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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Semin Oncol. Author manuscript; available in PMC 2012 June 1.
Published in final edited form as:
PMCID: PMC3120018


Michelle C. Janelsins, Ph.D.,1 Sadhna Kohli, Ph.D., M.P.H.,2 Supriya G. Mohile, M.D., M.S.,3 Kenneth Usuki, M.D.,1 Tim A. Ahles, Ph.D.,4 and Gary R. Morrow, Ph.D., M.S.1,5


The purpose of this review is to summarize the current literature on the effects of cancer treatment-related cognitive difficulties, with a focus on the effects of chemotherapy. Numerous patients have cognitive difficulties during and after cancer treatments and, for some, these last years after treatment. We do not yet fully understand which factors increase susceptibility to cognitive difficulties during treatment and which cause persistent problems. We review possible contributors, including genetic and biological factors. Mostly we focus is on cognitive effects of adjuvant chemotherapy for breast cancer; however, cognitive effects of chemotherapy on the elderly and brain tumor patients are also discussed.


Up to 75% of cancer patients experience cognitive impairment (e.g., problems with memory, executive functioning, and attention) during or after treatment of their cancer. For many (up to 35%), this persists for months or years following treatment.[1-6] With over 11 million cancer survivors in the United States,[7] up to 3.9 million individuals may be living with long-lasting cognitive difficulties from cancer and cancer treatments. This is an important area, because these could influence adherence to treatments and lead to long-term impairment. Cognitive deficits that occur from cancer or its treatment vary and may be subtle or dramatic, temporary or permanent, and stable or progressive [8]. We highlight recent work in cancer- and chemotherapy-related cognitive difficulties and explore possible mechanisms.


Some cognitive problems in those who receive chemotherapy are more severe than in those who only receive locoregional therapy (e.g. radiation, surgery).[9, 10] Cognitive problems with chemotherapy can negatively impact activities of daily living such as 1) work performance,[5] 2) access to medical and other health services, 3) caring for and socially interacting with family members.[11]

Systematic research to understand cognitive difficulties with chemotherapy was first reported during the mid 1990s to early 2000’s;[2-4, 12] early studies often did not include pre-treatment assessment data and/or were cross-sectional in design. The lack of pre-treatment data was most likely due to difficulty obtaining such information from newly diagnosed patients. Studies over the past decade have incorporated pre-treatment assessments of cognitive function. The importance of a pre-treatment baseline was evidenced in a study[5] of the effects of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy on cognitive function in breast cancer. This was one of the first prospective, longitudinal studies to assess cognitive function with pre-treatment and post-treatment cognitive measures. There were no overall mean differences in cognitive function between patients and controls (normative data). Within-subject analyses showed that 61% had cognitive declines in learning, attention, and processing speed. If the pre-treatment assessment had been unavailable, 46% would not have had detectable cognitive impairments (because their post-treatment assessment scores were normal). This is extremely important since cognitive dysfunction can be subtle. If a patient scores well on a cognitive test before chemotherapy and less well after treatment (but that score is still within the normal range), the decline may nevertheless represent a clinically significant difference.

Approximately ten additional longitudinal studies have investigated cancer- and/or treatment-related cognitive difficulties; many treatment studies assessed the effects of chemotherapy and used standard neuropsychological assessments.[10, 13-23] In all, 12-82% of patients had cognitive difficulties in the domains of executive function, memory, psychomotor speed, and attention. Not all studies revealed significant changes in all domains; those in memory, executive function, processing speed, and attention appear most frequent. Additionally, many studies had small numbers and were not powered to test multiple cognitive domains. These studies utilized a variety of cognitive assessments and control groups, and most investigated patients on various treatment regimens. One recent study compared patients exposed to chemotherapy, those not exposed, and a healthy control group; those exposed to chemotherapy had the greatest deficits.[21]

Several studies have shown cognitive deficits in cancer patients before chemotherapy.[5, 22] For example, in one study 33% of patients had cognitive difficulties in verbal learning and memory prior to chemotherapy[5]. Another recent study revealed that 23% of women being treated for breast cancer had difficulty before chemotherapy.[22] These could be related to psychological variables related to cancer diagnosis (e.g., stress, anxiety, depression) or to other factors (e.g., cognitive reserve). More research is needed to explicitly understand factors that lead to cognitive difficulties before and during treatment, and to understand those that contribute to long-lasting impairment.

