RA et al (2019) Impaired brain dopamine transporter in chemobrain patients submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1. Ann Nucl Med 33(4):269–279. https://doi.org/10.1007/s12149-019-01331-2
Von Ah D, Harvison KW, Monahan PO et al (2009) Cognitive function in breast cancer survivors compared to healthy age- and education-matched women. Clin Neuropsychol 23(4):661–674. https://doi.org/10.1080/13854040802541439
Wahdan SA, El-Derany MO, Abdel-Maged AE, Azab SS (2020) Abrogating doxorubicin-induced chemobrain by immunomodulators IFN-beta 1a or infliximab: Insights to neuroimmune mechanistic hallmarks. Neurochem Int 138:104777. https://doi.org/10.1016/j.neuint.2020.104777
Wang C, Zhao Y, Wang L et al (2021) C-phycocyanin mitigates cognitive impairment in doxorubicin-induced chemobrain: impact on neuroinflammation, oxidative stress, and brain mitochondrial and synaptic alterations. Neurochem Res 46(2):149–158. https://doi.org/10.1007/s11064-020-03164-2
Wang D, Wang B, Liu Y, Dong X, Su Y, Li S (2019) Protective effects of ACY-1215 against chemotherapy-related cognitive impairment and brain damage in mice. Neurochem Res 44(11):2460–2469. https://doi.org/10.1007/s11064-019-02882-6
Wang L, Apple AC, Schroeder MP et al (2016) Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls. Cancer 122(2):258–268. https://doi.org/10.1002/cncr.29737
Wang L, Zou L, Chen Q et al (2020) Gray matter structural network disruptions in survivors of acute lymphoblastic leukemia with chemotherapy treatment. Acad Radiol 27(3):e27–e34. https://doi.org/10.1016/j.acra.2019.04.010
Wang XM, Walitt B, Saligan L, Tiwari AF, Cheung CW, Zhang ZJ (2015) Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy. Cytokine 72(1):86–96. https://doi.org/10.1016/j.cyto.2014.12.006
Wefel JS, Lenzi R, Theriault R, Buzdar AU, Cruickshank S, Meyers CA (2004a) “Chemobrain” in breast carcinoma? a prologue. Cancer 101(3):466–475. https://doi.org/10.1002/cncr.20393
Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA (2004b) The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer 100(11):2292–2299. https://doi.org/10.1002/cncr.20272
Wefel JS, Saleeba AK, Buzdar AU, Meyers CA (2010) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 116(14):3348–3356. https://doi.org/10.1002/cncr.25098
Weiss B (2008) Chemobrain: a translational challenge for neurotoxicology. Neurotoxicology 29(5):891–898. https://doi.org/10.1016/j.neuro.2008.03.009
Weiss HD, Walker MD, Wiernik PH (1974a) Neurotoxicity of commonly used antineoplastic agents. N Engl J Med 291(3):127–133
Weiss HD, Walker MD, Wiernik PH (1974b) Neurotoxicity of commonly used antineoplastic agents (second of two parts). New Engl J Med 291(3):127–133. https://doi.org/10.1056/nejm197407182910305
Whitford HS, Kalinowski P, Schembri A et al (2019) The impact of chemotherapy on cognitive function: a multicentre prospective cohort study in testicular cancer. Support Care Cancer. https://doi.org/10.1007/s00520-019-05095-3
Whitford HS, Kalinowski P, Schembri A et al (2020) The impact of chemotherapy on cognitive function: a multicentre prospective cohort study in testicular cancer. Support Care Cancer 28(7):3081–3091. https://doi.org/10.1007/s00520-019-05095-3
Wieneke MH, Dienst ER (1995) Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psycho-Oncol 4(1):61–66
Wigmore PM, Mustafa S, El-Beltagy M, Lyons L, Umka J, Bennett G (2010) Effects of 5-FU. Adv Exp Med Biol 678:157–164. https://doi.org/10.1007/978-1-4419-6306-2_20
Williams AM, Shah R, Shayne M et al (2018) Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. J Neuroimmunol 314:17–23. https://doi.org/10.1016/j.jneuroim.2017.10.005
Williams AM, van Wijngaarden E, Seplaki CL et al (2020) Cognitive function in patients with chronic lymphocytic leukemia: a cross-sectional study examining effects of disease and treatment. Leuk Lymphoma 61(7):1627–1635. https://doi.org/10.1080/10428194.2020.1728748
Wouters H, Baars JW, Schagen SB (2016) Neurocognitive function of lymphoma patients after treatment with chemotherapy. Acta Oncol 55(9–10):1121–1125. https://doi.org/10.1080/0284186x.2016.1189092
