title: Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?
abstract: There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients.
authors: Departments of Oncology and Population Sciences, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC. Electronic address: mandelbj@georgetown.edu.
authors: Jeanne S
authors: JS
authors: Mandelblatt
authors: Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA.
authors: Arti
authors: A
authors: Hurria
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences and the Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors: Brenna C
authors: BC
authors: McDonald
authors: Center for Neuroimaging, Department of Radiology and Imaging Sciences and the Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN.
authors: Andrew J
authors: AJ
authors: Saykin
authors: Departments of Neurology and Neurosurgery and Director, Clinical Core, BU Alzheimer's Disease Center, Boston University School of Medicine, Boston, MA.
authors: Robert A
authors: RA
authors: Stern
authors: Department of Neurology, Georgetown University Medical Center, Georgetown University, Washington, DC.
authors: John W
authors: JW
authors: VanMeter
authors: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
authors: Meghan
authors: M
authors: McGuckin
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors: Tiffani
authors: T
authors: Traina
authors: Department of Medicine, Georgetown University; Virginia Cancer Specialists, US Oncology, Arlington, VA.
authors: Neelima
authors: N
authors: Denduluri
authors: Department of Neurology, Georgetown University Medical Center, Georgetown University, Washington, DC.
authors: Scott
authors: S
authors: Turner
authors: Department of Psychology, Georgetown University, Washington, DC.
authors: Darlene
authors: D
authors: Howard
authors: Division of Population Science, Moffitt Cancer Center, Tampa, FL.
authors: Paul B
authors: PB
authors: Jacobsen
authors: Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Psychiatry, Weill Cornell Medical College, New York, NY.
authors: Tim
authors: T
authors: Ahles
mesh_terms: D000368:Aged; D000375:Aging / Q000523:psychology*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications / Q000523:psychology* / Q000628:therapy; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D058245:Cognitive Reserve; D005260:Female; D016330:Frail Elderly / Q000523:psychology*; D015577:Geriatric Assessment; D006801:Humans
chemical_list: D000970:Antineoplastic Agents