Low Dose Opioids Do Not Raise Dementia Risk, But High Doses Might

By Crystal Lindell

There’s a new study out showing that low-dose opioids are not linked to an increased risk of developing dementia, but higher doses might. 

Researchers followed the health of over 1.8 million people in Denmark aged 60 to 75, about 5% of whom developed dementia. They tracked the opioid use of those with and without dementia to see what role, if any, opioids may have in causing cognitive decline.

They found that low dose opioids prescribed for chronic non-cancer pain — which they defined as up to 90 total standardized doses (TSDs) — was not consistently associated with dementia risk. However, doses above 90 TSD were associated with a slightly elevated dementia risk before age 90. 

Interestingly, the strongest association between opioids and dementia was found with “weak” opioids such as tramadol.

Total standardized doses are a different way of measuring opioid use than what is typically used in the United States. Medical guidelines in the U.S. focus on morphine milligram equivalents (MME) per day. Depending on the guideline, anything over 50 or 90 MME would be considered a high dose.   

For the Danish study, 1 TSD is the equivalent of 30 MME. So someone with a TSD of 90 is getting the equivalent of 2,700 MME over time. Researchers used this method because they wanted to see what the cumulative effect of opioids would have on dementia.  

“This study found that opioid use of less than 90 TSDs was not significantly associated with increased dementia risk. Above 90 TSDs of opioid use was associated with an elevated dementia risk before age 90 years, which persisted in individuals with chronic noncancer pain and in individuals solely exposed to weak opioids,” researchers reported in JAMA Network Open,.

They also added the favorite caveat of medical researchers everywhere: “Further research should ascertain whether the findings denote causality between opioids and dementia risk.” 

In other words, it is still unclear if taking higher doses of opioids leads to dementia, or if chronic pain puts people at higher risk of dementia. It’s a chicken and egg question without any answers. 

A previous study also found that high doses of opioids slightly raise the risk of dementia, but so did nonsteroidal anti-inflammatory drugs (NSAIDs). So switching someone from opioids to NSAID pain relievers won’t lower their risk.  

Regardless, given the findings in the Danish study about the lower doses, I am glad to see some more definitive evidence that opioids aren’t the cause of every ailment ever. 

I do worry that the study even existing will perpetuate harmful opioid-phobia myths though. For example, the study’s headline – “Opioids and Dementia in the Danish Population” – is just vague enough that casual readers may assume that the research did show a link between opioids and dementia, regardless of the dose. 

It also irks me that researchers included the favorite sentence of opioid-phobia propagandists: "Opioids are frequently used to treat chronic noncancer pain, but evidence of the effect on pain management and quality of life is lacking." 

As usual, the fact that millions of people around the world have told doctors that opioids help their pain is apparently not “evidence.” They can’t trust any of us.  

As someone who’s been on what the researchers would consider “low dose” opioids since I was 29 years old, I can tell you they do help manage my pain and give me a better quality of life. If the researchers found a higher dementia risk for me, I’d still keep taking opioids. 

Opioids are the only thing that allows me to live my life today. I’m not going to give that up because I might have a higher risk of dementia decades from now. In fact, if I did give them up, I suspect there’s a high chance that I would not make it into my senior years anyway, seeing as how opioids are often the only thing that makes my daily pain endurable. 

I suspect I’m not alone. Research like this is unlikely to deter most pain patients from taking opioids, but it could make some doctors hesitant to prescribe them. And that’s a shame. Because a study showing that low-dose opioids aren’t as bad as some feared should make doctors more comfortable prescribing them.

Neurological Conditions Now Leading Cause of Chronic Illness

By Pat Anson, PNN Editor

The number of people living with neurological conditions such as migraine, diabetic neuropathy, epilepsy, stroke and dementia has risen significantly over the past 30 years, making it the leading cause of chronic illness worldwide, according to a new analysis published in The Lancet Neurology.

An international research team estimates that over 3.4 billion people – about 43% of the global population – had a neurological condition in 2021, replacing cardiovascular disease as the leading cause of poor health.

“The worldwide neurological burden is growing very fast and will put even more pressure on health systems in the coming decades,” said co-author Valery Feigin, MD, Director of the National Institute for Stroke and Applied Neuroscience at Auckland University in New Zealand.

“Yet many current strategies for reducing neurological conditions have low effectiveness or are not sufficiently deployed, as is the case with some of the fastest-growing but largely preventable conditions like diabetic neuropathy and neonatal disorders. For many other conditions, there is no cure, underscoring the importance of greater investment and research into novel interventions and potentially modifiable risk factors.”

A total of 37 disorders affecting the brain and nervous system were included in the study. Collectively, the nerve disorders are responsible for 443 million years of healthy life lost due to illness, disability or premature death, known as disability-adjusted life years (DALYs).