Most studies of chemotherapy-related cognitive difficulties have focused on breast cancer. Longitudinal studies are needed in other disease groups to understand whether cognitive difficulties are more or less severe in these conditions. For example, in a cross-sectional study,[3] breast and lymphoma patients showed long-term problems; however, no large prospective study in lymphoma has been conducted to confirm this. More work is needed in well-powered long-term observational studies to understand the course and severity of cognitive difficulties, and possible mechanisms of action.


We are far from understanding the underlying molecular mechanisms that contribute to cognitive difficulties. Various biological and psychological mechanisms have been proposed (Figure 1). Assessment of various biological factors (e.g., inflammatory markers, genetic markers, and brain imaging) may help identify high risk groups for cognitive difficulties or those at highest risk for persistent long-term effects. Although we currently have no treatments for cognitive difficulties in cancer patients, identifying biological markers related to cognitive function would enable us to understand possible mechanisms and eventually develop successful interventions.


Brain Volume, Activity, and Metabolism

Subtle cognitive changes pose unique challenges to detection and management. First, the cause may not be apparent, and the impairments not evaluable with standard, objective neuropsychological measures. Second, subtle cognitive changes may be confounded by other problems commonly associated with cancer and its treatment, like depression, anxiety, and fatigue.

To develop prophylactic interventions, we must understand the mechanisms behind the effects of treatment on cognition. We need to use every tool at our disposal, not only to document the extent of the cognitive changes via neuropsychological testing, but also to probe changes in brain volume, metabolic status, and central nervous system (CNS) activity following treatment. Documenting these changes is possible with neuroimaging techniques. These include Computerized Tomography (CT), Single Photon Emission-Computed Tomography (SPECT), Positron Emission Tomography (PET), and Magnetic Resonance (MR). The latter two are particularly powerful because they allow one to assess metabolic activity (PET via radiolabeling and MR via various spectroscopic techniques). MR has particular value because of the range of techniques available to probe brain anatomy and physiology. These include high resolution anatomical images, which allow accurate measurement of therapy-induced changes in gray and white matter volumes. Functional MRI measures areas of brain activation during stimuli such as a motor task or neuropsychological assessment. Diffusion MRI allows measurements of the diffusivity of water in the brain. Spectroscopic MR provides information about the biochemical processes in the brain. Finally, because it does not use ionizing radiation, MR can be repeated on the same individual to assess short- or long-term longitudinal changes. Although similar studies can be done with PET, they are limited by dose exposure guidelines and may not be possible at frequent intervals.

The application of any of the neuroimaging techniques, but particularly the combination of MR techniques, will prove useful in elucidating the structural, metabolic and functional consequences of cancer and cancer therapies. Neuroimaging techniques have matured and are readily available in most clinical settings. Thus, future studies of the effects of cancer therapies on cognition should include neuroimaging, and conventional neuropsychological testing, to test hypotheses about the fundamental processes involved in the cognitive dysfunction following therapy. Preliminary work [24] showed reductions in gray matter volume of frontal and temporal brain regions over the course of chemotherapy with partial recovery after treatment; these reductions were not seen in patients not exposed to chemotherapy or in healthy controls. These data temporally coincide with functional changes in neurocognitive assessment.

