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Clinical Challenge: Pain and Cognition

Last updated: 03-13-2020

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Clinical Challenge: Pain and Cognition

Observational studies have looked at the relationship but "there's still a lot of unanswered questions," said Yuko Hara, PhD, of the Alzheimer's Drug Discovery Foundation in New York City. "We don't know whether there's a causal link -- in other words, whether chronic pain causes cognitive decline -- or whether there's just an association," she observed.

Chronic pain can affect cognitive function in many different ways, Hara noted. "Pain can increase levels of stress hormones like cortisol, which has been shown to affect brain structure, as well as structures of brain cells," she said. Pain can be "consuming and distracting and can make it more difficult for people to perform cognitive and memory tasks well," she continued. And pain can interfere with sleep, and "quality sleep is important for optimal cognitive function," she pointed out.

Moreover, depending on where the pain originates, "people with chronic pain may not be able to get enough physical exercise, which is one of the key lifestyle steps we recommend for cognitive health," she added. "There's strong evidence that exercisers are less likely to develop Alzheimer's disease."

In 2018, a group of researchers in France reviewed 24 observational studies about chronic pain and memory and found consistent reports of moderate decline in memory performance among people with chronic pain. Their results also showed that chronic pain selectively affected the most attention-demanding memory processes such as working memory and recollection in long-term memory, and that pain patients exhibited a memory bias directed towards painful events compared with controls.

Even studies of younger adults show that people with chronic pain perform worse on formal cognitive testing than people without pain, noted Elizabeth Whitlock, MD, MS, of the University of California, San Francisco.

Among older people, the consequences can be serious. Chronic pain affects millions of older adults who "are particularly likely not to recover from chronic pain compared with younger adults," Whitlock said.

To identify what may happen to older pain patients over time, Whitlock and other researchers tracked data from the Health and Retirement Study, a longitudinal survey of 10,065 older adults. Every 2 years, participants answered questions about pain and cognition and other factors.

The researchers looked at two groups: 1,120 individuals who reported moderate to severe pain in both the 1998 and 2000 surveys (defined as people with persistent pain), and everyone else. At baseline, persistent pain was associated with worse depressive symptoms and more limitations in activities of daily living.

Over time, people with persistent pain experienced a 9.2% more rapid decline in memory score, which translated to a relative 11.8% to 15.9% increased risk of inability to manage medications or finances independently at the end of 10 years, compared with age-adjusted Health and Retirement Study peers.

"With this work, we showed that older adults with persistent pain have a faster rate of cognitive decline than those who do not, and that this may translate to an increased risk of dementia in late life," Whitlock said.

"It's important to recognize that the cognitive decline we saw in our study population of older Americans may be directly caused by chronic pain -- in which case treating the pain would improve cognition -- or it might be because of other factors," she added. "For example, many people with chronic pain use opioids and other medications to manage their pain which have brain-related side effects; those could be part of the effect we see."

"But even if the cognitive decline we see in older adults with persistent pain is due to factors that we can't change, we found a high prevalence of depression and functional limitations in older adults who reported pain in our study," Whitlock noted.

Asking patients about chronic pain not only starts a discussion about pain management, but also presents an opportunity to introduce mitigation strategies, Whitlock noted. "Pain, and chronic pain, can serve as an opportunity for primary care providers to open a conversation about cognition, function, mood, and life goals, helping center a physician's thinking around some real challenges to quality of life as we age," she said.

"Since cognition is intimately tied to function and independence for older adults, one potential application of these findings is that those with chronic pain who perceive cognitive challenges could ask their physicians about assistive strategies like 'pill packs' or targeted deprescribing for those with complex and hard-to-manage medication regimens," she continued. "It's also important to plan for a future which may include faster cognitive decline by involving family and close caregivers and eliciting, for example, care preferences early," she added.

How pain and cognition are intertwined remains a mystery, but in one chronic condition -- neuropathic pain -- scientists may be making progress. Last year, University of Texas at Dallas (UT Dallas) researchers pinpointed a single biochemical pathway for both neuropathic pain and cognitive problems in mice, showing that abnormal protein synthesis in damaged nerve cells may drive pain signals and alter brain-cell structure.

"We're getting closer to knowing how executive deficit happens with neuropathic pain," UT Dallas researcher Theodore Price, PhD, said in a statement. "Human imaging studies show that the prefrontal cortex, which is involved with decision-making and attention, gets smaller in neuropathic pain sufferers through a process called cortical thinning."

Treating pain does not solve the problem, but it's possible that targeting mitogen-activated protein kinase-interacting kinase could, the researchers noted.

"One problem with existing pain medicine is that it only manages symptoms. What we really need are disease-modifying therapies," Price said. "I'm pretty convinced that this target has that potential."


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