Tension-type headaches (about 2 billion cases) and migraines (about 1.1 billion) are the two most common neurological disorders, while diabetic neuropathy is the fastest-growing one. Painful stinging or burning sensations in the nerves of the hands and feet are often the first symptoms of diabetes.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021,” said co-senior author Liane Ong, PhD, from the Institute for Health Metrics and Evaluation at University of Washington. “This is in line with the increase in the global prevalence of diabetes.”

Over 80% of neurological deaths and disability occur in low- and middle-income countries, with western and central sub-Saharan Africa having the highest DALY rates. In contrast, high-income countries in the Asian Pacific and Australasia regions had the lowest rates.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” said co-author Tarun Dua, MD, Unit Head of WHO’s Brain Health unit.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries.”

Medical providers specializing in neurological care are unevenly distributed around the world, with wealthy countries having about 70 times the number of specialists as low-income ones.

Researchers say prevention needs to be a top priority in addressing the growth of neurological conditions. Some disorders, such as stroke and chronic headache, are potentially preventable by lowering risk factors such as high blood pressure, smoking and alcohol use.

The study was funded by the Bill and Melinda Gates Foundation.

Can Cannabis Help Prevent Dementia?

By Pat Anson, PNN Editor

People use cannabis for a variety of reasons. Some use it to relieve pain. Others use it to help them sleep, improve their appetite, or reduce anxiety and stress. Still others use cannabis because it makes them feel good.

A new study suggests there’s another unexpected benefit from consuming cannabis, especially when it’s used recreationally: It may help middle-aged adults ward of dementia.

Researchers at SUNY Upstate Medical University looked at health survey data that assessed the subjective cognitive decline (SCD) of over 4,700 U.S. adults between the ages of 45 and 64. Memory loss and confusion are symptoms of SCD, which is considered an early sign of dementia.

To their surprise, researchers found that participants who only used cannabis recreationally had significantly lower risk of SCD – as much as 96% less risk compared to non-users. Those who used cannabis for medical reasons or combined it with recreational use also had lower odds of SCD, but the difference was not statistically significant.

“We found that non-medical cannabis use was significantly associated with reduced odds of SCD in comparison to non-users. Several factors might explain this observation. Non-medical use of cannabis often contains THC, which has a psychoactive component that creates the ‘high’ sensation. Whereas CBD is non-psychoactive and often used for anxiety and chronic pain management,” the SUNY research team recently reported in the journal Current Alzheimer Research.

One likely reason for the disparity in SCD between recreational and medical users is that those who consume cannabis for health reasons may have comorbid medical conditions – such as diabetes, hypertension, cardiovascular disease and musculoskeletal disorders -- that raise their risk of dementia.

Another consideration is sleep. One of the primary reasons people use cannabis is to help them fall asleep faster and stay asleep longer. Recreational use of cannabis has the added benefit of improving sleep quality. A recent study found that insomnia is associated with a 51% higher risk of dementia risk.

The frequency of cannabis use and whether it was smoked, vaped or ingested had no significant connection to SCD risk.

Although the study found no direct cause-and-effect relationship between cannabis, SCD and dementia, researchers think it’s worth exploring further. More than six million Americans have Alzheimer’s disease or some form of dementia, a number that’s expected to double by 2050. 

“Despite the advancement of medicine and technology, dementia remains incurable and non-preventable. While some medications can slow symptom progression, they are only effective if started during early stages and cannot reverse its course,” SUNY researchers concluded. “Given the widespread use of cannabis in the U.S., it is imperative to pursue further research to understand the mechanism underlying the reduced odds of SCD among non-medical cannabis users.”

Family Caregivers Face Financial Burdens, Isolation and Burnout

By Dr. Kathy Lee, University of Texas at Arlington

Millions of Americans have become informal family caregivers: people who provide family members or friends with unpaid assistance in accomplishing daily tasks such as bathing, eating, transportation and managing medications.

Driven in part by a preference for home-based care rather than long-term care options such as assisted living facilities, and the limited availability and high cost of formal care services, family caregivers play a pivotal role in the safety and well-being of their loved ones.

Approximately 34.2 million people in the United States provide unpaid assistance to adults age 50 or above, according to the Family Caregiver Alliance. Among them, about 15.7 million adult family caregivers care for someone with dementia.

Help celebrate National Caregivers Day (Feb. 16) by thanking someone who cares for a disabled loved one.

Challenging Situations

I am a licensed clinical social worker and an assistant professor of social work studying disparities in health and health care systems. I focus on underrepresented populations in the field of aging.

