Statins protect against dementia in diabetic prostate cancer patients on ADT
Statins appear to exert neuroprotective effects in diabetic prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT), with a recent study showing that the drug confers benefit for the risk of dementia. The benefit is greater with higher statin adherence and intensity.
PCa patients treated with higher doses and longer durations of ADT are at high risk of dementia, possibly due to persistently low levels of testosterone, according to the investigators.
“In this study, we demonstrated a protective effect of statins against dementia in patients receiving ADT. [However], statin use failed to protect against dementia … when the annual equivalent dose of GnRH agonists [was] >45 mg,” they added.
Therefore, the investigators suggest limiting the annual equivalent dose of GnRH agonists to ≤45 mg to reap a better dementia-prevention effect from statin use.
The study included a propensity-matched cohort of 1,006 statin users and 1,006 nonusers with a mean follow up of 3.5 years. These participants had type 2 diabetes mellitus (T2DM) and PCa, for which they received ADT. Overall, there were 179 patients diagnosed with dementia: 84 (8.4 percent) were statin users and 95 (9.4 percent) were statin-naïve.
Compared with nonuse, statin use was associated with a decreased risk of developing dementia (hazard ratio [HR], 0.70, 95 percent CI, 0.52–0.94). A significant risk decrease was observed with increasing duration of use (event rates: 9.2 percent for nonusers, 8.6 percent for ≤180 days users and 7.5 percent for >180 days users; p-trend=0.002) and with use of lipophilic vs hydrophilic statins (event rates, 6.5 percent vs 10.3 percent; HR, 0.54, 0.34–0.86; p=0.009). [Prostate Cancer Prostatic Dis 2019;22:276-283]
“To the best of our knowledge, this is the first large-scale cohort study to investigate the association between the use of statin and the risk of subsequent dementia in T2DM patients with PCa receiving ADT,” the investigators said.
They pointed out that statins decrease low-density lipoprotein cholesterol levels while reducing cerebral arterial atherosclerosis and inflammatory process, which have beneficial effects in terms of dementia risk. [Arch Neurol 2004;61:705-714; J Intern Med 2015;277:343-352]
“Statins also decrease oxidative stress via the inhibition of NADPH oxidase and reduce β-amyloid production in the central nervous system, which improves cognition,” they added.
The study had several limitations, including the lack of data on the prostate-specific antigen levels, clinical stages of PCa and Gleason scores, the limited external generalizability, and the relatively short follow-up duration.
“Further studies are warranted to obtain a better understanding of the protective effect of statins against dementia among patients receiving ADT,” the investigators said.