Aging is associated with cognitive and functional decline and comorbidities that may have a significant impact on the patient’s autonomy. These alterations may be exacerbated by cancer and the toxicity of antitumoral agents, and functional decline is associated with a worse prognosis. Initial cognitive functioning and functional status could thus influence the choice of treatment.

The impact of cancer and chemotherapy on cognition and quality of life is thought to depend on several factors including baseline cognitive functioning, which is expected to be lower in older patients than in younger ones [32]. Little is known about the effect of treatment on the cognitive functioning of older patients [33] or whether chemotherapy-associated cognitive alterations affect an older patient’s ability to perform daily activities.

Although there is no data available in ovarian cancer patients, the first longitudinal study on cognitive assessment in older patients with neuropsychological tests was conducted among breast cancer patients treated by adjuvant chemotherapy (n = 28, mean age 71 ± 5) [33]. Thirty-nine percent of patients experienced a decline in cognitive performance within the 6 months following the start of chemotherapy (50 % had no change and 11 % improved). Furthermore, cancer survivors were also concerned by cognitive impairments: breast cancer survivors, who remained disease-free for more than one or two decades (mean age 73 ± 5.1 and 64 ± 6.4, respectively), performed worse on average than population controls [13, 34]. A similar pattern of differences in neuropsychological performances was found between groups to the detriment of the patient groups having undergone long-term chemotherapy. The impairment of executive functioning and psychomotor speed, working memory and attention, immediate and delayed verbal memory, and information processing speed [13] was in favor of dysfunctions involving the fronto-subcortical brain regions. Overall, the low number of studies performed in elderly patients suggests that cognitive disturbances affect the same functions as in younger patients. Previous cancer treatment may therefore exacerbate cognitive dysfunctions associated with age-related brain changes.

On the other hand, studies using cognitive screening tests like the Mini Mental State Examination or MMSE [35] did not find any cognitive impairment after cancer treatment. Cognitive impairments induced by cancer treatment are subtle and screening tests did not appear sensitive enough to detect them. However, even a small decline in elderly patients may have an important impact on their daily life.

Many mechanisms are involved in cognitive deficits particularly in elderly cancer patients (Fig. 2.1 [36]). Aging, neurodegeneration, biological processes underlying cancer, the impact of cancer treatments, and cognitive decline appear to be linked, leading to the phase shift hypothesis, i.e., that cancer treatments may accelerate the aging process. According to this hypothesis, age-associated decline in cancer patients is not only parallel but is greater than that of older adults with no cancer history. An additional hypothesis, which does not exclude the latter, postulates that only vulnerable populations exhibit the accelerated aging pattern [5].

Some factors closely related to aging such as comorbidities (mainly cardiovascular disease, vascular risk factors, and diabetes), cognitive frailty, biological factors, tolerance to cancer treatment, and psychological status may contribute to exacerbating cognitive difficulties. Aging may potentially impact inflammation, oxidative stress, cell senescence, and DNA damage and lead to a decrease in telomere length, which may cause cognitive deficits [17, 37–40]. Physiological factors such as the patient’s genetic makeup (e.g., the Apolipoprotein E (ApoE) associated with cognitive impairment related to Alzheimer’s disease, brain trauma, and aging [41]), hormone levels, the inflammatory response to cancer treatments, postoperative cognitive dysfunctions, fatigue, and sleep difficulty or hypersomnia could also affect cognition. The patient’s psychological status including degree of anxiety, depression, and stress increases vulnerability regarding cognitive function [42]. Lastly, it may be that other risk factors, such as low socioeconomic status, diet and nutrition, sedentary lifestyle, or alcohol and tobacco consumption, influence the development of both cancer and cognitive impairment [43]. However, the main cause of neuropsychological deficits in patients treated for cancer is chemotherapy [44].

Studies in elderly patients require a longitudinal design to assess cognition before any treatment insofar as these patients are more likely to exhibit age-related cognitive impairment before treatment compared to younger patients. Thus, future research should take into account the impact of chemotherapy and antiangiogenic treatment on cognition in order to better understand the trajectory of cognitive decline. Sufficient numbers of older patients and geriatric assessment of functional status should be included. Indeed, therapy-associated cognitive changes may affect an older patient’s ability to perform daily activities. Cognitive assessment should also include batteries of neuropsychological tests rather than screening tests and should target cognitive domains hypothesized to be impacted by treatment, such as memory, executive functions, attention, and information processing speed. Such assessment should not be too long owing to the potential impact of fatigue in elderly patients [33].