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Widespread Pain May Predict Dementia and Alzheimer’s Disease

September 29, 2021
Chronic pain has been proposed as an early indicator of cognitive decline. A new study finds associations between widespread pain and adverse cognitive outcomes – as well as stroke – at the population level.

Widespread pain was associated with a significant increase in all-cause dementia, Alzheimer’s disease, and stroke, based on data from approximately 2,500 adults enrolled in the Framingham Heart Study (FHS). The FHS is an ongoing longitudinal, multigenerational study in residents of the city of Framingham, Massachusetts that has included the spinoff Framingham Offspring Study Cohort since 1970. This subset includes 5,124 Caucasian individuals who were the children of the original study participants and undergo health assessments every four years. The current study used data from the Framingham Offspring Study Cohort who were examined between 1990 and 1994 with detailed pain data.

Over a 10-year follow-up period, widespread pain was associated with increased risk of dementia, Alzheimer’s disease, and stroke (Image: iStock).

As the global population ages, dementia is becoming a worldwide public health issue, wrote Kanran Wang, MD, and Hong Liu, MD, of First Affiliated Hospital of Chongqing Medical University, China. “Early detection of persons at risk for dementia in particular might enable better targeting of potential disease-modifying therapies and, thus, improve outcomes,” they said in their study, published in Regional Anesthesia & Pain Medicine.1

Widespread Pain Linked to Cognitive Decline and Stroke

Using data from the United States community-based Framingham Heart Study, Drs. Wang and Liu assessed pain status of individuals at a single time point between 1990 and 1994. Participants were followed and assessed for incident dementia, Alzheimer’s disease (AD) and stroke a median of 10 years later.

A total of 347 participants met criteria for widespread pain at the start of the study while 2,117 did not. Widespread pain was defined in the Framingham study as “pain above and below the waist, on the left and right-hand sides of the body and in the axial skeleton according to the American College of Rheumatology criteria.”1 Previous studies suggest that chronic pain may be an early indicator of cognitive decline, but none has examined associations between widespread pain and adverse cognitive outcomes and stroke at the population level, they noted.

Over a 10-year follow-up period, widespread pain was associated with:

  • a 43% increased risk of all-cause dementia
  • a 47% increased risk of Alzheimer’s disease
  • a 29% increased risk of stroke in multivariate analysis

During the follow-up period, 188 individuals developed dementia or AD (50 with widespread pain and 138 without) and 139 individuals suffered a stroke, 31 with widespread pain and 108 without.

The associations were independent of variables including age, health, and sociodemographic factors, and results were similar in a subgroup of participants older than 65 years.

“The persistent difficulty of determining who is at high risk for dementia has led to intense interest in identifying disease conditions that predict the onset of dementia, AD dementia, and stroke,” Dr. Liu told PPM. “It remains unclear what aspects of widespread pain (WSP) should be targeted,” he said. Dr. Liu added that he was surprised by the association between widespread pain and increased risk of dementia, AD dementia, and stroke.

“Clinicians should be made aware of these associations and seek earlier diagnosis to provide timely therapies for better outcomes,” he said.

Causes of Cognitive Decline and Stroke in People with Chronic Pain

The researchers presented three possible factors behind the increased risk for stroke or dementia among individuals with widespread pain.

  1. First, individuals with widespread pain may be more likely to have a less healthy lifestyle, with low levels of physical activity, poor diet, and depression, all of which have been associated with developing dementia.
  2. Second, they suggested that widespread pain may cause direct impairment of cognitive function by competing directly for cognitive processing resources in the brain.
  3. Finally, they noted previous research showing that “chronic pain may result in decreases in gray and white matter in the brain, which could ultimately influence the development of depression, anxiety and loss of cognition,” and could be considered a preclinical phase of dementia and AD.

The study findings were limited by several factors including the observational design and the homogenous study population, as well as the small number of incident events and potential for selection bias, the researchers noted. However, the results were strengthened by the population-based cohort, long study period, and accurate assessment of dementia and stroke, they clarified.

“Notably, this study is, to our knowledge, the first to assess the association between [widespread pain], dementia, and stroke, incorporating a detailed review of medical records and autopsies to minimize the error rates on the incidence and the influence of confounders,” they added.

Practical Takeaways: How High is the Risk of Stroke or Dementia in Pain Populations?

“Pain is a huge threat to quality of life at any age, and we are increasingly appreciating the fact that chronic or persistent pain, or widespread pain as in this study, may be a marker for other serious problems that arise in late life,” said Elizabeth Whitlock, MD, an assistant professor of anesthesia at the University of California, San Francisco, in an interview.

“Maintenance of cognitive health is a high priority for older adults, because it is so closely tied to independence, and this study elaborates on some complex interactions between pain, cognition, and other health characteristics,” she said. “This work fits well into existing literature about pain and faster cognitive decline in later life, although previous studies have generally found that the increase in cognitive decline is subtle. This study used rigorous measurements of pain and dementia outcomes and leveraged an impressively long follow-up time, which may explain why they were able to detect a relationship between pain and later dementia. Dementia, particularly vascular dementia, and stroke have many risk factors in common, so it is not surprising, but of course, it is worrisome, that stroke risk was higher in the people with pain, too.”

However, Dr. Whitlock emphasized that the take-home message for clinicians is not that all people with chronic pain will experience strokes or dementia. “The relationship here, as with other studies, isn’t extremely strong,” she said. “A 50% increased risk may sound high, but as far as predicting who will get dementia or have a stroke, it isn’t strong enough as a single factor to be helpful,” she noted.

However, “this work adds to a body of literature that shows that pain probably works in tandem with other risk factors—in this case, health factors such as diabetes and depression, and social factors such as low income, unemployment, and lower level of education—to increase risk for bad outcomes later in life that older adults may not have the resilience to manage,” she concluded.

Widespread Pain Outcomes: Can Cognitive Decline Be Prevented?

Additional research is needed, Dr. Whitlock emphasized. “The big question is, of course, how much of these negative outcomes can be prevented. If we successfully treat widespread pain (for which there are no universally effective or available treatments), will people's late-life cognition and cerebrovascular health be better?” she speculated. “The study authors discuss that widespread pain may reflect a constellation of mid-life risk factors that are associated with, but do not directly cause, late-life adverse outcomes,” explained Dr. Whitlock.

“In that case, perhaps efforts to address late-life cognition should begin in midlife, with helping people manage not only pain syndromes but also depression and social risk factors. Other early interventions might include supporting access to healthy food, lower barriers and costs of preventive healthcare for early-stage diabetes, and “more support and community for adults generally as they age.”

“We desperately need better safety nets for people with cognitive decline and dementia, but also with pain syndromes, and with depression, so we can support their quality of life and independence into old age,” said Dr. Whitlock. “This isn't flashy or fabulous like a new medication; it is the difficult work of caregiving and support and respite for caregivers, of providing resources to keep older adults mentally active, and of diagnosing and treating depression,” she said.

Disclosures: The study was supported by the First Affiliated Hospital of Chongqing Medical University, Chongqing, China and Chongqing Medical University Scholarship Fund for Development of Young Talents. The researchers had no financial conflicts to disclose. Dr. Whitlock had no financial conflicts to disclose. She was the lead author of a 2017 study published in JAMA Internal Medicine on the association between pain and memory decline and dementia.

Last updated on: October 8, 2021
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