High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.

The purpose of the present study was to assess patients' anxiety level and information requirement in the preoperative phase. During routine preoperative screening, 320 patients were asked to assess their anxiety and information requirement on a six-item questionnaire, the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Two hundred patients also completed Spielberger's State-Trait Anxiety Inventory (STAI-State). Patients were able to complete the questionnaire in less than 2 min. On factor analysis, two factors emerged clearly: anxiety and the need for information. The anxiety scale correlated highly (0.74) with the STAI-State. It emerged that 32% of the patients could be considered as "anxiety cases" and over 80% of patients have a positive attitude toward receiving information. Moreover, results demonstrated that 1) women were more anxious that men; 2) patients with a high information requirement also had a high level of anxiety; 3) patients who had never undergone an operation had a higher information requirement than those who had. The APAIS can provide anesthesiologists with a valid, reliable, and easily applicable instrument for assessing the level of patients' preoperative anxiety and the need for information.

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The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract-based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H-MRS) in the left centrum semiovale (white matter) showed a reduction of N-acetylasparate/creatine indicative of axonal injury. Voxel-based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H-MRS only in the chemotherapy group. These results converge to suggest that high-dose adjuvant chemotherapy for breast cancer is associated with long-term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment.