Cognitive effects of cancer and its treatments at the intersection of aging

What do we know; What do we need to know?

Jeanne S. Mandelblatt, Arti Hurria, Brenna McDonald, Andrew Saykin, Robert A. Stern, John W. Vanmeter, Meghan McGuckin, Tiffani Traina, Neelima Denduluri, Scott Turner, Darlene Howard, Paul B. Jacobsen, Tim Ahles

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)709-725
Number of pages17
JournalSeminars in Oncology
Volume40
Issue number6
DOIs
StatePublished - Dec 2013

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Neoplasms
Genetic Predisposition to Disease
Therapeutics
Cognitive Reserve
Research
Geriatric Assessment
Phenotype
Cell Aging
Telomere
Blood-Brain Barrier
Neuroimaging
DNA Repair
Cognition
Population
DNA Damage
Life Style
Alzheimer Disease
Oxidative Stress
Animal Models
Cognitive Dysfunction

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Cognitive effects of cancer and its treatments at the intersection of aging : What do we know; What do we need to know? / Mandelblatt, Jeanne S.; Hurria, Arti; McDonald, Brenna; Saykin, Andrew; Stern, Robert A.; Vanmeter, John W.; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B.; Ahles, Tim.

In: Seminars in Oncology, Vol. 40, No. 6, 12.2013, p. 709-725.

Research output: Contribution to journalArticle

Mandelblatt, JS, Hurria, A, McDonald, B, Saykin, A, Stern, RA, Vanmeter, JW, McGuckin, M, Traina, T, Denduluri, N, Turner, S, Howard, D, Jacobsen, PB & Ahles, T 2013, 'Cognitive effects of cancer and its treatments at the intersection of aging: What do we know; What do we need to know?', Seminars in Oncology, vol. 40, no. 6, pp. 709-725. https://doi.org/10.1053/j.seminoncol.2013.09.006
Mandelblatt, Jeanne S. ; Hurria, Arti ; McDonald, Brenna ; Saykin, Andrew ; Stern, Robert A. ; Vanmeter, John W. ; McGuckin, Meghan ; Traina, Tiffani ; Denduluri, Neelima ; Turner, Scott ; Howard, Darlene ; Jacobsen, Paul B. ; Ahles, Tim. / Cognitive effects of cancer and its treatments at the intersection of aging : What do we know; What do we need to know?. In: Seminars in Oncology. 2013 ; Vol. 40, No. 6. pp. 709-725.
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