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

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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.

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Data availability

Data can be requested by contacting the corresponding author.

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Funding

This research was supported by grants from the National Cancer Institute (TA: R01 CA172119, U54 CA137788, P30 CA008748), the American Cancer Society (SKP: RSG-17–023-01-CPPB), and Internal MSK grants (IO: Society of MSK, Brain Tumor Center Award).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Tim A. Ahles, Elizabeth Schofield, Yuelin Li, Elizabeth Ryan & James C. Root

  2. Department of Epidemiology and Biostatistics, Molecular Epidemiology Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Irene Orlow

  3. Departments of Population Science and Supportive Care Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    Sunita K. Patel

  4. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Tiffany Traina

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  1. Tim A. Ahles
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Contributions

TAA, ES, and YL wrote the main manuscript. ES prepared the figures and tables. All authors reviewed and edited the manuscript.

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Correspondence to Tim A. Ahles.

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Ahles, T.A., Schofield, E., Li, Y. et al. Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors. J Cancer Surviv (2023). https://doi.org/10.1007/s11764-023-01365-6

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