Xu Z, Luo F, Wang Y et al (2020) Cognitive impairments in breast cancer survivors treated with chemotherapy: a study based on event-related potentials. Cancer Chemother Pharmacol 85(1):61–67. https://doi.org/10.1007/s00280-019-03994-0
Yamada TH, Denburg NL, Beglinger LJ, Schultz SK (2010) Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. J Neuropsychiatry Clin Neurosci 22(1):48–54. https://doi.org/10.1176/appi.neuropsych.22.1.48
Yang GS, Mi X, Jackson-Cook CK et al (2020) Differential DNA methylation following chemotherapy for breast cancer is associated with lack of memory improvement at one year. Epigenetics 15(5):499–510. https://doi.org/10.1080/15592294.2019.1699695
Yang H, Villani RM, Wang H et al (2018) The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res 37(1):266–266. https://doi.org/10.1186/s13046-018-0909-x
Yang M, Kim JS, Kim J et al (2012) Acute treatment with methotrexate induces hippocampal dysfunction in a mouse model of breast cancer. Brain Res Bull 89(1–2):50–56. https://doi.org/10.1016/j.brainresbull.2012.07.003
Yarlagadda A, Alfson E, Clayton AH (2009) The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (edgmont) 6(11):18–22
Yokoyama C, Sueyoshi Y, Ema M, Mori Y, Takaishi K, Hisatomi H (2017) Induction of oxidative stress by anticancer drugs in the presence and absence of cells. Oncol Lett 14(5):6066–6070. https://doi.org/10.3892/ol.2017.6931
Zeng Y, Cheng ASK, Song T et al (2019) Changes in functional brain networks and neurocognitive function in Chinese gynecological cancer patients after chemotherapy: a prospective longitudinal study. BMC Cancer 19(1):386. https://doi.org/10.1186/s12885-019-5576-6
Zhang J-M, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2):27–37. https://doi.org/10.1097/AIA.0b013e318034194e
Zhang J, Zhang L, Yan Y et al (2015) Are capecitabine and the active metabolite 5-FU CNS penetrable to treat breast cancer brain metastasis? Drug Metab Disposition 43(3):411–417. https://doi.org/10.1124/dmd.114.061820
Zhang Y, Chen YC, Hu L et al (2019) Chemotherapy-induced functional changes of the default mode network in patients with lung cancer. Brain Imaging Behav. https://doi.org/10.1007/s11682-018-0030-y
Zheng Y, Luo J, Bao P et al (2014) Long-term cognitive function change among breast cancer survivors. Breast Cancer Res Treat 146(3):599–609. https://doi.org/10.1007/s10549-014-3044-1
Zhou W, Kavelaars A, Heijnen CJ (2016) Metformin prevents cisplatin-induced cognitive impairment and brain damage in mice. PLoS ONE 11(3):e0151890. https://doi.org/10.1371/journal.pone.0151890
Zhou X, Xu P, Dang R et al (2018) The involvement of autophagic flux in the development and recovery of doxorubicin-induced neurotoxicity. Free Radical Biol Med 129:440–445. https://doi.org/10.1016/j.freeradbiomed.2018.10.418
Zimberg M, Berenson S (1990) Delirium in patients with cancer: nursing assessment and intervention. Oncol Nurs Forum 17(4):529–538
Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5(6):311. https://doi.org/10.1038/nrneurol.2009.54
Zuniga KE, Bishop NJ (2018) Recent cancer treatment and memory decline in older adults: An analysis of the 2002–2012 Health and Retirement Study. J Geriatr Oncol 9(3):186–193. https://doi.org/10.1016/j.jgo.2017.10.004
Acknowledgements
This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and through the project EXPL/MED-FAR/0203/2021. The work also received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821528 (NeuroDeRisk: Neurotoxicity De-Risking in Preclinical Drug Discovery). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). A. Dias-Carvalho acknowledges FCT and UCIBIO for her PhD grant (UI/BD/151318/2021). VMC acknowledges FCT for her grant (SFRH/BD/129359/2017), being the later funded by national funds through FCT under the Norma Transitória – DL57/2016/CP1334/CT0006.
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Dias-Carvalho, A., Ferreira, M., Ferreira, R. et al. Four decades of chemotherapy-induced cognitive dysfunction: comprehensive review of clinical, animal and in vitro studies, and insights of key initiating events. Arch Toxicol 96, 11–78 (2022). https://doi.org/10.1007/s00204-021-03171-4
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DOI: https://doi.org/10.1007/s00204-021-03171-4