Neuroimaging studies would also determine whether patients utilize compensatory mechanisms to enhance performance on neuropsychological testing even though they are aware that their function is worse than before treatment. Evidence for this hypothesis may be the lack of correlation between self-report and performance on neuropsychological testing.[25] Preliminary imaging work has demonstrated by functional MRI that a patient diagnosed with breast cancer receiving chemotherapy had to “work harder” to complete a cognitive task than her twin sister who did not have cancer.[26]

Cytokines and other Inflammation Markers

Although increased inflammatory markers are associated with cognitive difficulties in numerous neurodegenerative diseases and cognitive disorders, [27-31] there is little information about the relationship of inflammatory responses to cognitive function in cancer. Elevated peripheral levels of pro-inflammatory cytokines may be related to cognitive problems .[32] Chemotherapy has been associated with increased levels of pro-inflammatory cytokines (e.g. IL-1β) in those treated for Hodgkin’s disease.[33] In breast cancer patients receiving paclitaxel, levels of IL-6 increased 3 days after treatment compared to pre-treatment, but not in those who received a combination of fluorouracil, cyclophosphamide and methotrexate. [34] Significant changes in markers of endothelial and platelet activation were found in breast cancer on anthracycline-based treatment, further supporting the hypothesis that inflammation occurs as a result of chemotherapy .[35]

Increased levels of IL-6 have been associated with poorer executive function, whereas higher levels of IL-8 were associated with better memory performance in patients with acute myelogenous leukemia and myelodysplastic syndrome prior to treatment.[36] Another study found a trend between cytokine levels and cognitive performance in breast cancer .[37] The investigators are currently assessing cytokine levels in relationship to cognitive function (via neuropsychological and computerized tests) in an ongoing observational study of cognitive function in colorectal cancer.[38] Further clarification of the role of cytokines, chemokines and other immune factors on cognitive function in cancer is needed. Large-scale observational studies that correlate changes in cytokines and chemokines with those in cognitive function should help clarify the association between inflammation and cognitive function in cancer patients on different chemotherapy regimens.

Genetic Contributors

Only a subgroup of breast cancer survivors may experience long-term changes in cognitive ability. Several genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in genes in multiple signaling pathways (i.e. inflammation, dopamine, DNA repair, oxidative stress) perhaps related to cognitive decline in normal aging, Alzheimer’s disease and other syndromes with cognitive decline. [39-41]

Therefore, genetic variation related to cognitive function may be associated with increased risk for long-term cognitive changes.[32] Two studies examined the association between apolipoprotein E (APOE) and catechol-o-methyltransferase (COMT) genotypes and cognitive function in cancer survivors.[42, 43]

Apolipoprotein E (ApoE) is a complex glycolipoprotein that facilitates uptake, transport, and distribution of lipids. It appears to play an important role in neuronal repair and plasticity after injury.[44] The human E4 allele has been associated with a variety of disorders with prominent cognitive dysfunction. These include otherwise normal patients with memory complaints, Alzheimer’s disease, and poor outcomes in stroke and traumatic brain injury.[45] Cancer survivors with at least one E4 allele scored significantly lower in the visual memory and spatial ability domains, with a trend to score lower in executive function compared to survivors who did not carry an E4 allele.[42]

The COMT Val158Met single nucleotide polymorphism has been associated with dopamine levels in the prefrontal cortex. COMT-Val carriers metabolize dopamine more rapidly, with less availability of a neurotransmitter critical for cognitive function. COMT-Val carriers perform more poorly on tests of attention and executive function compared to COMT-Met carriers.[45] Breast cancer survivors who were COMT-Val carriers and exposed to chemotherapy performed more poorly on tests of attention than healthy controls who were also carriers.[43]

These studies support the hypothesis that genetic factors increase vulnerability to cognitive changes with cancer treatments. Examination of other neural repair/plasticity genes and neurotransmitter activity genes, and those associated chemotherapy-induced cognitive change such as DNA damage / repair (e.g., recombination 11 homolog A[46]) or blood brain barrier damage may reveal important associations with post-treatment cognitive function.[32] Finally, increasing interest in epigenetics (changes in gene activity without any in DNA structure) and cognitive function may lead to examination of chemotherapy-induced epigenetic changes associated with cancer-treatment related cognitive impairment.[47]