In my research focusing on East Asian family caregivers for people with Alzheimer’s and related dementia, I discovered that Chinese American and Korean American caregivers often encounter challenging situations. These include discrimination from health care facilities or providers, feelings of loneliness and financial issues. Some of these caregivers even find themselves having to retire early because they struggle to balance both work and caregiving responsibilities.

My findings join a growing body of research showing that family caregivers commonly encounter five specific challenges: financial burdens, limited use of home- and community-based services, difficulties accessing resources, a lack of knowledge about existing educational programs, and physical and emotional challenges, such as feelings of helplessness and caregiver burnout.

However, researchers are also finding that family caregivers feel more capable of managing these challenges when they can tap into formal services that offer practical guidance and insights for their situations, as well as assistance with some unique challenges involved with family caregiving.

Most Caregivers Are Women

More than 6 in 10 family caregivers are women.

Society has always expected women to take on caregiving responsibilities. Women also usually earn less money or rely on other family members for financial support. This is because equal pay in the workplace has been slow to happen, and women often take on roles like becoming the primary caregiver for their own children as well as their aging relatives, which can drastically affect their earnings.

While nearly half of care recipients live in their own homes, 1 in 3 live with their caregivers.

Sometimes termed “resident caregivers,” these individuals are less likely to turn to others outside the family for caregiving support, often because they feel that it’s important to keep caregiving within the family. These caregivers are typically older, retired or unemployed and have lower income than caregivers who live separately.

According to a 2020 report from the AARP Public Policy Institute, about 1 in 3 family caregivers provide more than 21 hours of care a week to a loved one.

Support Programs for Caregivers

Caregiving often creates financial burdens because it makes it harder to hold a full-time or part-time job, or to return to work after taking time off, particularly for spouses who are caregivers.

Often, community-based organizations such as nonprofits that serve older adults offer a variety of in-home services and educational programs. These can help family caregivers manage or reduce the physical and emotional strains of their responsibilities. However, these demands also can make it difficult for some caregivers to even learn that these resources exist, or take advantage of them, particularly as the care recipient’s condition progresses.

These challenges worsened at the height of the COVID-19 pandemic. Many support programs were canceled, and it was hard to access health care, which made things even more stressful and tiring for caregivers.

Research shows that those who are new to family caregiving often take care of their loved ones without any formal support initially. As a result, they may face increased emotional burdens. And caregivers age 70 and above face particular challenges, since they may be navigating their own health issues at the same time. These individuals are less likely to receive informal support, which can lead to social isolation and burnout. 

There are numerous programs and services available for family caregivers and their loved ones, whether they reside at home or in a residential facility. These resources include government health and disability programs, legal assistance and disease-specific organizations, some of which are specific to certain states.

In addition, research has found that providing appropriate education and training to people in the early stages of caregiving enables them to better balance their own health and well-being with successfully fulfilling their responsibilities. Many community-based organizations, such as local nonprofits focused on aging, as well as government programs or senior centers, may offer case management services for older adults, which can be beneficial for learning about existing resources and services.

For family caregivers of people with dementia, formal support services are particularly crucial to their ability to cope and navigate the challenges they face.

Formal support may also be helpful in finding affordable home-based and community resources that can help compensate for a lack of informal support. These include home health services funded by Medicare and Medicaid-funded providers of medical and nonmedical services, including transportation.

Medicaid, which targets low-income Americans, seniors, people with disabilities and a few select other groups, has certain income requirements. Determine the eligibility requirements first to find out whether your loved one qualifies for Medicaid.

The services and support covered by Medicaid may vary based on a number of factors, such as timing of care, the specific needs of caregivers and their loved ones, the care plan in place for the loved one and the location or state in which the caregiver and their loved one reside.

Each state also has its own Medicaid program with unique rules, regulations and eligibility criteria. This can result in variations in the types of services covered, the extent of coverage and the specific requirements for accessing Medicaid-funded support.

If so, contact your state’s Medicaid office to get more information about self-directed services and whether you can become a paid family caregiver.

Medicare may help pay for certain home health services if an older adult needs skilled services part time and is considered homebound.

This assistance can alleviate some of the caregiving responsibilities and financial burdens on the family caregiver, allowing them to focus on providing care and support to their loved ones without worrying about the cost of essential medical services.

Peer-to-peer support is also crucial. Family caregivers who join support groups tend to manage their stress more effectively and experience an overall better quality of life.

Kathy Lee, PhD, is an Assistant Professor of Gerontological Social Work at University of Texas at Arlington. Her primary focus lies in exploring innovative and non-pharmacological interventions for individuals living with Alzheimer's disease and related dementias, as well as providing support for their family caregivers.

This article originally appeared in The Conversation  and is republished with permission.

Long Covid Symptoms Often Overlooked in Seniors

By Judith Graham, Kaiser Health News

Nearly 18 months after getting covid-19 and spending weeks in the hospital, Terry Bell struggles with hanging up his shirts and pants after doing the laundry.

