Rugo HS, Ahles T.
The impact of adjuvant therapy for breast cancer on cognitive function: current evidence and directions for research.

Semin Oncol. 2003 Dec;30(6):749-62. Review.
PMID: 14663776 [PubMed – indexed for MEDLINE]

Available evidence supports the hypothesis that adjuvant chemotherapy for breast cancer can produce cognitive deficits, and that these deficits may have a significant impact on patients’ quality of life. Studies have generally compared the results of a variety of cognitive measures performed following treatment to standardized population-based norms or to cancer patients who received local therapy, rather than to the individual’s baseline level of functioning. Several longitudinal studies are in progress or in the planning stages to better quantify and understand the incidence and impact of cognitive effects of adjuvant chemotherapy, and to identify possible susceptibility factors in subgroups. Although the neurocognitive changes appear to be subtle, there may be enough data to consider discussing the possibility of cognitive dysfunction as an adverse effect when assessing the risks and benefits of adjuvant chemotherapy. Likewise, as the aromatase inhibitors are increasingly given to larger numbers of women in the adjuvant setting, it will be important to understand the cognitive impact of estrogen deprivation. Finally, there is interest in examining supportive pharmacologic or behavioral measures that might prevent or decrease cognitive effects in this setting. Herein, the data on cognitive changes associated with chemotherapy for breast cancer, current and future research directions, as well as possible treatments are reviewed.

bulletDepartment of Medicine, University of California Comprehensive Cancer Center, San Francisco 94115, USA


Cunningham RS.
Anemia in the oncology patient: cognitive function and cancer.

Cancer Nurs. 2003 Dec;26(6 Suppl):38S-42S.

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.

bullet Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901, USA.
Tchen N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, Clemons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF.
Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer.

J Clin Oncol. 2003 Nov 15;21(22):4175-83.
PMID: 14615445 [PubMed – indexed for MEDLINE]

PURPOSE: There is evidence that cognitive dysfunction, fatigue, and menopausal symptoms may occur in women receiving adjuvant chemotherapy for breast cancer. Here, we determine their incidence and severity, and interrelationships between them and quality of life. PATIENTS AND METHODS: In this study, 110 women receiving adjuvant chemotherapy each nominated a female relative, friend, or neighbor (matched by age) as a control; 100 eligible matched pairs were evaluated. Patients and controls completed the following assessments: the High-Sensitivity Cognitive Screen, and the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life scale with subscales for fatigue (FACT-F) and endocrine symptoms (FACT-ES). They also performed tests of attention and reaction time. RESULTS: Patients and controls were well matched for age and level of education. There was a higher incidence of moderate or severe cognitive impairment in the patient group (16% v 4%; P =.008). Patients experienced much more fatigue than controls (median FACT-F scores, 31 v 46; P <.0001) and more menopausal symptoms (median FACT-ES scores, 58 v 64; P <.0001). Self-reported quality of life of the patients was poorer than for controls, especially in physical and functional domains (median FACT-G scores, 77 v 93; P <.0001). There was strong correlation between fatigue, menopausal symptoms, and quality of life (P <.0001 for each pair), but none were significantly associated with the presence of cognitive dysfunction. CONCLUSION: Adjuvant chemotherapy causes cognitive dysfunction, fatigue, and menopausal symptoms in women with breast cancer. Priority should be given to the study of strategies that might reduce these toxic effects.

bulletPrincess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada.


O’Shaughnessy, JA.
Chemotherapy induced cognitive dysfunction:  a clearer picture

Clin Breast Cancer. 2003 Nov;4 Suppl 2:S89-94. Review.
PMID: 14705598 [PubMed – indexed for MEDLINE]

Chemotherapy-associated cognitive dysfunction occurs in a subset of patients treated with adjuvant chemotherapy. Recent data suggest that development of chemotherapy-related anemia predisposes patients to cognitive dysfunction. Endogenous erythropoietin (EPO) is well recognized for its central role in erythropoiesis, and recombinant human EPO (epoetin alfa) is established as a safe and effective treatment for chemotherapy-related anemia. Treatment with epoetin alfa also improved health-related quality of life in anemic cancer patients undergoing chemotherapy, and several controlled studies have documented increases in quality-of-life scores correlated with increases in hemoglobin. Erythropoietin also plays a role in neuroprotection, presumably by activation of antiapoptotic genes. Erythropoietin and its receptor are expressed in neural cells of the human brain, and their expression is upregulated after hypoxic or ischemic injury. In animal models, systemic administration of epoetin alfa protects against such neural injury. Ongoing and future studies will determine whether epoetin alfa can provide neuroprotection with respect to the development of cognitive dysfunction in patients undergoing adjuvant chemotherapy treatment for breast cancer.