Menopausal Status and Hormonal Therapies

Most evidence for cognitive difficulties in cancer patients and survivors is attributed to chemotherapy. The literature on hormonal balance and cognition suggests that menopausal status and endocrine therapy can also influence cognitive function in cancer. For example, the transition from pre- to post-menopausal status is associated with alterations in cytokines such as IL-6[48] and cognitive difficulties in learning and memory.[49] Case studies in cancer reveal that cognitive difficulties can vary among patients who received the same course of chemotherapy; this could be related to menopausal status.[50]

Breast cancer patients who received chemotherapy and tamoxifen have greater difficulty than those who received chemotherapy alone. [25] Another cross-sectional study assessing tamoxifen in pre-menopausal breast cancer patients compared to healthy controls found greater difficulty in visual and verbal memory and processing speed.[51] One prospective study found deterioration in verbal memory and executive function in post-menopausal patients taking tamoxifen for one year (but not in those taking the aromatase inhibitor, exemestane, compared to healthy controls).[52] Larger studies are needed to confirm these results and to address the combined effects of chemotherapy and endocrine therapy on cognitive function in cancer.


Impaired cognitive function is a common complaint among older patients presenting for medical treatment. The differential diagnosis of the type and extent of impairment is important in treatment planning and prognosis.[53] Cognitive disorders such as dementia limit life expectancy and can affect whether patients should receive adjuvant therapy. Cognitive disorders interfere with medication compliance and consent to treatment and increase caregiver burden. Cognitively impaired persons receive less definitive cancer care than others.[54-56]

Cognitive disorders in older patients present prior to cancer treatment are often underdiagnosed without screening. 6%-10% of people age ≥ 65 years suffer from dementia. Prevalence approaches 50% in community-living populations >80 years.[57] Cognitive impairment is associated with an increased risk for progression to dementia, with progression rates of 10%-15% per year compared with 1% to 2.5% in the cognitively intact.[58-60] One-fifth of geriatric cancer patients screen positively for cognitive disorders in an academic setting.[61, 62]


Investigators have prospectively studied the impact of cancer treatment on cognitive function in older patients with breast cancer, following complaints of memory changes and impaired concentration. The data are still limited regarding the impact of cancer treatment on an older person’s cognition. In one longitudinal prospective study of older patients with breast cancer, 51% of 45 evaluable patients perceived a decline in cognitive function after 6 months chemotherapy.[63] Other studies demonstrated no significant change in Mini-Mental Status Exam (MMSE) scores after chemotherapy or hormonal therapy over a short time period.[64, 65] In one longitudinal study, 28 older women with breast cancer scheduled for adjuvant chemotherapy underwent neuropsychological testing and a comprehensive geriatric assessment (CGA) before therapy and 6 months after completion.[14] Thirty-nine percent scored 2 standard deviations below normative data at 6 months compared to their baseline neuropsychological test scores.[14] Exploratory analyses of longitudinal CGA results demonstrated no changes in functional status, comorbidity, or depression scores.[66] At the same time, one population-based study suggests that women with breast cancer who receive chemotherapy have a higher likelihood of dementia after long-term follow-up.[67] More large, prospective, long-term studies are necessary to definitively assess the impact of breast cancer treatment on the cognitive function of older patients.

Hormonal Therapy

The cognitive effects of hormonal therapy with androgen deprivation therapy (ADT) in men with prostate cancer have conflicting results due to small sample size, short observation time, or perhaps a heterogeneous effect of ADT.[68] Several studies have evaluated ADT on the cognition of men with prostate cancer but few have described the baseline prevalence of cognitive impairment. One study examined the cognitive function of 25 men, ages 49 to 75, following 12 months of androgen deprivation.[69] They found improvements in visual and semantic memory. While not significantly different, the range on the Mini-Mental State Exam (MMSE) of the treatment group at baseline was 21-29. This suggested that some had significant cognitive impairment prior to treatment. A study of outcomes at 1 year found cognitive losses in those undergoing hormonal treatment compared to controls.[70] They also noted that the community control group performed significantly better than the prostate cancer group at baseline. This suggests that some may have cognitive impairment prior to treatment which may impact overall results. In another study of 32 patients (median age 71 years), 45% scored >1.5 standard deviations below the mean on ≥2 neuropsychological measures at baseline.[71] Within exploratory analyses, those who scored below expectation at baseline displayed no change in cognition, while people with average or better scores at baseline displayed improvements in visuospatial planning and timed tests of phonemic fluency. This again suggests that a subset have cognitive impairment before treatment which may impact overall results.

