Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?

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

Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?

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

Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity?

PURPOSE: To determine if older patients with breast cancer have cognitive impairment before systemic therapy. PATIENTS AND METHODS: Participants were patients with newly diagnosed nonmetastatic breast cancer and matched friend or community controls age > 60 years without prior systemic treatment, dementia, or neurologic disease. Participants completed surveys and a 55-minute battery of 17 neuropsychological tests. Biospecimens were obtained for APOE genotyping, and clinical data were abstracted. Neuropsychological test scores were standardized using control means and standard deviations (SDs) and grouped into five domain z scores. Cognitive impairment was defined as any domain z score two SDs below or ≥ two z scores 1.5 SDs below the control mean. Multivariable analyses evaluated pretreatment differences considering age, race, education, and site; comparisons between patient cases also controlled for surgery. RESULTS: The 164 patient cases and 182 controls had similar neuropsychological domain scores. However, among patient cases, those with stage II to III cancers had lower executive function compared with those with stage 0 to I disease, after adjustment (P = .05). The odds of impairment were significantly higher among older, nonwhite, less educated women and those with greater comorbidity, after adjustment. Patient case or control status, anxiety, depression, fatigue, and surgery were not associated with impairment. However, there was an interaction between comorbidity and patient case or control status; comorbidity was strongly associated with impairment among patient cases (adjusted odds ratio, 8.77; 95% CI, 2.06 to 37.4; P = .003) but not among controls (P = .97). Only diabetes and cardiovascular disease were associated with impairment among patient cases. CONCLUSION: There were no overall differences between patients with breast cancer and controls before systemic treatment, but there may be pretreatment cognitive impairment within subgroups of patient cases with greater tumor or comorbidity burden