RESUMO
Cancer-related cognitive impairment has a significant impact on the quality of life and perceived cognitive ability of breast cancer patients and frequently affects attention, working memory, and executive function. Several interventional approaches to treat these deficits have been studied, including web-based cognitive training, but methods and timing in relation to cancer treatment are heterogeneous. Only few interventions start early after primary breast cancer treatment, a time when many patients report the greatest impairments in quality of life and cognition. In this randomized controlled pilot study, 31 breast cancer survivors with subjective cognitive deficits and a mean post-treatment duration of 6.6 months (SD = 9.3) were assigned to either 14 weeks of a web-based cognitive training program (training group, n = 16) or a control group (n = 15). All patients underwent detailed neuropsychological assessment, evaluation of patient-reported outcomes (PROMs), and neurological examination before (baseline, T1) and after (follow-up, T2) the intervention. Longitudinal (T1 vs. T2) and cross-sectional (T2) cognitive performance was assessed for both groups. Overall cognitive impairment significantly improved in the training group following training (56% vs 25%; p = 0.03, Phi = 0.51), but not in the control group (73% vs. 73%; p = 1) in the longitudinal analysis (T1 vs. T2). Specifically, the training group showed statistically significant improvement of executive functions (p = 0.004, Phi = 0.32). No effects of training on subjective cognitive deficits or PROMs were observed. Comparing cross-sectional cognitive performance at follow-up (T2), the training group showed a significantly lower rate of cognitive impairment overall (p = 0.007, Phi = 0.48) and a better cognitive performance for executive function (p = 0.04, Phi = 0.32) compared to the control group. In this prospective pilot study, web-based cognitive training was efficacious in improving overall cognitive performance and executive function. Importantly, this study investigated a web-based cognitive training for the immediate post-treatment phase, when up to 75% of breast cancer patients experience cognitive decline. These results indicate that cognitive training may improve neuropsychological outcomes for patients with breast cancer.
RESUMO
Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid "route following." Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.