Clinical suspicion of dementia is not as sensitive as available screening tools.[72] A cognitive assessment tool (e.g., Blessed Dementia Rating Scale,[73] Mini-Mental State Examination, [74] Mini-Cog,[75] and Short Portable Mental Status Questionnaire) for older cancer patients should screen for baseline impairment and follow effects of therapy on cognitive function. The purpose of screening is to assess cognitive capacity and stratify risk; abnormal scores should trigger a comprehensive work-up with cognitive specialists. Unfortunately, these tools have not yet demonstrated the ability to detect treatment-induced changes in cognition. A more detailed neuropsychological evaluation is needed to accomplish this goal.[63]


In addition to the neurological complications brain tumors themselves impose, the treatments are often associated with harmful effects on the central nervous system that can lead to cognitive impairments. These patients may experience a broad array of both acute and late toxicities, resulting both from direct toxic effects on the nervous system and indirect dysfunction (e.g., metabolic dysregulation, cerebrovascular disorders). Toxicity from brain tumor therapy may range from focal neurological deficits to generalized neurological syndromes. These frequently include fatigue and cognitive impairment including decreased executive function.[76] Since patients with brain tumors live longer, it is important to further understand the effects chemotherapy and other treatments have on intact brain structures and cognitive function.


Animal models are especially important to the cancer and cognition field. It is not easy to assess molecular changes in the human brain. While parallel findings between animal and human experiments do not establish equivalence, animal models may inform hypotheses relating to the clinical condition. Experiments in animal models can usually be done much more quickly than parallel clinical studies and allow for many more aspects of a research question to be addressed. Furthermore, addressing a research question in an animal model is usually much less expensive than the same research question in a human study, assuming that study in a human is even technologically possible.

Animal studies have found that chemotherapy agents can negatively affect memory behavior in mice, [77-80] likely due to reductions in adult neurogenesis. [80-83] Mice exposed to adriamycin had increased cortical and hippocampal levels of TNF-α, hyperactivation of microglia, induction of oxidative stress and mitochondrial dysfunction, and increased neural cell death. This was despite the fact that adriamycin was not detected in the brains of these mice.[84, 85] These studies suggest that chemotherapy causes neurotoxicity within the brain and that inflammation may be a mediator of cognitive difficulties by reducing neural transmission. Future work in animal models will provide more mechanistic insight and allow testing of interventions for cognitive impairment.


Cancer- and chemotherapy-related cognitive impairment is an important clinical problem that negatively impacts quality of life for many individuals during treatment and post-treatment. We have reviewed various topics relevant to the cognition and cancer field and highlighted important areas for future research. Understanding the factors that lead to cognitive impairments from chemotherapy and other cancer treatments will allow us to better understand how to educate patients about these difficulties and ultimately how to treat them.