Lifting his clothes, raising his arms or arranging items in his closet leave Bell short of breath and often trigger severe fatigue. He walks with a cane, only short distances. He’s 50 pounds lighter than when the virus struck.

Bell, 70, is among millions of older adults who have grappled with long covid — a population that has received little attention even though research suggests seniors are more likely to develop the poorly understood condition than younger or middle-aged adults.

Long covid refers to ongoing or new health problems that occur at least four weeks after a covid infection, according to the Centers for Disease Control and Prevention. Much about the condition is baffling: There is no diagnostic test to confirm it, no standard definition of the ailment, and no way to predict who will be affected.

Common symptoms, which can last months or years, include fatigue, shortness of breath, an elevated heart rate, muscle and joint pain, sleep disruptions, and problems with attention, concentration, language, and memory — a set of difficulties known as brain fog.

Ongoing inflammation or a dysfunctional immune response may be responsible, along with reservoirs of the virus that remain in the body, small blood clots, or residual damage to the heart, lungs, vascular system, brain, kidneys, or other organs.

Only now is the impact on older adults beginning to be documented. In the largest study of its kind, published recently in the journal BMJ, researchers estimated that 32% of older adults in the U.S. who survived covid infections had symptoms of long covid up to four months after infection — more than double the 14% rate an earlier study found in adults ages 18 to 64. Other studies suggest symptoms can last much longer, for a year or more.

The BMJ study examined more than 87,000 adults 65 and older who had covid infections in 2020, drawing on claims data from UnitedHealth Group’s Medicare Advantage plans. It included symptoms that lasted 21 days or more after an infection, a shorter period than the CDC uses in its long covid definition. The data encompasses both older adults who were hospitalized because of covid (27%) and those who were not (73%).

The higher rate of post-covid symptoms in older adults is likely due to a higher incidence of chronic disease and physical vulnerability in this population — traits that have led to a greater burden of serious illness, hospitalization, and death among seniors throughout the pandemic.

“On average, older adults are less resilient. They don’t have the same ability to bounce back from serious illness,” said Dr. Ken Cohen, a co-author of the study and executive director of translational research for Optum Care, a network of physician practices owned by UnitedHealth Group.

“The challenge is that nonspecific symptoms such as fatigue, weakness, pain, confusion, and increased frailty are things we often see in seriously ill older adults.”

— Dr. Charles Semelka

Applying the study’s findings to the latest data from the CDC suggests that up to 2.5 million older adults may have been affected by long covid. For those individuals, the consequences can be devastating: the onset of disability, the inability to work, reduced ability to carry out activities of daily life, and a lower quality of life.

But in many seniors, long covid is difficult to recognize.

“The challenge is that nonspecific symptoms such as fatigue, weakness, pain, confusion, and increased frailty are things we often see in seriously ill older adults. Or people may think, ‘That’s just part of aging,’” said Dr. Charles Thomas Alexander Semelka, a postdoctoral fellow in geriatric medicine at Wake Forest University.

Ann Morse, 72, of Nashville, Tennessee, was diagnosed with covid in November 2020 and recovered at home after a trip to the emergency room and follow-up home visits from nurses every few days. She soon began having trouble with her memory, attention and speech, as well as sleep problems and severe fatigue. Though she’s improved somewhat, several cognitive issues and fatigue persist to this day.

“What was frustrating was I would tell people my symptoms and they’d say, ‘Oh, we’re like that too,’ as if this was about getting older,” she told me. “And I’m like, but this happened to me suddenly, almost overnight.”

Bell, a singer-songwriter in Nashville, had a hard time getting adequate follow-up attention after spending two weeks in intensive care and an additional five weeks in a nursing home receiving rehabilitation therapy.

“I wasn’t getting answers from my regular doctors about my breathing and other issues. They said take some over-the-counter medications for your sinus and things like that,” he said. Bell said his real recovery began after he was recommended to specialists at Vanderbilt University Medical Center.

Long Covid and Dementia

James Jackson, director of long-term outcomes at Vanderbilt’s Critical Illness, Brain Dysfunction, and Survivorship Center, runs several long covid support groups that Morse and Bell attend and has worked with hundreds of similar patients. He estimates that about a third of those who are older have some degree of cognitive impairment.

“We know there are significant differences between younger and older brains. Younger brains are more plastic and effective at reconstituting, and our younger patients seem able to regain their cognitive functioning more quickly,” he said.

In extreme cases, covid infections can lead to dementia. That may be because older adults who are severely ill with covid are at high risk of developing delirium — an acute and sudden change in mental status — which is associated with the subsequent development of dementia, said Dr. Liron Sinvani, a geriatrician and an assistant professor at Northwell Health’s Feinstein Institutes for Medical Research in Manhasset, New York.