bulletBaylor Sammons Cancer Center, US Oncology, 3535 Worth Street, Collins Building 5th Floor, Dallas, TX 75246, USA. joyce.o’


Morse R, Rodgers J, Verrill M, Kendell K.
Neuropsychological functioning following systemic treatment in women treated for breast cancer: a review.

Eur J Cancer. 2003 Nov;39(16):2288-97. Review.
PMID: 14556919 [PubMed – indexed for MEDLINE]

The aim of this review was to evaluate the effect of treatment and illness-related factors on neuropsychological functioning in women treated for breast cancer. Eight studies were identified examining neuropsychological test performance following systemic treatment. Six of the eight studies suggest that neuropsychological functioning may be impaired following treatment. However, there are a number of important methodological issues which limit interpretation of these results. Therefore, it is unclear whether neuropsychological outcome differs according to a range of treatment, biomedical and psychological factors. Larger samples with longitudinal follow-up are required in order to examine the treatment-related factors that best predict cognitive deficits.

bulletDepartment of Clinical Psychology, School of Neurology, Neurobiology and Psychiatry, Ridley Building, University of Newcastle, NE1 7RU, Newcastle upon Tyne, UK.


Waldstein SR, Elias MF.
Introduction to the special section on health and cognitive function.

Health Psychol. 2003 Nov;22(6):555-8.
PMID: 14640851 [PubMed – indexed for MEDLINE]

Numerous factors related to health and diseases have been studied in relation to cognitive function. It has been shown that across the life span, systemic medical diseases can negatively impact cognitive function. Factors that influence the development of medical diseases, such as poor health habits, biological risk factors, hormones, genetic factors, exposure to environmental toxins, and certain treatments for disease, can also have an adverse effect on cognitive function. Conversely, factors such as high levels of education, good health habits, and some treatments for disease can be protective. Included in this special section are 6 empirical articles that examine the relation of health or disease to cognitive function.

bulletDepartment of Psychology, University of Maryland, Baltimore County, and Geriatric Research Educational and Clinical Center, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21250, USA.


O’Shaughnessy J.
Chemotherapy-related cognitive dysfunction in breast cancer.

Semin Oncol Nurs. 2003 Nov;19(4 Suppl 2):17-24. Review.
PMID: 14702917 [PubMed – indexed for MEDLINE]

OBJECTIVES: To provide an overview of chemotherapy-related cognitive dysfunction in breast cancer survivors, focusing on its pathophysiology, risk factors, assessment, and management. DATA SOURCES: Published biomedical literature. CONCLUSION: Chemotherapy-related cognitive dysfunction in patients with breast cancer is multifactorial and possibly related to anemia or a direct effect of chemotherapy on brain function. Clinical observation and subjective reports are useful assessments. Therapies directed at alleviating or preventing cognitive deficits are being investigated. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are important in monitoring cognitive function in patients with breast cancer receiving chemotherapy. Nurses who are aware of the risks, assessment, and management of cognitive impairment are better able to discuss these issues with patients and caregivers.

bulletBaylor Sammons Cancer Center, US Oncology, Dallas, TX, USA.


Saykin AJ, Ahles TA, McDonald BC.
Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.

Semin Clin Neuropsychiatry. 2003 Oct;8(4):201-16. Review.
PMID: 14613048 [PubMed – indexed for MEDLINE]

Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.

bulletBrain Imaging Laboratory, Dartmouth Medical School, Lebanon, NH 03756, USA.


Salminen E, Portin R, Korpela J, Backman H, Parvinen LM, Helenius H, Nurmi M.
Androgen deprivation and cognition in prostate cancer.

Br J Cancer. 2003 Sep 15;89(6):971-6.
PMID: 12966411 [PubMed – indexed for MEDLINE]

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P=0.035; delayed, P<0.001), and in semantic memory (P=0.037). In QoL, impairment in physical function was observed. Androgen deprivation of 12 months appears to be associated with preserved cognitive functioning, although physical impairment occurs. These results have implications for counseling and psychosocial support of patients in the context of treatment options in PC.

bulletDepartment of Oncology, Turku University Hospital, Kiinamyllynkatu 4-8, Fin-20520 Turku, Finland.


