The intersection of cancer and aging: implications for physical activity and cardiorespiratory fitness effects on cognition

Abstract

Increasing 5-year survival rates of 69% in all cancer sites have led to over 15.5 million cancer survivors currently living in the United States [1]. Over 60% of cancer survivors are aged 65 years or older, and it is expected that older adults will comprise 70% of cancer diagnoses by 2030 [2]. Although living longer following a cancer diagnosis and treatment may appear to be a positive outcome, many cancer survivors will experience cognitive impairment which can be prevalent during active cancer therapy, remain elevated posttreatment, and impact quality of life (QoL) [3]. Cancer-related cognitive impairment (CRCI) parallels normal aging and may accelerate declines in aspects of physical condition that have established relationships with cognitive function [4]. This intersection of cancer and aging highlights the importance of studying long-term effects of cancer treatment, particularly cognitive impairment and brain health [4]. The majority of empirical research on CRCI has been in breast cancer survivors (BCS) and it is estimated that ~75% of all BCS report CRCI following treatment and the clinical prevalence of this impairment ranges from 17% to 75% [5]. Cognitive processes thought to be impaired include memory, learning, concentration, reasoning, executive function, attention, processing speed, and visual-spatial skills [5,6]. Importantly, these changes may occur both before and after treatment and have been reported up to 20 years posttreatment [5]. Evidence suggests changes in brain structure and function, hormonal changes, and neural degradation are similar among cancer patients posttreatment and healthy aging individuals [7–9]. However, the trajectory of cognitive decline after cancer treatment may occur earlier and at an accelerated rate in cancer survivors when compared with age-matched healthy adults. Given these parallel biological pathways, aging models may provide a useful platform for treating CRCI. There is strong and consistent evidence that aerobic physical activity (PA) and cardiorespiratory fitness (CRF) mitigate age-related neural degeneration and cognitive dysfunction and improve QoL in older adults [10,11]. While the physical and psychological health benefits of PA and CRF are well documented in cancer patients and survivors, the influences of PA and CRF on cognition and brain health have received limited attention in the oncology literature [12,13]. PA is increasingly being recommended as a promising behavioral approach to improve CRF and ameliorate cognitive dysfunction in cancer survivors [5,14]; however, preclinical and clinical studies are scarce [15]. Unfortunately, PA levels generally decrease after cancer diagnosis and rarely return to precancer levels after treatment ends [16,17]. One of the most important moderators of CRCI in cancer survivors may be CRF, which declines dramatically due to accelerated aging [18]. CRF has been associated with the preservation of cognitive function in older adults and increasing CRF mitigates age-related effects on brain structure and cognitive function [10,19]. Jones et al. [18] provide compelling data to suggest the effects of normal aging on CRF in BCS are exacerbated by cancer therapies such that fitness levels in BCS were 27% below ageand sex-predicted values. CRF values were significantly lower in the metastatic and adjuvant therapy groups relative to the post-therapy group. Additionally, their data suggested that a 40-year-old BCS had similar CRF levels to a 70-year-old healthy, sedentary woman. If CRF is associated with cognitive declines and brain structure independent of normal aging, then PA training interventions represent a lifestyle mechanism for the enhancement of CRF and remediation of CRCI and degradations to brain structure. There are few exercise training studies that have rigorously evaluated CRCI as a primary outcome in cancer survivors and few oncology studies that have tested PA as a treatment for CRCI. There is clearly a need to bridge this gap, as CRCI is an apparent consequence of cancer diagnosis and treatment, and non-pharmacologic treatments like PA have the potential to impact a host of other cancer-related sequelae also affecting QoL. Given the clinical importance of this research and growing body of research targeting PA, CRF, and CRCI, we recommend several areas of future research. The goal of these recommendations is to improve the development of research designs and measurement selection, and to establish homogeneity of CRCI-related studies across cancer survivor groups.