Individuals addicted to opioids have a 56% higher risk of developing dementia than non-users, according to a study led by researchers at Oxford Population Health and the Department of Psychiatry, University of Oxford. The findings are published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
Opioids are a class of natural, semi-synthetic, and synthetic drugs that include prescription pain medications such as oxycodone and fentanyl, and illegal drugs such as heroin. They work by binding to opioid receptors in the brain and spinal cord, blocking pain signals and producing feelings of euphoria.
Over-prescribing of opioids in the 1990s, particularly in the United States and Canada, contributed to a wave of opioid misuse and overdose deaths that led the US Department of Health and Human Services to declare a public health emergency in 2017. More recently, the opioid crisis has been driven by illegally manufactured fentanyl.
Assessing long-term effects on brain health
While the short-term effects of opioid use disorder (OUD) are well known, there is an urgent need to better understand their long-term effects on brain health as millions of people struggling with opioid addiction age.
Drawing conclusions from emerging evidence has been complicated by the difficulty of distinguishing the effects of opioid addiction from other factors that may contribute to dementia, such as psychiatric disorders, chronic pain or alcohol abuse. To address these difficulties, the researchers used multiple methods to investigate how brain health is impacted by opioid use disorder (a condition involving compulsive use of opioids, which can develop from dependence on prescription or illicit drugs).
Firstly, they analysed over 220,000 health records from the US Million Veteran Program (MVP) – a database of DNA and health records from more than a million retired US military service members.
They then compared the MVP data to data from several other large studies, including the UK Biobank. Finally, they used genetic analysis to disentangle opioid use from other potential causes of dementia.
Direct link between opioid use and dementia risk
Among the MVP participants, 9,399 had a diagnosis of OUD. Their average age at enrolment was 58, 91% were male, 78% were of European ancestry, 11% were from African ancestry, and they were more likely to be smokers, heavy drinkers and users of cannabis than those without OUD.
During up to nine years of follow-up, 8,397 of all participants developed dementia, with those diagnosed with opioid use disorder 56% more likely to develop dementia than others. The findings also revealed a strong association between OUD and incidence of Alzheimer’s disease and vascular dementia among the participants with European ancestry.
The genetic analysis revealed that the effects on the brain were likely to be driven by the impact of opioid exposure rather than any inherited tendency towards opioid addiction.
Senior Clinical Researcher at Oxford Population Health and lead author of the study, Dr Anya Topiwala said ‘While the short-term effects of opioids are well known, our findings show that opioid use disorder may also have important long-term consequences for brain health, including a higher risk of dementia. Using large-scale data and genetic methods, we found evidence suggesting this link may be causal, pointing to the direct impact of opioid exposure rather than underlying genetic risk.’
The mechanisms linking opioid addiction to dementia remain unclear, but the study authors speculate that long-term opioid abuse may contribute to hardening and narrowing of the arteries (atherosclerosis), infection and hypotension, all of which can reduce the flow of blood and oxygen to the brain.
They also noted that dementia may have gone undiagnosed in some opioid users where the effects of their addiction obscured the symptoms of cognitive decline.
‘This work underscores the need for medicine safety, preventive strategies, and further investigation into the neurological consequences of chronic opioid exposure,’ said Topiwala.