Shilling V, Jenkins V, Fallowfield L, Howell T.
The effects of hormone therapy on cognition in breast cancer.

J Steroid Biochem Mol Biol. 2003 Sep;86(3-5):405-12. Erratum in: J Steroid Biochem Mol Biol. 2005 Jun;96(1):93.
PMID: 14623538 [PubMed – indexed for MEDLINE]

The use of hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects. Several regions of the brain, important in memory and cognition, are rich in oestrogen receptors. As a result, the long-term use of anti-oestrogens may have potential consequences for cognition. This project aims to establish whether significant cognitive deficit exists in women receiving hormone therapy for breast cancer and to develop a cognitive package that is sensitive to the potential effects of oestrogen deficiency on cognition. Cognitive assessments measured a range of memory and attention functions in patient and control groups to identify whether cognitive impairment, if apparent, occurs at a widespread or function specific level. Ninety-four patients from the anastrozole, tamoxifen and combined (ATAC) trial and 35 non-cancer controls were assessed. Groups did not differ significantly in age or estimated full-scale intelligence. The patient group did not differ from controls on measures of working memory, attention and visual memory but was significantly impaired compared to the control group on measures of verbal memory (P=0.026) and processing speed (P=0.032). Cognitive performance in the patient group was not significantly related to length of time on trial or measures of psychological morbidity. As more and more hormonal agents are used in clinical trials of both adjuvant and preventive settings it is of vital importance that any potentially deleterious effects on cognitive function are measured adequately. Preliminary results from this study suggest that anti-oestrogen therapy may cause a specific deficit in verbal memory that corroborates the links between oestrogen levels and verbal memory often reported in studies of the cognitive benefits of hormone replacement therapy.

bulletPsychosocial Oncology Group (Cancer Research UK), Brighton and Sussex Medical School, University of Sussex, Falmer, East Sussex, BN1 9QG, UK.


Ahles TA, Saykin AJ, Noll WW, Furstenberg CT, Guerin S, Cole B, Mott LA.
The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy.

Psychooncology. 2003 Sep;12(6):612-9.
PMID: 12923801 [PubMed – indexed for MEDLINE]

PURPOSE: The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles. PATIENTS AND METHODS: Long-term survivors (mean=8.8+/-4.3 years post-treatment) of breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29, age=55.8+/-11.6) who had been treated with standard-dose chemotherapy completed a standardized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N=17) or absence (N=63) of at least one epsilon 4 allele of APOE. RESULTS: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ), indicated that survivors with at least one epsilon 4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon 4 allele. No group differences were found on depression, anxiety, or fatigue. CONCLUSIONS: The results of this study provide preliminary support for the hypothesis that the epsilon 4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline. Copyright 2003 John Wiley & Sons, Ltd.

bulletDepartment of Psychiatry and Center for Psycho-Oncology Research, USA.


Caffo O, Amichetti M, Ferro A, Lucenti A, Valduga F, Galligioni E.
Pain and quality of life after surgery for breast cancer.

Breast Cancer Res Treat. 2003 Jul;80(1):39-48.
PMID: 12889597 [PubMed – indexed for MEDLINE]

BACKGROUND: In breast cancer (BC) patients, conservative surgery (CS) followed by irradiation or immediate breast reconstruction (IBR) after modified radical mastectomy (MRM) has been proposed in the attempt to avoid the negative impact of MRM on feminine body image. Regardless of the type of operation, BC patients may feel pain even without recurrent disease with poor adjustment in terms of quality of life (QL). METHODS: We adopted a questionnaire comprising the short form of the McGill Pain questionnaire, and a previously validated questionnaire able to identify four subscales exploring physical well-being, physical autonomy, relational life and psychological well-being. The questionnaire was mailed in 1999 to a consecutive series of 757 (CS: 481 cases; MRM + IBR with skin expander: 93 cases; MRM: 183 cases) disease-free patients treated for BC between March 1995 and March 1998. RESULTS: The final analysis assessed the data relating to 529 patients who underwent axillary dissection. Pain was reported by 39.7% of women with higher incidence in patients who underwent CS than in those who underwent MRM +/- IBR, but this difference did not reach statistical significance (p = 0.07). The only statistically significant difference (p < 0.05) between the surgical groups was the pain appearance that occurred earlier in the CS patients and later in the MRM + IBR patients. No other differences were observed. The women with pain had significantly worse QL scores on all of the subscales than those without. CONCLUSION: Pain after surgery for BC distress almost one-third of patients, regardless of the type of treatment, and had a negative effect on patients’ QL. The different surgical procedures may marginally influence the quantitative characteristics of pain.

bulletDepartment of Medical Oncology, Largo Medaglie d’Oro, Santa Chiara Hospital, Trento, Italy.


