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.

Keywords: Aging; Alcohol; Alzheimer's disease; Amyloid; Anabolic-androgenic steroid; ApoE; Aquaporin 4; Body-building; Boldenone; Cannabis; Cocaine; Dementia; Estrogen; GSK3β; Heroin; Homocysteine; Hypogonadism; Insomnia; Insulin Degrading enzyme; Low-density lipoprotein receptor-related protein1; Magnetic resonance imaging; Magnetic resonance spectroscopy; Menopause; Methamphetamine; Mild Cognitive Impairment; Morphine; Muscularity; N-acetylcysteine; Nandrolone; Neprilysin; Neurodegeneration; Nrf2; Opioid; Oxidative stress; Oxymetholone; PET imaging; Performance-enhancing drugs; Polydrug use; Prealbumin; Presenilin; Protein phosphatase 2A; Scyllo-inositol; Sex-steroid; Sleep disturbances; Stanozolol; Substance use disorder; Testosterone; Tobacco; Zinc; tau; α-secretase; β-secretase; γ-secretase.