Supraphysiologic-dose anabolic–androgenic steroid use: A risk factor for dementia?

Abstract

Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.

Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review

“…Recent evidence, by administrating neuropsychological tests to weightlifters both AAS users and nonusers, demonstrated a cognitive disfunction due to long-term high AAS exposure [ 46 ]. In this regard, oxidative stress and apoptosis due to AASs abuse may lead to neurodegeneration and dementia, especially in long-term users, adolescents and young adults [ 47 , 48 ].…”

Aggression and Psychological Distress in Male and Female Anabolic-Androgenic Steroid Users: A Multigroup Latent Class Analysis

“…Despite experiencing aesthetic and performance benefits (2, 3), users often report adverse physiological and psychological effects (4)(5)(6)(7)(8), such as lack of impulse control, hostility, and high levels of aggressive and violent behaviors (9)(10)(11). Indeed, a recent meta-analysis of 12 randomized controlled trials has shown that among healthy males, AAS administration increases self-reported aggression (12).…”

Long-term anabolic androgenic steroid use is associated with deviant brain aging

“…Accumulating evidence suggests that prolonged AAS use has adverse effects on the brain (12, 36, 37, 39, 42, 43). Using brain scans and brain age prediction based on an independent training set we found evidence of higher relative global, frontal, temporal, occipital and insular brain age in 130 male AAS users compared to 99 male WLC.…”

“…Also, compared to non-using weightlifters, AAS-exposed weightlifters have shown to perform poorer on tests assessing working memory (12, 39, 40), executive functions (12, 40, 41), learning and memory (12, 39, 41), processing speed and problem solving (12, 40). Although correlational, such findings have led to the hypothesis that high-dose AAS users are at risk for accelerated brain aging (42, 43).…”