Partially supported by: NCI R25CA10618


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1. Janelsins M, Roscoe JA, Jean-Pierre P, Morrow GR. Cognitive Functioning in Breast Cancer Patients During and Following Chemotherapy. Supplement to American Society of Clinical Oncology. 2009;47 Abstract.
2. Brezden CB, et al. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol. 2000;18(14):2695–701. [PubMed]
3. Ahles TA, et al. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol. 2002;20(2):485–93. [PubMed]
4. van Dam FS, et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst. 1998;90(3):210–8. [PubMed]
5. Wefel JS, et al. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer. 2004;100(11):2292–9. [PubMed]
6. Yamada TH, et al. Neuropsychological outcomes of older breast cancer survivors: cognitive features ten or more years after chemotherapy. J Neuropsychiatry Clin Neurosci. 22(1):48–54. [PMC free article] [PubMed]
7. Cancer Facts and Figures. American Cancer Society; Atlanta, GA: 2009.
8. Schagen SB, et al. Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function. J Neurooncol. 2001;51(2):159–65. [PubMed]
9. Kohli S, Griggs JJ, Roscoe JA, Jean-Pierre P, Bole C, Mustian KM, Hill R, Smith K, Gross H, Morrow GR. Self-Reported Cognitive Impairments in Patients With Cancer. J Oncol Practice. 2007;3(2):54–59. [PMC free article] [PubMed]
10. Quesnel C, Savard J, Ivers H. Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat. 2009;116(1):113–23. [PubMed]
11. Reid-Arndt SA, et al. Cognitive and psychological factors associated with early posttreatment functional outcomes in breast cancer survivors. J Psychosoc Oncol. 2009;27(4):415–34. [PMC free article] [PubMed]
12. Wieneke M.H.a.D. Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psychooncology. 1995;4:61–6. E.R.
13. Schagen SB, et al. Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Cancer Inst. 2006;98(23):1742–5. [PubMed]
14. Hurria A, et al. Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc. 2006;54(6):925–31. [PubMed]
15. Collins B, et al. Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psychooncology. 2009;18(2):134–43. [PubMed]
16. Hermelink K, et al. Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer. 2007;109(9):1905–13. [PubMed]
17. Jenkins V, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer. 2006;94(6):828–34. [PMC free article] [PubMed]
18. Ahles TA, et al. Cognitive function in breast cancer patients prior to adjuvant treatment. Breast Cancer Res Treat. 2008;110(1):143–52. [PMC free article] [PubMed]
19. Stewart A, et al. The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology. 2008;17(2):122–30. [PubMed]
20. Ouimet LA, et al. Measuring neuropsychological change following breast cancer treatment: an analysis of statistical models. J Clin Exp Neuropsychol. 2009;31(1):73–89. [PubMed]
21. Ahles TA, et al. Longitudinal Assessment of Cognitive Changes Associated With Adjuvant Treatment for Breast Cancer: Impact of Age and Cognitive Reserve. J Clin Oncol [PMC free article] [PubMed]
22. Jansen CE, et al. A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Support Care Cancer [PubMed]
23. Wefel JS, et al. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer. 116(14):3348–56. [PubMed]
24. McDonald BC, et al. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat. 123(3):819–28. [PMC free article] [PubMed]
25. Castellon SA, et al. Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004;26(7):955–69. [PubMed]
26. Ferguson RJ, et al. Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol. 2007;25(25):3866–70. [PMC free article] [PubMed]
27. Galimberti D, et al. Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer’s disease. Neurobiol Aging. 2006;27(12):1763–8. [PubMed]
28. Bermejo P, et al. Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett. 2008;117(2):198–202. [PubMed]
29. McNaull BB, et al. Inflammation and Anti-Inflammatory Strategies for Alzheimer’s Disease - A Mini-Review. Gerontology. 2009 [PubMed]
30. Smith PF. Inflammation in Parkinson’s disease: an update. Curr Opin Investig Drugs. 2008;9(5):478–84. [PubMed]