Denison U, Baumann J, Peters-Engl C, Samonigg H, Krippl P, Lang A, Obermair A, Wagner H, Sevelda P.
Incidence of anaemia in breast cancer patients receiving adjuvant chemotherapy.

Breast Cancer Res Treat. 2003 Jun;79(3):347-53.
PMID: 12846419 [PubMed – indexed for MEDLINE]

Anaemia is frequent in breast cancer patients but often remains undiagnosed and untreated. To determine the incidence of anaemia a prospective survey of primary non-metastatic breast cancer patients who received at least four cycles of adjuvant, non-platinum multi-agent chemotherapy was conducted at 47 centres in Austria. Two hundred and forty seven patients were prospectively included between October 1999 and December 1999. Haemoglobin (Hb) levels were determined after surgery and prior to each cycle of chemotherapy. Treatment of anaemia (blood transfusion or epoetin alfa) during the observation period was at the physician’s discretion. For the purpose of this study, patients were considered to be anaemic if their Hb was below 12 g/dl. At baseline (after surgery and before the first cycle of chemotherapy), 28.7% of all patients were anaemic. The only significant differentiating factor was the type of surgery. 37.9% of patients who underwent mastectomy were anaemic, whereas only 22.8% of patients who underwent breast conserving surgery were anaemic. Forty two percent of 176 patients with a Hb level of > or = 12 g/dl at baseline developed anaemia during adjuvant chemotherapy. The only factor that significantly influenced the development of anaemia during chemotherapy was the Hb level at baseline. The total incidence of anaemia in patients with primary breast cancer who underwent surgery followed by adjuvant multi-agent chemotherapy was 58.7%. Forty nine patients (20.2%), 48 patients (19.2%) and 48 patients (19.2%) showed a decrease in Hb levels by 1 g/dl, 1-2 g/dl and > 2 g/dl, respectively. Only 18.6% of the patients who were found to be anaemic received anaemia treatment. The two most important factors for developing anaemia are the kind of surgery and the Hb level prior to chemotherapy.

bulletDepartment of Obstetrics & Gynecology, General Hospital Lainz, Vienna, Austria.


Carpentieri SC, Waber DP, Pomeroy SL, Scott RM, Goumnerova LC, Kieran MW, Billett AL, Tarbell NJ.
Neuropsychological functioning after surgery in children treated for brain tumor.

Neurosurgery. 2003 Jun;52(6):1348-56; discussion 1356-7.
PMID: 12762880 [PubMed – indexed for MEDLINE]

OBJECTIVE: To describe the neuropsychological functioning of children treated with surgery only for localized brain tumors in Dana-Farber Cancer Institute Protocol 92-077. Subsequent reports will describe the neuropsychological functioning of children treated with surgery and stereotactic radiation therapy on Dana-Farber Cancer Institute 92-077. METHODS: The intellectual functioning of 106 patients was evaluated within 3 months after surgery. An in-depth assessment of the neuropsychological functioning, including an impairment index, was conducted for a subset of 77 school-age children (6-16 yr old) across six functional domains. Descriptive statistics were generated; binomial distribution analyses were performed to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. The impairment index assessed whether poor performance was attributable to a few children or reflected the performance of the cohort as a whole. RESULTS: Although the Full Scale IQ was within normative expectations, the Verbal IQ was higher than the Performance IQ with 45% of individuals showing a significant discrepancy (P < 0.01) between these scales. There was an increased prevalence of poor performance for measures of motor output, verbal memory, and visuospatial organization. The distribution of the impairment index indicated moderate impairment across the school-age cohort rather than severe impairment in a few patients. CONCLUSION: The results document a moderate level of neuropsychological morbidity among children with brain tumors before stereotactic radiation therapy, presumably referable to the tumor itself and the surgery. The extent to which stereotactic radiation therapy may increase this burden will be assessed in follow-up studies evaluating the longitudinal neuropsychological data.

bulletDivision of Psychology, Department of Psychiatry, Children’s Hospital, Boston, MA, USA.