Older patients’ brains also may have been injured from oxygen deprivation or inflammation. Or disease processes that underlie dementia may already have been underway, and a covid infection may serve as a tipping point, hastening the emergence of symptoms.

Research conducted by Sinvani and colleagues, published in March, found that 13% of covid patients who were 65 and older and hospitalized at Northwell Health in March 2020 or April 2020 had evidence of dementia a year later.

Dr. Thomas Gut, associate chair of medicine at Staten Island University Hospital, which opened one of the first long covid clinics in the U.S., observed that becoming ill with covid can push older adults with preexisting conditions such as heart failure or lung disease “over the edge” to a more severe impairment.

“It’s hard to attribute what’s directly related to covid and what’s a progression of conditions they already have,” said Gut.

That wasn’t true for Richard Gard, 67, who lives just outside New Haven, Connecticut, a self-described “very healthy and fit” sailor, scuba diver, and music teacher at Yale University who contracted covid in March 2020. He was the first covid patient treated at Yale New Haven Hospital, where he was critically ill for 2½ weeks, including five days in intensive care and three days on a ventilator.

In the two years since, Gard has spent more than two months in the hospital, usually for symptoms that resemble a heart attack. “If I tried to walk up the stairs or 10 feet, I would almost pass out with exhaustion, and the symptoms would start — extreme chest pain radiating up my arm into my neck, trouble breathing, sweating,” he said.

Dr. Erica Spatz, director of the preventive cardiovascular health program at Yale, is one of Gard’s physicians. “The more severe the covid infection and the older you are, the more likely it is you’ll have a cardiovascular complication after,” she said. Complications include weakening of the heart muscle, blood clots, abnormal heart rhythms, vascular system damage, and high blood pressure.

Gard’s life has changed in ways he never imagined. Unable to work, he takes 22 medications and can still walk only 10 minutes on level ground. Post-traumatic stress disorder is a frequent, unwanted companion.

“A lot of times it’s been difficult to go on, but I tell myself I just have to get up and try one more time,” he told me. “Every day that I get a little bit better, I tell myself I’m adding another day or week to my life.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Widespread Pain Raises Risk of Dementia and Stroke

By Pat Anson, PNN Editor

Widespread body pain caused by fibromyalgia and other chronic pain conditions raises the risk of stroke and dementia, including Alzheimer’s disease, according to a new study.

Researchers looked at health data for nearly 2,500 second generation participants in the long-running, community-based Framingham Heart Study. Participants in the “offspring” phase of the study were given a comprehensive check-up that included a physical exam, lab tests and detailed pain assessment when they enrolled in the early 1990’s. They were then reassessed every four years for signs of cognitive decline, dementia or stroke.

Over the next two decades, 188 of the participants were diagnosed with some form of dementia and 139 had a stroke.

While the number of cases was small, researchers found an association between pain and cognitive decline. Participants with widespread pain were 43% more likely to have some type of dementia, 47% more likely to have Alzheimer’s disease, and 29% more likely to have a stroke compared to those without widespread pain (WSP). 

“These findings provide convincing evidence that WSP may be a risk factor for all-cause dementia, AD dementia (Alzheimer’s), and stroke,” researchers concluded. “While it is known that chronic pain or persistent pain without detailed classification is associated with poorer cognitive performance in cross-sectional or cohort studies, our study was based on much more accurate assessments for pain at a longitudinal population level. The specific presence of WSP… has long-term implications for dementia and AD.”

The researchers said there were three possible explanations for the link between pain and cognitive decline. First are lifestyle factors associated with pain, such as reduced physical activity, poor diet, alcohol and weight gain. Second is that stress caused by widespread pain may impair cognitive function; and third is that WSP may be a “preclinical phase” of dementia and AD.

Previous studies have also linked chronic pain to dementia. A large 2017 study found that older people with chronic pain experience faster declines in memory and are more likely to develop dementia. A more recent study suggests that people with chronic pain are at higher risk of memory loss and cognitive decline if they have lower levels of education, income and access to healthcare.

Antidepressants, anti-psychotics, antihistamines and other common medications may also cause confusion and disorientation that is mistaken for dementia, especially in older adults. When patients are taken off the drugs, their cognitive function may improve.  

Previous studies have also linked widespread pain to cancer, peripheral arterial disease, cardiovascular disease and increased mortality.

Chronic Pain Linked to Memory Loss in Some Older Adults

By Pat Anson, PNN Editor

A new study suggests that people who live with chronic pain may be at higher risk of memory loss and cognitive decline if they have lower levels of education, income and access to healthcare.