31. Roberts RO, et al. Metabolic syndrome, inflammation, and nonamnestic mild cognitive impairment in older persons: a population-based study. Alzheimer Dis Assoc Disord. 24(1):11–8. [PMC free article] [PubMed]
32. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7(3):192–201. [PMC free article] [PubMed]
33. Villani F, et al. Serum cytokine in response to chemo-radiotherapy for Hodgkin’s disease. Tumori. 2008;94(6):803–8. [PubMed]
34. Pusztai L, et al. Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine. 2004;25(3):94–102. [PubMed]
35. Mills PJ, et al. Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer. Brain Behav Immun. 2008;22(1):98–104. [PMC free article] [PubMed]
36. Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer. 2005;104(4):788–93. [PubMed]
37. Vardy JL, Booth C, Pond GR, Zhang H, Dhillon S, Clarke SJ, Tannock IF. Cytokine levels in patients with colorectal cancer and breast cancer and their relationship to fatigue and cognitive function. Supplement to J Clin Oncol. 2007;18S:9070. Abstract.
38. Vardy J, Dhillon H, Xu W, Dodd A, Renton C, Rourke S, Clarke S, Tannock IF. Cognitive function in colorectal cancer patients: Interim analysis of a longitudinal prospective study; Cognition and Cancer Meeting; 2010; Abstract.
39. Fiocco AJ, et al. COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders. Neurology. 74(16):1296–302. [PMC free article] [PubMed]
40. Collins JS, et al. Association of a haplotype for tumor necrosis factor in siblings with late-onset Alzheimer disease: the NIMH Alzheimer Disease Genetics Initiative. Am J Med Genet. 2000;96(6):823–30. [PubMed]
41. Bertram L, et al. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007;39(1):17–23. [PubMed]
42. Ahles TA, et al. The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psychooncology. 2003;12(6):612–9. [PubMed]
43. Small BJ, Rawson KS, Walsh E, et al. Catechol-O-Methyltransferase (COMT) genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors. Cancer. In Press. [PubMed]
44. Morley KI, Montgomery GW. The genetics of cognitive processes: candidate genes in humans and animals. Behav Genet. 2001;31(6):511–31. [PubMed]
45. McAllister TW, et al. Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments. Curr Psychiatry Rep. 2004;6(5):364–71. [PubMed]
46. Ahles T, Saykin A, McDonald B, Harker Rhodes C, Moore J, Urbanowitz R, Tsongolis G, Tosteson T. Genetics of Cognitive Decline Post Cancer Chemotherapy; Cognition and Cancer Meeting; 2010; Abstract.
47. Miller G. Epigenetics. The seductive allure of behavioral epigenetics. Science. 329(5987):24–7. [PubMed]
48. Pfeilschifter J, et al. Changes in proinflammatory cytokine activity after menopause. Endocr Rev. 2002;23(1):90–119. [PubMed]
49. Greendale GA, et al. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology. 2009;72(21):1850–7. [PMC free article] [PubMed]
50. Paraska K, Bender CM. Cognitive dysfunction following adjuvant chemotherapy for breast cancer: two case studies. Oncol Nurs Forum. 2003;30(3):473–8. [PubMed]
51. Palmer JL, et al. Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls. J Cancer Surviv. 2008;2(4):275–82. [PubMed]
52. Schilder CM, et al. Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. J Clin Oncol. 28(8):1294–300. [PubMed]
53. Klepin H, Mohile S, Hurria A. Geriatric assessment in older patients with breast cancer. J Natl Compr Canc Netw. 2009;7(2):226–36. [PMC free article] [PubMed]
54. Gorin SS, et al. Treatment for breast cancer in patients with Alzheimer’s disease. J Am Geriatr Soc. 2005;53(11):1897–904. [PubMed]
55. Gupta SK, Lamont EB. Patterns of presentation, diagnosis, and treatment in older patients with colon cancer and comorbid dementia. J Am Geriatr Soc. 2004;52(10):1681–7. [PubMed]
56. Goodwin JS, Samet JM, Hunt WC. Determinants of survival in older cancer patients. J Natl Cancer Inst. 1996;88(15):1031–8. [PubMed]
57. Plassman BL, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125–32. [PMC free article] [PubMed]
