Cognitive disturbances linked to cancer and its treatments

Responsible : Bénédicte Giffard

Cancer patients undergoing chemotherapy frequently complain of cognitive deficits. These deficits, while subtle, can have a genuinely negative impact on quality of life. They are sometimes observed as soon as the diagnosis has been announced, as well as in the wake of other categories of treatment, such as targeted therapies (Morel N, Eustache F, Lange M, Joly F, Giffard B (2010). L’impact du cancer et de ses traitements sur les fonctions cognitives : l’exemple du cancer du sein. Rev Neuropsychol 2 : 1-5). In order to describe these disturbances and gain a clearer understanding of them, we will carry out four longitudinal investigations. The first of these (COGAGE) will attempt to assess the impact of cognitive disturbances induced by chemotherapy on quality of life and fatigue, and see how they change over time (one pre-treatment assessment and four post-treatment ones: at the end of treatment, then 6, 12 and 24 months later). It will involve 200 patients receiving adjuvant therapy for breast cancer and aged over 65 years, for as most clinical trials have been conducted with young patients, there are very few data on the side effects of chemotherapy in older adults.

The second investigation (CANMEM) will be used to gain a more accurate idea of the psychological and pathophysiological mechanisms behind patients’ memory disorders. This longitudinal study (pre-treatment, end of treatment, one year after the end of treatment) will include 30 female patients aged 45-75 years undergoing adjuvant chemotherapy for nonmetastatic breast cancer and 30 healthy matched controls. A resting-state fMRI protocol will be implemented to assess the pathophysiological processes involved, enabling us to describe modifications in the default network and show whether or not there is any link between these modifications and possible memory problems. Task-activated fMRI will provide an opportunity for studying the role of the self in an episodic memory task requiring the participant’s direct and personal involvement (see IMAP protocol ).

In recent years, a new class of treatments, called targeted therapies, especially angiogenesis inhibitors, has shown itself to be particularly effective and become the treatment of choice for kidney cancer. However, as angiogenesis inhibitors can cross the blood-brain barrier, patients themselves frequently report cognitive deficits and fatigue. And yet these symptoms have never been the subject of a specific study. Our third investigation (COGANGIO) will therefore look at 120 patients aged over 18 years receiving angiogenesis inhibitors for metastatic kidney cancer (one pre-treatment assessment and three after the start of the treatment, at 3, 6 and 12 months). The three above-mentioned studies will use specific tests to assess various cognitive functions, along with anxious-depressive factors, fatigue and patients’ quality of life.

The fourth and final investigation is intended to improve current understanding of the relationship between performances on neuropsychological tests and subjective complaints from patients after a course of adjuvant treatment. Many studies have failed to find any significant correlation between these two measures, with patients generally perceiving their cognitive deficits to be greater than measurements yielded by the neuropsychological tests would indicate. There are probably many factors accounting for this absence of any attested link: 1) methodological factors, 2) psychoaffective factors (anxiety/depression and fatigue), and 3) metacognition. Although the latter has often been assessed in other pathologies to measure its impact on cognitive disorders, it has never been tested in cancer patients, even though it is an extremely sensitive measure for assessing and understanding patients’ complaints and seeing how far they correspond to actual performances. The study will therefore consist in measuring and explaining the correspondence between the cognitive disturbances perceived by cancer patients and their objective scores, by administering metacognition tasks, controlling for fatigue and anxious-depressive factors, as well as for the effect of the treatment, and implementing a longitudinal design.

Collaborations : Florence Joly, CLCC Caen and Cancéropôle Nord-Ouest.