The study by researchers at the University of Florida, published in the Journal of Alzheimer’s Disease, involved 147 adults between the ages of 45 and 85 who had mild to moderate knee pain. Participants enrolled in the study were asked to provide sociodemographic information, complete an assessment of their cognitive function, and have MRI brain scans.

People with higher pain levels who had low levels of income and education, and less access to health insurance had about 4% less gray matter in the temporal lobe of their brains (the area shaded in blue) compared to people with low pain levels who had more income and education, and greater access to healthcare.

“As we get older, typically starting around our mid-50s to mid-60s, we lose about half a percent of our gray matter per year,” said lead author Jared Tanner, PhD, an assistant professor of clinical and health psychology in the UF College of Public Health and Health Professions. “So a 3-4% difference could be thought of as an additional six to eight years of aging in the brain.”

The thinning of gray matter is predictive of future cognitive decline and greater risk of developing dementia or Alzheimer’s disease.

Tanner and his colleagues have been investigating how chronic pain acts as a stressor that causes physiological changes in humans. Other researchers have found that Black adults are up to twice as likely as White adults to develop Alzheimer’s disease. The new findings indicate a variety of environmental factors might be involved, including access to healthcare.

“This study helps us begin to identify an additional factor to explore that may contribute to health disparities in rates of dementia and Alzheimer’s disease in some underrepresented ethnic/race groups. In this case, it looks like stage of chronic pain, along with other life experiences, may be playing a role,” said Tanner.

“The body and the brain are adaptive to stress to a certain point,” said senior author Kimberly Sibille, PhD, an associate professor of aging & geriatric research and pain medicine in the UF College of Medicine. “But with persistent stressors that are more intense and longer duration, eventually the body’s response is no longer adaptive and changes start occurring in the other direction, a process known as allostatic overload. 

“People with low pain stage — intermittent, low intensity, shorter duration and minimal sites of pain — differ from the groups with higher stages of chronic pain. Further, in combination with lower protective factors, including lower income, education and health insurance access, those individuals with higher chronic pain stage show less gray matter in cortical areas of the brain.”

A large 2017 study found that people aged 60 and older with chronic pain had faster declines in memory and cognitive ability than those who were not troubled by pain.

The brain may be able to regain some of its ability to function normally. A 2009 study of osteoarthritis patients showed a reversal in brain changes when their pain was adequately treated. 

Chronic Pain Accelerates Dementia

By Dr. Lynn Webster, PNN Columnist

In 2017, JAMA Internal Medicine published a study that found older people with chronic pain experience faster declines in memory and are more likely to develop dementia.  While prior research had shown a link between chronic pain and brain damage, this was one of the first studies to specifically suggest that chronic pain can cause dementia.

The authors reported that people aged 60 and over with persistent pain experienced a 9.2% more rapid decline in memory score when compared to people of the same age without chronic pain. This means that people with chronic pain may experience more difficulty in managing their finances, medications and social connections.

Dementia is a chronic condition of the brain that involves memory, personality and judgment. It is not a disease; it is a symptom of one or more diseases.

There are many types of dementia. Alzheimer’s disease is considered to be the most common.

Dementia usually worsens over time if the underlying disease remains static or progresses, as is the case with many chronic pain conditions.

There are an estimated 20 million Americans with high impact (the most severe) chronic pain who may be experiencing accelerated decline in cognition due to their pain. The amount of dementia appears to be associated with the severity and duration of chronic pain. Undertreated or untreated chronic pain may accelerate dementia.

Chronic pain affects an even larger percentage of elderly adults (one in three) than the general population. Since the prevalence of chronic pain increases with age, the probability of experiencing dementia increases as well. However, the reasons for that go beyond aging itself.

Seniors are more likely to take multiple medications that can contribute to mental confusion. On average, elderly people take five or more prescriptions. They may also use over-the-counter medications, which adds to potential drug-associated mental compromise.

Opioids, in particular, have been implicated in cognitive impairment. However, a study published in 2016 suggests there is no difference in cognitive decline between people on opioids and those on nonsteroidal anti-inflammatory drugs. The study's implication is that pain, not opioids, leads to cognitive impairment.

Brain Fog

Chronic pain appears to affect the function and structure of the hippocampus. This is the region of the brain that involves learning, memory, and emotional processing.

One explanation for the mental decline associated with chronic pain is that various areas of the brain compete for attention. Attentional impairment compromises memory by diverting attention to the areas of the brain processing pain. In effect, the brain is multi-tasking and favoring the processing of pain over cognition. This may, in part, explain the clinical phrase “brain fog.”

The Australian Broadcasting Company's "All in the Mind" website explains that pain damages the brain in several ways, including a change in the size of the thalamus and a decrease in the amount of a neurotransmitter (gamma-aminobutyric acid) the brain produces. In other words, chronic pain changes the brain structurally and functionally.