58. Plassman BL, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med. 2008;148(6):427–34. [PMC free article] [PubMed]
59. Kelley BJ, Petersen RC. Alzheimer’s disease and mild cognitive impairment. Neurol Clin. 2007;25(3):577–609. v. [PMC free article] [PubMed]
60. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94. [PubMed]
61. Extermann M, Aapro M. Assessment of the older cancer patient. Hematol Oncol Clin North Am. 2000;14(1):63–77. viii–ix. [PubMed]
62. Rodin MB, Mohile SG. A practical approach to geriatric assessment in oncology. J Clin Oncol. 2007;25(14):1936–44. [PubMed]
63. Hurria A, et al. Effect of adjuvant breast cancer chemotherapy on cognitive function from the older patient’s perspective. Breast Cancer Res Treat. 2006;98(3):343–8. [PubMed]
64. Chen H, et al. Can older cancer patients tolerate chemotherapy? A prospective pilot study. Cancer. 2003;97(4):1107–14. [PubMed]
65. Extermann M, et al. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol. 2004;49(1):69–75. [PubMed]
66. Hurria A, et al. A prospective, longitudinal study of the functional status and quality of life of older patients with breast cancer receiving adjuvant chemotherapy. J Am Geriatr Soc. 2006;54(7):1119–24. [PubMed]
67. Heck JE, et al. Patterns of Dementia Diagnosis in Surveillance, Epidemiology, and End Results Breast Cancer Survivors Who Use Chemotherapy. J Am Geriatr Soc. 2008 [PubMed]
68. Nelson CJ, et al. Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer. 2008;113(5):1097–106. [PMC free article] [PubMed]
69. Salminen E, et al. Androgen deprivation and cognition in prostate cancer. Br J Cancer. 2003;89(6):971–6. [PMC free article] [PubMed]
70. Green HJ, et al. Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. BJU Int. 2004;93(7):975–9. [PubMed]
71. Mohile SG, et al. Cognitive effects of androgen deprivation therapy in an older cohort of men with prostate cancer. Crit Rev Oncol Hematol. 75(2):152–9. [PMC free article] [PubMed]
72. Chodosh J, et al. Physician recognition of cognitive impairment: evaluating the need for improvement. J Am Geriatr Soc. 2004;52(7):1051–9. [PubMed]
73. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114(512):797–811. [PubMed]
74. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98. [PubMed]
75. Borson S, et al. The Mini-Cog as a screen for dementia: validation in a population-based sample. J Am Geriatr Soc. 2003;51(10):1451–4. [PubMed]
76. DeAngelis LM, Posner JB, editors. Neurologic Complications of Cancer. Side Effects of Chemotherapy. Oxford University Press; New York: 2009.
77. Winocur G, et al. The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice. Pharmacol Biochem Behav. 2006;85(1):66–75. [PubMed]
78. Konat GW, et al. Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis. 2008;23(3):325–33. [PubMed]
79. Foley JJ, Raffa RB, Walker EA. Effects of chemotherapeutic agents 5-fluorouracil and methotrexate alone and combined in a mouse model of learning and memory. Psychopharmacology (Berl) 2008;199(4):527–38. [PMC free article] [PubMed]
80. Mustafa S, et al. 5-Fluorouracil chemotherapy affects spatial working memory and newborn neurons in the adult rat hippocampus. Eur J Neurosci. 2008;28(2):323–30. [PubMed]
81. Janelsins MC, Roscoe JA, Berg MJ, Thompson BD, Gallagher MJ, Morrow GR, Opanashuk LA, Gross RA. IGF-1 Partially Restores Chemotherapy-induced Reductions in Neural Cell Proliferation in Adult C57BL/6 mice. Cancer Invest. 2010;28(2):292–8. [PMC free article] [PubMed]
82. Dietrich J, et al. CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol. 2006;5(7):22. [PMC free article] [PubMed]
83. Han R, et al. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system. J Biol. 2008;7(4):12. [PMC free article] [PubMed]
84. Tangpong J, et al. Adriamycin-induced, TNF-alpha-mediated central nervous system toxicity. Neurobiol Dis. 2006;23(1):127–39. [PubMed]
85. Joshi G, et al. Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug adriamycin: implications for oxidative stress-mediated chemobrain. Neuroscience. 166(3):796–807. [PMC free article] [PubMed]