Cognitive Effects of Cancer and Its Treatments at the Intersection of Aging: What Do We Know; What Do We Need to Know?
Section snippets
Aging, Frailty, and Cognitive Decline
Aging is the net effect of the temporal accumulation of damage to cellular processes and systems, loss of compensatory mechanisms, and increased vulnerability to disease and death. Closely aligned to this definition is the clinical concept of frailty, which can be considered a phenotype of aging. This phenotype is characterized by a diminished biologic reserve and resistance to stressors caused by collective declines across physiologic systems, leading to vulnerability to insult and adverse
Models of aging
The constellation of intersecting factors related to cancer-related cognitive decline, frailty, and aging raises several provocative questions: If cancer therapy impacts cognitive function, does the trajectory of dysfunction parallel that of normal aging (phase shift hypothesis), or is the trajectory of dysfunction accelerated in comparison to normal aging (accelerated aging hypothesis)?5 Is the lowest common denominator a depletion of reserve leading to a frail phenotype (reliability theory of
Measurement Issues
There are many methodological considerations in studying the complex interactions between cancer, cancer therapy and cognitive function. In this section we highlight several concerns specific to evaluations of the role of aging and needs of older patients. For excellent reviews of international consensus panels on methods for studying cancer and cognition the reader is referred to summaries of the International Cognition and Cancer Task Force.35, 142, 151
First, this is a field that will require
Practice Implications
From the preceding review it is apparent that there is a fairly strong body of evidence linking aging processes to cancer-related cognitive declines. But it is also clear that there are many unanswered questions. While the research community grapples with how to provide rigorous empiric evidence for older cancer patients, clinicians are faced every day with caring for the growing number of older cancer patients presenting to their practices. What then are the implications of what we think we
Conclusions
There is a strong albeit non-universal body of literature supporting the phenomenon of cognitive decline after breast cancer and its systemic therapies. This side effect is likely to be only experienced by a sub-group of patients, and while risk factors have been identified, biological mechanisms and pathways have not been fully elucidated. From what we do know, it appears that there are common underlying processes at the intersection of cancer, aging and the frail phenotype. Geriatric
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This research was supported by the National Cancer Institute (NCI) at the National Institutes of Health (NIH) grant no. R01CA129769; in part by NCI, NIH grants no. U10 CA 84131, R01CA 127617, and K05CA096940 to J.S.M.; and by NCI, NIH grant no. P30CA51008 to Lombardi Comprehensive Cancer Center (synergy developmental funds to J.S.M. and J.V.M.). The work of A.J.S. and B.C.M. was supported in part by R01 CA101318, P30 CA082709, R25 CA117865, U54 RR025761, C06 RR020128, S10 RR027710, R01 AG019771, P30 AG010133, F30 AG039959, and U24AG021886. The work of R.A.S. was supported by NIH grant no. P30-AG13846 to Boston University Alzheimer’s Disease Center. The work of A.H. was supported in part by NIH grant no. U54 132378 and by the Starr Foundation.
Financial disclosures: Hurria: Seattle Genetics, Amgen Pharmaceuticals, and Genetech (consultation); Glaxo Smith Kline, Abraxis Bioscience, and Celgene (research support). All remaining authors have declared no conflicts of interest.