The prefrontal cortex is the part of the brain responsible for executive functions, such as cognition, social behavior, personality, and decision-making. It is also the part of the brain that modulates pain.

According to "All in the Mind," some researchers believe that chronic pain decreases the volume of the prefrontal cortex. Over time, brains damaged by pain lose the ability to handle pain — along with some of the personality attributes that make us who we are.

Brain Damage Can Be Reversed

The good news is that the brain damage caused by chronic pain can be reversed, at least to some extent. Unfortunately, the elderly are less likely to recover from dementia caused by chronic pain as compared with younger patients.

If pain is adequately treated, the brain may be able to regain its ability to function normally. A 2009 study of patients with chronic pain due to hip osteoarthritis showed reversal of brain changes when their pain was adequately treated. 

People who don’t have their acute pain managed are more likely to develop chronic pain. It is postulated that the changes in the brain that occur with chronic pain begin with the onset of acute pain. There is also some evidence that an individual’s genes may influence who is at greatest risk for developing brain damage from chronic pain and who is least likely to recover from it. 

Many people have criticized the concept of assessing pain as the 5th vital sign, and have called it a contributing factor for the opioid crisis. As I have said, pain may not be a vital sign, but it is vital that we assess it. Asking patients about their pain is critical to providing interventions that can mitigate the consequences of undertreated pain, including dementia. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD. 

The information in this column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Common Meds Can Cause Cognition Problems in Seniors

By Judith Graham, Kaiser Health News

By all accounts the woman, in her late 60s, appeared to have severe dementia. She was largely incoherent. Her short-term memory was terrible. She couldn’t focus on questions that medical professionals asked her.

But Dr. Malaz Boustani, a professor of aging research at Indiana University School of Medicine, suspected something else might be going on. The patient was taking Benadryl for seasonal allergies, another antihistamine for itching, Seroquel (an antipsychotic medication) for mood fluctuations, as well as medications for urinary incontinence and gastrointestinal upset.

To various degrees, each of these drugs blocks an important chemical messenger in the brain, acetylcholine. Boustani thought the cumulative impact might be causing the woman’s cognitive difficulties.

He was right. Over six months, Boustani and a pharmacist took the patient off those medications and substituted alternative treatments. Miraculously, she appeared to recover completely. Her initial score on the Mini-Mental State Exam had been 11 of 30 — signifying severe dementia — and it shot up to 28, in the normal range.

An estimated 1 in 4 older adults take anticholinergic drugs — a wide-ranging class of medications used to treat allergies, insomnia, leaky bladders, diarrhea, dizziness, motion sickness, asthma, Parkinson’s disease, chronic obstructive pulmonary disease and various psychiatric disorders.

Older adults are highly susceptible to negative responses to these medications. Since 2012, anticholinergics have been featured prominently on the American Geriatrics Society Beers Criteria list of medications that are potentially inappropriate for seniors.

“The drugs that I’m most worried about in my clinic, when I need to think about what might be contributing to older patients’ memory loss or cognitive changes, are the anticholinergics,” said Dr. Rosemary Laird, a geriatrician and medical director of the Maturing Minds Clinic at AdventHealth in Winter Park, Fla.

Here’s what older adults should know about these drugs:

The Basics

Anticholinergic medications target acetylcholine, an important chemical messenger in the parasympathetic nervous system that dilates blood vessels and regulates muscle contractions, bodily secretions and heart rate, among other functions. In the brain, acetylcholine plays a key role in attention, concentration, and memory formation and consolidation.

Some medications have strong anticholinergic properties, others less so. Among prescription medicines with strong effects are antidepressants such as imipramine (brand name Trofanil), antihistamines such as hydroxyzine (Vistaril and Atarax), antipsychotics such as clozapine (Clozaril and FazaClo), antispasmodics such as dicyclomine (Bentyl) and drugs for urinary incontinence such as tolterodine (Detrol).

In addition to prescription medications, many common over-the-counter drugs have anticholinergic properties, including antihistamines such as Benadryl and Chlor-Trimeton and sleep aids such as Tylenol PM, Aleve PM and Nytol.

Common side effects include dizziness, confusion, drowsiness, disorientation, agitation, blurry vision, dry mouth, constipation, difficulty urinating and delirium, a sudden and acute change in consciousness.

Unfortunately, “physicians often attribute anticholinergic symptoms in elderly people to aging or age-related illness rather than the effects of drugs,” according to a research review by physicians at the Medical University of South Carolina and in Britain.

Seniors are more susceptible to adverse effects from these medications for several reasons: Their brains process acetylcholine less efficiently. The medications are more likely to cross the blood-brain barrier. And their bodies take longer to break down these drugs.

