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Risk of dementia following androgen deprivation therapy for treatment of prostate cancer

Prostate Cancer and Prostatic Diseases volume 23, pages 410–418 (2020)Cite this article

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Abstract

Background

Evidence for androgen deprivation therapy (ADT) and risk of dementia is both limited and mixed. We aimed to assess the association between ADT and risk of dementia among men with localized and locally advanced prostate cancer (PCa).

Methods

We conducted a retrospective cohort study using SEER-Medicare-linked data among 100,414 men aged ≥ 66 years and diagnosed with localized and locally advanced PCa (cT1–cT4) between 1992 and 2009. We excluded men with a history of stroke, dementia, or use of psychiatric services. Men were followed until death or administrative end of follow-up at 36 months. Inverse-probability weighted Fine-Gray models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for Alzheimer’s, all-cause dementia, and use of psychiatric services by duration of pharmacologic ADT (0, 1–6, and ≥ 7 months).

Results

Among 100,414 men with PCa (median age 73 [IQR: 69–77] years; 84% white, 10% black), 38% (n = 37,911) received ADT within 6 months of diagnosis. Receipt of any pharmacologic ADT was associated with a 17% higher risk of all-cause dementia (HR 1.17, 95% CI 1.07–1.27), 23% higher risk of Alzheimer’s (HR 1.23, 95% CI 1.11–1.37), and 10% higher risk of psychiatric services use, though the confidence interval included the null (HR 1.10, 95% CI 1.00–1.22). Longer duration of ADT (≥7 months) was associated with a 25% higher risk of all-cause dementia, 34% higher risk of Alzheimer’s, and 9% higher risk of psychiatric services, compared with no ADT.

Conclusions

Our study supports an association between pharmacologic ADT and higher risk of all-cause dementia, Alzheimer’s, and use of psychiatric services among men with localized and locally advanced PCa.

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Authors and Affiliations

  1. Center for Surgery and Public Health, Division of Urological Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Anna Krasnova, Maya Marchese, Alexander P. Cole, Stuart R. Lipsitz, Adam S. Kibel & Quoc-Dien Trinh

  2. Mailman School of Public Health, Columbia University, New York, NY, USA

    Anna Krasnova

  3. SUNY Downstate Medical Center, New York, NY, USA

    Matthew Epstein

  4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Barbra A. Dickerman & Lorelei A. Mucci

  5. Harvard Medical School, Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    Paul L. Nguyen

  6. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Toni K. Choueiri & Maxine Sun

  7. Research Program in Men’s Health, Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Shehzad Basaria

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Correspondence to Quoc-Dien Trinh.

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Conflict of interest

Toni K. Choueiri reports institutional and personal research support from AstraZeneca, Alexion, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda. Toni K. Choueiri reports honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc (Healthcare Communications Company with several brands such as OnClive, PeerView and PER), L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, NEJM, Lancet Oncology, Heron Therapeutics, Lilly. Toni K. Choueiri reports consulting or advisory role with AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Heron Therapeutics, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Lilly, Ipsen, Up-to-Date, NCCN, Analysis Group. Toni K. Choueiri reports no speaker’s bureau, no leadership or employment in for-profit companies. Other present or past leadership roles of Toni K. Choueiri: Director of GU Oncology Division at Dana-Farber and past President of medical Staff at Dana-Farber, member of NCCN Kidney panel and the GU Steering Committee, past chairman of the Kidney Cancer Association Medical and Scientific Steering Committee. Additionally, Toni K. Choueiri reports no patents, royalties or other intellectual properties. He reports travel, accommodations, expenses, in relation to consulting, advisory roles, or honoraria. His medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies. Furthermore, the institution (Dana-Farber Cancer Institute) may have received additional independent funding of drug companies or/and royalties potentially involved in research around the subject matter. Adam S. Kibel reports honoraria from profound, InSightec, Janssen, Merck, Pfizer, Blue Earth Diagnostics. Quoc-Dien Trinh is supported by the Brigham Research Institute Fund to Sustain Research Excellence, the Bruce A. Beal and Robert L. Beal Surgical Fellowship, the Genentech Bio-Oncology Career Development Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology, a Health Services Research pilot test grant from the Defense Health Agency, the Clay Hamlin Young Investigator Award from the Prostate Cancer Foundation and an unrestricted educational grant from the Vattikuti Urology Institute. All remaining authors declare no conflicts of interest.

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Krasnova, A., Epstein, M., Marchese, M. et al. Risk of dementia following androgen deprivation therapy for treatment of prostate cancer. Prostate Cancer Prostatic Dis 23, 410–418 (2020). https://doi.org/10.1038/s41391-019-0189-3

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