Alzheimer disease–related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study

Author:

Mandelblatt Jeanne1ORCID,Dage Jeffrey L2,Zhou Xingtao3ORCID,Small Brent J4,Ahles Tim A5,Ahn Jaeil3ORCID,Artese Ashley6,Bethea Traci N7,Breen Elizabeth C89,Carroll Judith E89,Cohen Harvey J10,Extermann Martine11ORCID,Graham Deena12,Claudine Isaacs7,Jim Heather S L13,McDonald Brenna C14,Nakamura Zev M15,Patel Sunita K16,Rebeck G William17,Rentscher Kelly E18,Root James C5ORCID,Russ Kristen A19,Tometich Danielle B13,Turner R Scott20,Van Dyk Kathleen821ORCID,Zhai Wanting3,Huang Li-Wen22,Saykin Andrew J14

Affiliation:

1. Georgetown Lombardi Institute for Cancer and Aging Research, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC, USA

2. Stark Neurosciences Research Institute, Department of Neurology, Indiana University School of Medicine , Indianapolis, IN, USA

3. Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University , Washington, DC, USA

4. School of Aging Studies, University of South Florida, and Health Outcomes and Behavior Program, Moffitt Cancer Center , Tampa, FL, USA

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

6. Department of Exercise Science and Health Promotion, Charles E. Schmidt College of Science, Florida Atlantic University , Boca Raton, FL, USA

7. Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University , Washington, DC, USA

8. Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California , Los Angeles, Los Angeles, CA, USA

9. Cousins Center for Psychoneuroimmunology, University of California , Los Angeles, Los Angeles, CA, USA

10. Department of Medicine, Center for the Study of Aging and Human Development, Duke University Medical Center , Durham, NC, USA

11. Senior Adult Oncology Program, Department of Oncology, Moffitt Cancer Center, University of South Florida , Tampa, FL, USA

12. John Theurer Cancer Center, Hackensack University Medical Center , Hackensack, NJ, USA

13. Department of Health Outcomes and Behavior, Moffitt Cancer Center , Tampa, FL, USA

14. Department of Radiology and Imaging Sciences, Melvin and Bren Simon Comprehensive Cancer Center, and Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine , Indianapolis, IN, USA

15. Department of Psychiatry, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA

16. Department of Population Sciences and Department of Supportive Care Medicine, City of Hope Comprehensive Cancer Center , Duarte, CA, USA

17. Department of Neuroscience, Georgetown University , Washington, DC, USA

18. Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin Cancer Center, Medical College of Wisconsin , Milwaukee, WI, USA

19. Department of Medical and Molecular Genetics and National Centralized Repository for Alzheimer’s and Related Dementias, Indiana University School of Medicine , Indianapolis, IN, USA

20. Department of Neurology, Georgetown University , Washington, DC, USA

21. Jonsson Comprehensive Cancer Center, University of California, Los Angeles , Los Angeles, CA, USA

22. Division of Hematology/Oncology, University of California San Francisco and San Francisco Veterans Affairs Medical Center , San Francisco, CA, USA

Abstract

Abstract Purpose We evaluated whether plasma Alzheimer disease (AD)–related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors. Methods We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant. Results There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008). Conclusion The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.

Funder

National Institute on Aging

National Institutes of Health

National Cancer Institute

Georgetown Lombardi Comprehensive Cancer Center for support of the Biostatistics and Bioinformatics Resource

Non-Therapeutic Shared Resource

NIA

UCLA Cousins Center for Psychoneuroimmunology

NCRAD Biomarker Assay Lab

NCRAD

Indiana Biobank and the Indiana Clinical and Translational Sciences Institute

Publisher

Oxford University Press (OUP)

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