Ferguson RJ, Ahles TA.
Low neuropsychologic performance among adult cancer survivors treated with chemotherapy.

Curr Neurol Neurosci Rep. 2003 May;3(3):215-22. Review.
PMID: 12691626 [PubMed – indexed for MEDLINE]

Decline in neuropsychologic test performance following adjuvant chemotherapy for various types of cancer has gained much research attention over the past decade. From available data, about one fourth to one third of individuals undergoing systemic chemotherapy exhibit measurable decrements in performance of standard tests of cognitive function. Many cancer survivors report that cognitive problems interfere with function and compromise quality of life. However, these declines appear subtle and there are little available longitudinal data examining pre- to post-treatment cognitive change. Further, there is little available evidence identifying the causes of cognitive decline. This paper reviews current literature on low neuropsychologic performance following systemic chemotherapy and hypotheses on the causes of cognitive symptoms following chemotherapy. Future research directions, with emphasis on longitudinal research design as well as treatment implications, are discussed.

bulletDepartment of Psychiatry & Center for Psycho-Oncology Research, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.


Paraska K, Bender CM.
Cognitive dysfunction following adjuvant chemotherapy for breast cancer: two case studies.

Oncol Nurs Forum. 2003 May-Jun;30(3):473-8.
PMID: 12719746 [PubMed – indexed for MEDLINE]

PURPOSE/OBJECTIVES: To describe the cognitive dysfunction experienced by two women after they received adjuvant chemotherapy for breast cancer and to discuss the potential role of changes in reproductive status and depression in the development of cognitive dysfunction. DATA SOURCES: Journal articles, research data, and clinical experience. DATA SYNTHESIS: Following chemotherapy, 17%-50% of women with breast cancer experience cognitive dysfunction that may include decrements in memory, attention, and psychomotor efficiency. One mechanism that may contribute to cognitive dysfunction involves changes in reproductive status resulting from chemotherapy. Additionally, the presence of depression may confound the experience of cognitive dysfunction. CONCLUSIONS: A comprehensive description of cognitive dysfunction and improved understanding of the interrelationships among cognitive dysfunction, reproductive hormone levels, and depression in women with breast cancer receiving adjuvant chemotherapy may hasten the development of interventions for the management of cognitive dysfunction. IMPLICATIONS FOR NURSING: Nurses should teach women with breast cancer and their families about the potential for cognitive dysfunction after chemotherapy so the problem can be recognized and interventions can be implemented to help women compensate for the dysfunction.

bulletSchool of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.


Fliessbach K, Urbach H, Helmstaedter C, Pels H, Glasmacher A, Kraus JA, Klockgether T, Schmidt-Wolf I, Schlegel U.
Cognitive performance and magnetic resonance imaging findings after high-dose systemic and intraventricular chemotherapy for primary central nervous system lymphoma.

Arch Neurol. 2003 Apr;60(4):563-8.
PMID: 12707070 [PubMed – indexed for MEDLINE

BACKGROUND: Long-term neurotoxicity is a frequent complication of combined radiotherapy and chemotherapy in patients with primary central nervous system lymphoma. Treatment protocols without radiotherapy have been implemented to avoid this; however, little detailed neuropsychologic and neuroradiologic data exist to assess the frequency of long-term treatment sequelae in this patient group. OBJECTIVE: To determine whether a polychemotherapy regimen based on high-dose methotrexate results in cognitive impairment and/or changes detectable by magnetic resonance imaging of the brain during long-term follow-up. PATIENTS AND METHODS: Twenty patients with histologically proven primary central nervous system lymphoma were treated with a novel chemotherapy protocol that included systemic and intraventricular administration of methotrexate and cytarabine (ara-C). Standardized neuropsychologic testing and magnetic resonance imaging investigations were performed prior to therapy and prospectively during a median follow-up period of 36 months (range, 21-69 months). RESULTS: Ten patients achieved durable remissions without relapse for more than 1 year after completion of chemotherapy. There was no gross cognitive decline in any of these patients during the follow-up period. In contrast, magnetic resonance imaging revealed therapy-induced white matter changes in 5 of these patients. CONCLUSIONS: We conclude that chemotherapy alone is associated with a low risk of long-term neurotoxicity in primary central nervous system lymphoma. Methotrexate-induced white matter lesions detectable on magnetic resonance imaging are not inevitably associated with significant cognitive decline.

bulletDepartment of Neurology, University of Bonn, Bonn, Germany.


