Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Statin reduces the risk of dementia in diabetic patients receiving androgen deprivation therapy for prostate cancer




Androgen deprivation therapy (ADT) has been reported to increase the risk of dementia. Statin use decreases the risk of dementia. This study is aimed to investigate the association of statin use and dementia in type 2 diabetic (T2DM) patients receiving ADT.


Using the National Health Insurance Research Database of Taiwan, we conducted a population-based nationwide cohort study of T2DM patients newly diagnosed with prostate cancer (PCa) between 1998 and 2013. To test statin effects on dementia in T2DM patients receiving ADT, cox proportional hazards models with 1:1 propensity score-matched analysis were used. We divided the study subjects into a statin group and a statin-naive group. The primary outcome was dementia.


Of the 9855 selected T2DM patients newly diagnosed with PCa between 1998 and 2013, 5427 patients received ADT for their PCa. After propensity score matching, 1006 statin users and 1006 non-statin users were included in the study cohort, with a mean follow-up period of 3.5 years for the statin group. Among those patients, 179 (8.7%) were newly diagnosed with dementia. A propensity score-matched analysis (hazard ratio = 0.70, 95% confidence interval = 0.52–0.94) demonstrated a significantly decreased risk of subsequent dementia in the statin users with an absolute risk reduction by 1%. A significant decrease in the risk of dementia with increasing statin duration was also demonstrated (P for trend = 0.002).


Statin use in T2DM patients receiving ADT for PCa had decreased risk of dementia, with statin adherence and intensity augmenting this benefit.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3


  1. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22:232–40.

    CAS  Article  Google Scholar 

  2. Parker C, Gillessen S, Heidenreich A, Horwich A; ESMO Guidelines Committee, Cervantes A, et al. Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v69–77.

    Article  Google Scholar 

  3. Levine GN, D'Amico AV, Berger P, Clark PE, Eckel RH, Keating NL, et al. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. CA: Cancer J. Clin. 2010;60:194–201.

    Article  Google Scholar 

  4. Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009;115:2388–99.

    Article  Google Scholar 

  5. Vest RS, Pike CJ. Gender, sex steroid hormones, and Alzheimer’s disease. Horm Behav. 2013;63:301–7.

    CAS  Article  Google Scholar 

  6. Rosario ER, Chang L, Stanczyk FZ, Pike CJ. Age-related testosterone depletion and the development of Alzheimer disease. JAMA. 2004;292:1431–2.

    CAS  Article  Google Scholar 

  7. Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER, et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005;64:2063–8.

    CAS  Article  Google Scholar 

  8. Nead KT, Gaskin G, Chester C, Swisher-McClure S, Leeper NJ, Shah NH. Association between androgen deprivation therapy and risk of dementia. JAMA Oncol. 2017;3:49–55.

    Article  Google Scholar 

  9. Nead KT, Sinha S, Nguyen PL. Androgen deprivation therapy for prostate cancer and dementia risk: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017;20:259–64.

    CAS  Article  Google Scholar 

  10. Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75:1195–1202.

    CAS  Article  Google Scholar 

  11. Reitz C, Tang MX, Luchsinger J, Mayeux R. Relation of plasma lipids to Alzheimer disease and vascular dementia. Arch Neurol. 2004;61:705–14.

    Article  Google Scholar 

  12. Wu CK, Yang YH, Lin TT, Tsai CT, Hwang JJ, Lin JL, et al. Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis. J Intern Med. 2015;277:343–52.

    CAS  Article  Google Scholar 

  13. Liu JM, Lin PH, Hsu RJ, Chang YH, Cheng KC, Pang ST, et al. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer. Medicine (Baltimore). 2016;95:e4475.

    Article  Google Scholar 

  14. Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, et al. Association between nucleoside analogues and risk of hepatitis B virus–related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012;308:1906–14.

    CAS  Article  Google Scholar 

  15. Chen PY, Liu SK, Chen CL, Wu CS. Long-term statin use and dementia risk in Taiwan. J Geriatr Psychiatry Neurol. 2014;27:165–71.

