Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Molecular mechanisms underlying the effects of regular exercise on substance use disorder-associated cognitive impairment and dementia risk: A narrative review

Articles in Press

Document Type : Review Article

Authors
Forough Radfar 1
Fatemeh Tirgar 2
Monireh Jahani 3
Maryam Farahmandfar 3
1 Department of Sports Behavioral and Cognitive Sciences, Sports and Health Sciences College, Tehran University, Tehran, Iran
2 Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran
3 Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
10.22038/ijbms.2026.96470.20790
Abstract
Dementia is one of the most widespread neurodegenerative conditions worldwide and is accompanied by cell death in the central nervous system (CNS). Risk factors include age, genetics, CNS trauma, cardiovascular disease, environmental factors, and stressors. Stress, especially oxidative stress, disrupts mitochondrial respiration, causing mitochondrial damage in neurodegenerative illnesses like dementia. The role of oxidative stress in dementia progression has been studied recently. As a progressive disorder, addiction may be a stressor that induces oxidative stress. The psychological and psychophysiological effects of addiction can exacerbate oxidative stress, neuronal death, and dementia progression. Identifying an effective alternative therapy to prevent oxidative stress-induced dementia development could be advantageous. Exercise reverses dementia progression by lowering oxidative stress-related neuropathological alterations in addiction. Regular exercise can help overcome addiction’s cognitive effects in a complementary, affordable, and accessible way.
This review will discuss dementia progression and oxidative stress-induced dysfunction. We will also examine addiction as an oxidative stressor in this neurodegenerative illness. To this end, we searched PubMed and Google Scholar for articles published between 2015 and 2025 using the keywords dementia, cognitive impairment, exercise, physical activity, addiction, METH, and oxidative stress. Finally, the last part of the review provides information to improve the current understanding of the role of regular exercise in the progression of substance use disorder-associated cognitive impairment and dementia risk.
Keywords
Cognitive impairment
Cognitive rehabilitation
Exogenous stressors
Noninflammatory
Physical activity intervention
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 10 November 2026