Friedman MA, Meyers CA, Sawaya R.
Neuropsychological effects of third ventricle tumor surgery.

Neurosurgery. 2003 Apr;52(4):791-8; discussion 798.
PMID: 12657174 [PubMed – indexed for MEDLINE]

OBJECTIVE: This study assessed the neuropsychological outcome of patients after surgical treatment for third ventricle brain tumors. Neuropsychological consequences of surgical intervention can have a major impact on patients’ quality of life and therefore have important implications for treatment planning. METHODS: A retrospective analysis of 33 patients’ neuropsychological data was performed. All patients received a comprehensive neuropsychological evaluation after treatment for a primary brain tumor in the third ventricular region. Twenty-six patients underwent surgery, 14 via the transcallosal approach and 12 via a subfrontal, left transcortical, right pterional, or infratentorial supracerebellar approach. Seven patients were not treated by surgical intervention. RESULTS: There was a significantly elevated frequency of cognitive impairment relative to normative values in memory, executive functioning, and fine manual speed and dexterity. There were no differences in mean neuropsychological scores between patients who underwent surgery and those who did not. There were no differences in mean performance on the basis of surgical approach, tumor infiltration, or history of cranial irradiation. Repeated measures data available for two patients revealed memory impairment before and after surgery, and one patient experienced major improvement after surgery on a measure of mental flexibility and problem solving. CONCLUSION: Patients with third ventricle tumors are at risk for developing impairments in memory, executive function, and fine manual speed and dexterity, which are domains associated with frontal subcortical functions. In the current study, different types of treatment were not associated with differential cognitive sequelae, and surgical intervention did not account for cognitive deficits.

bulletThe Brain and Spine Center, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.


Hahn CA, Dunn RH, Logue PE, King JH, Edwards CL, Halperin EC.
Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors.

Int J Radiat Oncol Biol Phys. 2003 Mar 15;55(4):992-9.
PMID: 12605978 [PubMed – indexed for MEDLINE]

PURPOSE: To identify the characteristics of adult patients with newly diagnosed primary brain tumors associated with identifiable deficits in neuropsychologic function to target interventions to improve function and quality of life (QOL). MATERIALS AND METHODS: Adult patients with newly diagnosed primary brain tumors and their caregivers were enrolled and underwent a battery of standardized neuropsychologic tests, allowing for qualitative and quantitative assessment and sensitive to the effects of the brain tumor, QOL, or caregiver stress. RESULTS: We enrolled 68 patients with no prior radiotherapy. Patients with left hemisphere tumors reported significantly more memory problems and depressive symptoms. They also exhibited poorer attention and were more distractible, with poorer verbal fluency and poorer verbal learning. Patients with glioblastoma multiforme demonstrated poorer psychomotor speed and visual tracking than patients with non-glioblastoma multiforme histologic features. Patients and caregivers perceived QOL in a similar fashion, with significant correlation between patient and caregiver on hope testing and general QOL on the Linear Analog Self-Assessment Scale. CONCLUSIONS: Patients with left hemisphere tumors and glioblastoma multiforme histologic features demonstrated testable differences in neuropsychologic function and QOL that may be amenable to improvement with medical therapy or tailored rehabilitation programs. Caregiver assessments can predict patient QOL, which may be useful in patients with declining status.

bulletDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.


Fuh JL, Wang SJ, Lu SR, Juang KD, Lee SJ.
Alterations in cognitive function during the menopausal transition.

J Am Geriatr Soc. 2003 Mar;51(3):431-2. No abstract available.
PMID: 12588594 [PubMed – indexed for MEDLINE]


Gottschalk LA, Holcombe RF, Jackson D, Bechtel RJ.
The effects of anticancer chemotherapeutic drugs on cognitive function and other neuropsychiatric dimensions in breast cancer patients.