    Article  Google Scholar 

  16. Austin PC. Statistical criteria for selecting the optimal number of untreated subjects matched to each treated subject when using many-to-one matching on the propensity score. Am J Epidemiol. 2010;172:1092–7.

    Article  Google Scholar 

  17. Park HS, Schoenfeld JD, Mailhot RB, Shive M, Hartman RI, Ogembo R, et al. Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis. Ann Oncol. 2013;24:1427-34.

    CAS  Article  Google Scholar 

  18. Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nat Rev Urol. 2017;14:107–19.

    CAS  Article  Google Scholar 

  19. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367:1792–802.

    CAS  Article  Google Scholar 

  20. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.

    CAS  Article  Google Scholar 

  21. Erdös B, Snipes JA, Tulbert CD, Katakam P, Miller AW, Busija DW. Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production. Am J Physiol Heart Circ Physiol. 2006;290:H1264–70.

    Article  Google Scholar 

  22. Handattu SP, Garber DW, Monroe CE, van Groen T, Kadish I, Nayyar G, et al. Oral apolipoprotein A–I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2009;34:525–34.

    CAS  Article  Google Scholar 

  23. Carlsson CM, Nondahl DM, Klein BE, McBride PE, Sager MA, Schubert CR, et al. Increased atherogenic lipoproteins are associated with cognitive impairment: effects of statins and subclinical atherosclerosis. Alzheimer Dis Assoc Disord. 2009;23:11–7.

    CAS  Article  Google Scholar 

  24. Wang Q, Yan J, Chen X, Li J, Yang Y, Weng J, et al. Statins: multiple neuroprotective mechanisms in neurodegenerative diseases. Exp Neurol. 2011;230:27–34.

    CAS  Article  Google Scholar 

  25. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007;297:177–86.

    CAS  Article  Google Scholar 

  26. Flint AC, Conell C, Ren X, Kamel H, Chan SL, Rao VA, et al. Statin adherence is associated with reduced recurrent stroke risk in patients with or without atrial fibrillation. Stroke. 2017;48:1788–94.

    CAS  Article  Google Scholar 

  27. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356:1627–31.

    CAS  Article  Google Scholar 

  28. Cramer C, Haan MN, Galea S, Langa KM, Kalbfleisch JD. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology. 2008;71:344–50.

    CAS  Article  Google Scholar 

  29. Chen JM, Chang CW, Chang TH, Hsu CC, Horng JT, Sheu WH. Effects of statins on incident dementia in patients with type 2 DM: a population-based retrospective cohort study in Taiwan. PLoS ONE. 2014;9:e88434.

    Article  Google Scholar 

  30. Ott BR, Daiello LA, Dahabreh IJ, Springate BA, Bixby K, Murali M, et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials. J Gen Intern Med. 2015;30:348–58.

    Article  Google Scholar 

  31. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23:871–80.

    Article  Google Scholar 

  32. Evans MA, Golomb BA. Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy. 2009;29:800–11.

    CAS  Article  Google Scholar 

  33. U.S. Food and Drug Administration. FDA Consumer Health Information: FDA Expands Advice on Statin Risks. 2012.

  34. Engelberg H. Low serum cholesterol and suicide. Lancet. 1992;339:727–9.

    CAS  Article  Google Scholar 

  35. Hammond J, Le Q, Goodyer C, Gelfand M, Trifiro M, LeBlanc A. Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. J Neurochem. 2001;77:1319–26.

    CAS  Article  Google Scholar 

Download references


This study was supported by the Ministry of Science and Technology Taiwan (Grants No. MOST 104-2320-B-016-012-MY3), the Taoyuan General Hospital, Ministry of Health and Welfare (Grants No. PYT10702), and the Chang Gung Memorial Hospital, Taiwan (grant CGRPG2F0011, CLRPG2C0021, CLRPG2C0022, CLRPG2C0023, CLRPG2C0024, CLRPG2G0081)

Author information

Authors and Affiliations


Corresponding author

Correspondence to Ren-Jun Hsu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, JM., Chen, TH., Chuang, HC. et al. Statin reduces the risk of dementia in diabetic patients receiving androgen deprivation therapy for prostate cancer. Prostate Cancer Prostatic Dis 22, 276–283 (2019).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links