Nonfatal opioid overdoses tend to be overlooked amid a crisis that killed more than 100,000 Americans last year. But people who survive overdoses are still at risk for health complications, including neurodegenerative issues, a new review from Drexel University researchers has found.

The study reviews available research on nonfatal opioid overdoses and how they might be linked to cognitive issues and, in some cases, Alzheimer’s disease-like changes in the brain. And it shows how people who have suffered an overdose need more care than a dose of naloxone, the overdose-reversing drug, researchers said.

“We save a person from [fatal] overdose, and this is kind of a checkmark,” said Janna Ataiants, one of the study’s authors and a senior research scientist at the department of community health and prevention in Drexel’s Dornsife School of Public Health. “This person is very vulnerable to long-term health consequences. But we think our job is done. It’s not done.”

Ataiants first became interested in the cognitive impacts of overdoses while conducting a research study on overdose risk with the Kensington public health organization Prevention Point, focusing primarily on women. In talks with study participants, she asked women if they’d experienced neurological symptoms. Many said they had memory issues, found themselves unable to concentrate or plan ahead, or were even displaying some motor dysfunctions like tremors.

“I did an analysis, and there was some correlation between the number of overdoses in their lifetime and these symptoms,” Ataiants said. That led her to pursue a wider review of the available research on the topic.

“Every time you experience an overdose, you may experience hypoxia -- ending the supply of oxygen to your brain. That’s the most adverse consequence. When you experience hypoxic injury, some of your neurons die, and some are injured,” Ataiants said.

It’s unclear whether a single nonfatal overdose, a single severe overdose, or repeated hypoxia from multiple overdoses initiates changes in the brain, the researchers wrote.

For people who suffer no more than a few overdoses, hypoxia may not have a lasting effect: the brain can develop new neural networks to compensate, Ataiants said. But repeated overdoses may have long-lasting effects. The review cites studies of the brains of opioid overdose victims that showed neurological changes similar to those seen in Alzheimer’s patients.

Overdoses can also lead to executive function issues, the researchers found, that make it difficult for someone to judge the dose of heroin they’re taking, or otherwise understand the risk of what they’re doing. It’s a cycle that itself can lead to another overdose, Ataiants said

The findings are especially alarming given the increasing contamination of Philadelphia’s -- and the country’s -- drug supply. Fentanyl, the powerful synthetic opioid that has replaced most of the city’s heroin, is behind most of Philadelphia’s fatal overdoses.

“I’m totally for a safe drug supply and for overdose prevention sites -- it’s better to have a safe supply in terms of neurocognitive health,” Ataiants said. If people using drugs understand the contents of what they’re about to inject or ingest, they’re less likely to overdose, and less likely to suffer the cognitive issues the researchers found in their review.

Complicating the Drexel study is the fact that nonfatal overdoses are typically under-reported and under-researched. It’s difficult to track overdoses outside of hospital visits, but Ataiants said that fatal overdoses likely represent only 3% to 4% of the total overdose toll.

Because of the lack of research around nonfatal overdoses, for now, the Drexel researchers’ conclusions on overdose and cognitive decline are “on the level of hypothesis,” Ataiants said. “We need to study this properly and do some prospective research.”

But, she says, the available research points to the fact that researchers and public health advocates need to think more about the health consequences of nonfatal overdoses. That includes incorporating the treatment and accommodation of neurological issues into overdose prevention strategies.

“We look at overdose risk factors, and we know a lot about it,” Ataiants said. “But I didn’t even think in the opposite direction -- how overdose can become a cause of degenerating health. We need to pay more attention to the health of overdose survivors.”