Methods Find Exp Clin Pharmacol. 2003 Mar;25(2):117-22.
PMID: 12731457 [PubMed – indexed for MEDLINE]

This preliminary study aimed to apply a novel computerized measure derived from the content analysis of 5-min speech samples from patients with breast cancer to measure cognitive impairment and other neuropsychiatric dimensions during the course of anticancer chemotherapeutic treatment. Since such patients are often administered other pharmacological agents to alleviate their symptoms in addition to anticancer chemotherapeutic agents, another aim was to try to distinguish the mental effects of the anticancer drugs from the effects of any other drugs administered. Before and during the course of their anticancer chemotherapy, 12 breast cancer patients gave 5-min verbal samples, elicited by purposely ambiguous instructions, to talk about any personal life experiences. The recorded verbal samples were scored by a computer program (PCAD 2000) to measure the magnitude of cognitive impairment and other relevant neuropsychiatric dimensions. All of the pharmacological agents administered to the patients were recorded. The computer program automatically compared the scores derived from each verbal sample to already established norms to determine whether each score was within normal limits or one to three standard deviations from the norms. Significantly elevated Cognitive Impairment Scale scores were found in the verbal samples of 9 of the 12 patients. All patients had instances of elevated Health/Sickness Content Analysis Scale scores as well as frequent significantly elevated scores in shame anxiety and in death anxiety. In the Quality of Life Content Scale, the scores were uniformly low, ranging from +1.64 to -9.11. Further studies are being carried out to determine which patients are especially susceptible to cognitive impairment under these treatment conditions.

bulletDepartment of Psychiatry, College of Medicine, University of California, Irvine, USA.


Phillips KA, Bernhard J.
Adjuvant breast cancer treatment and cognitive function: current knowledge and research directions.

J Natl Cancer Inst. 2003 Feb 5;95(3):190-7. Review.
PMID: 12569140 [PubMed – indexed for MEDLINE]

Evidence is mounting that potentially curative systemic adjuvant therapy for early-stage breast cancer may result in cognitive impairment. Five published studies have investigated cognitive function in this setting, and the consistent results of all five studies suggest an adverse effect of adjuvant chemotherapy. These studies are reviewed with particular attention to their methodologic limitations. For example, all five studies used cross-sectional designs, none controlled for possible confounding hormonal factors, and three examined patients who had not received a uniform chemotherapy regimen. The potential roles of chemotherapy-induced menopause and of adjuvant hormonal therapy in cognitive impairment are also discussed. Priorities for future research include confirmation of an effect of adjuvant chemotherapy in a study with a longitudinal design, closer examination of the potential contribution of hormonal factors, and similar studies on the effect of adjuvant therapy on cognitive function in other cancer types. If an effect of systemic adjuvant therapy on cognitive function is confirmed, such an effect will have implications for informed consent. It may also result in incorporation of objective measures of cognition in clinical trials of adjuvant therapy and in the investigation of preventive interventions that might minimize the impact of cognitive dysfunction after cancer treatment.

bulletDepartment of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, St. Andrew’s Place, East Melbourne, Victoria, Australia.


George AP, Kuehn SM, Vassilyadi M, Richards PM, Parlow SE, Keene DL, Ventureyra EC.
Cognitive sequelae in children with posterior fossa tumors.

Pediatr Neurol. 2003 Jan;28(1):42-7.
PMID: 12657419 [PubMed – indexed for MEDLINE]

Late effects of radiotherapy on intellectual functioning have been well documented in children treated for posterior fossa tumors. Other aspects of cognitive functioning, such as memory, have not been adequately assessed in this population. This retrospective review reports on 15 children diagnosed with medulloblastoma or cerebellar astrocytoma who were administered a norm-referenced standardized test of memory functioning (i.e., Wide Range Assessment of Memory and Learning) an average of 3.5 years after treatment. Analyses revealed that sample means of IQ and memory were significantly lower than those of the normative population. No significant differences were found between the verbal and nonverbal IQ, or verbal and visual memory. Age at diagnosis accounted for a significant proportion of variability in the intelligence ratings but not in the memory indexes. The IQ scores of children less than 6 years of age at diagnosis were significantly lower than those of children diagnosed when over 6 years of age. Given the substantial variability within the older age group, there was insufficient power to detect true differences between memory index means for children by age at diagnosis. Follow-up assessments over 5 years may better identify the long-term effects of radiotherapy on memory functioning

bulletMental Health Patient Service Unit, Children’s Hospital of Eastern Ontario, Ottawa, Canada.