Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors

Tim A Ahles; Elizabeth Schofield; Yuelin Li; Elizabeth Ryan; Irene Orlow; Sunita K Patel; Tiffany Traina; James C Root

doi:10.1007/s11764-023-01365-6

Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors

J Cancer Surviv. 2023 Mar 24. doi: 10.1007/s11764-023-01365-6. Online ahead of print.

Authors

Tim A Ahles¹, Elizabeth Schofield², Yuelin Li², Elizabeth Ryan², Irene Orlow³, Sunita K Patel⁴, Tiffany Traina⁵, James C Root²

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ahlest@mskcc.org.
² Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³ Department of Epidemiology and Biostatistics, Molecular Epidemiology Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ Departments of Population Science and Supportive Care Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
⁵ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

PMID: 36964293
DOI: 10.1007/s11764-023-01365-6

Abstract

Purpose: This study aims to examine whether cognitive function in older, long-term breast cancer survivors is both a direct effect of cancer and cancer treatments and an indirect effect mediated by deficit accumulation.

Patients and methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 220) and age- and education-matched non-cancer controls (N = 123) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological tests and the comprehensive geriatric assessment which was used to calculate the deficit accumulation frailty index (DAFI). Blood or saliva samples for APOE genotyping were collected at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or and 50% were not exposed to chemotherapy.

Results: Latent variable mediation analysis revealed that cognitive performance was mediated by deficit accumulation for all three domains. The direct effect of cancer diagnosis and treatment history was significant for the Language domain (p = 0.04), a trend for the learning and memory domain (p = 0.054), and non-significant for the attention, processing speed, executive function (APE) domain. Carrying the APOE ε4 allele had a significant negative direct effect on the APE domain (p = 0.05) but no indirect effect through deficit accumulation.

Conclusion: Cognitive function in older, long-term breast cancer survivors appears to be primarily mediated through deficit accumulation.

Implications for cancer survivors: These findings have important clinical implications suggesting that the most effective intervention to prevent or slow cognitive aging in older cancer survivors may be through prevention or management of comorbidities and interventions that maintain functional capacity (exercise, physical therapy) and social and mental health.

Keywords: Breast cancer; Cognition; Deficit accumulation.

Abstract

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