Long-Term Effects

In the late 1970s, researchers discovered that deficits in an enzyme that synthesizes acetylcholine were present in the brains of people with Alzheimer’s disease. “That put geriatricians and neurologists on alert, and the word went out: Don’t put older adults, especially those with cognitive dysfunction, on drugs with acetylcholine-blocking effects,” said Dr. Steven DeKosky, deputy director of the McKnight Brain Institute at the University of Florida.

Still, experts thought that the effects of anticholinergics were short-term and that if older patients stopped taking them, “that’s it — everything goes back to normal,” Boustani said.

Concerns mounted in the mid-2000s when researchers picked up signals that anticholinergic drugs could have a long-term effect, possibly leading to the death of brain neurons and the accumulation of plaques and tangles associated with neurodegeneration.

Since then several studies have noted an association between anticholinergics and a heightened risk of dementia. In late June, this risk was highlighted in a new report in JAMA Internal Medicine that examined more than 284,000 adults age 55 and older in Britain between 2004 and 2016.

The study found that more than half of these subjects had been prescribed at least one of 56 anticholinergic drugs. (Multiple prescriptions of these drugs were common as well.) People who took a daily dose of a strong anticholinergic for three years had a 49% increased risk of dementia. Effects were most pronounced for people who took anticholinergic antidepressants, antipsychotics, antiepileptic drugs and bladder control medications.

These findings don’t constitute proof that anticholinergic drugs cause dementia; they show only an association. But based on this study and earlier research, Boustani said, it now appears older adults who take strong anticholinergic medications for one to three years are vulnerable to long-term side effects.

Preventing Harm

Attention is now turning to how best to wean older adults off anticholinergics, and whether doing so might improve cognition or prevent dementia.

Researchers at Indiana University’s School of Medicine hope to answer these questions in two new studies, starting this fall, supported by $6.8 million in funding from the National Institute on Aging.

One will enroll 344 older adults who are taking anticholinergics and whose cognition is mildly impaired. A pharmacist will work with these patients and their physicians to take them off the medications, and patients’ cognition will be assessed every six months for two years.

The goal is to see whether patients’ brains “get better,” said Noll Campbell, a research scientist at Indiana University’s Regenstrief Institute and an assistant professor at Purdue University’s College of Pharmacy. If so, that would constitute evidence that anticholinergic drugs cause cognitive decline.

The second trial, involving 700 older adults, will examine whether an app that educates seniors about potential harms associated with anticholinergic medications and assigns a personalized risk score for dementia induces people to initiate conversations with physicians about getting off these drugs.

Moving patients off anticholinergic drugs requires “slow tapering down of medications” over three to six months, at a minimum, according to Nagham Ailabouni, a geriatric pharmacist at the University of Washington School of Pharmacy. In most cases, good treatment alternatives are available.

Advice for Older Adults

Seniors concerned about taking anticholinergic drugs “need to approach their primary care physician and talk about the risks versus the benefits of taking these medications,” said Shellina Scheiner, an assistant professor and clinical geriatric pharmacist at the University of Minnesota.

Don’t try stopping cold turkey or on your own. “People can become dependent on these drugs and experience withdrawal side effects such as agitation, dizziness, confusion and jitteriness,” Ailabouni said. “This can be managed, but you need to work with a medical provider.”

Also, “don’t make the assumption that if [a] drug is available over the counter that it’s automatically safe for your brain,” Boustani said. In general, he advises older adults to ask physicians about how all the medications they’re taking could affect their brain.

Finally, doctors should “not give anticholinergic medications to people with any type of dementia,” DeKosky said. “This will not only interfere with their memory but is likely to make them confused and interfere with their functioning.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

The Consequences of Untreated Pain

By Roger Chriss, Columnist

Pain is an alarm signal requiring attention. Whether the pain lasts minutes or months, it demands a response. To ignore pain is to invite serious consequences, from burned skin or an infected wound to a damaged joint or dysfunctional nerve. It is for this reason that healthcare professionals ask patients where it hurts.

Recent research found the consequences of untreated pain go farther and deeper than are generally recognized:

• JAMA Internal Medicine reported that older people with chronic pain experience faster declines in memory and are more likely to develop dementia.
• Pain Medicine reported that osteoarthritis and related joint pain were strongly associated with memory loss.
• Arthritis Care & Research reported that pain severe enough to interfere with daily life was associated with an increased risk of mortality.

In the latter study, people who were “often troubled with pain” had a 29% increased risk of dying, and those who reported “quite a bit” or “extreme’ pain” had 38% and 88% increased risk of mortality, according to Medical Dialogues.

These results are new, but they are far from unique. For years researchers have been finding that chronic pain conditions have major long-term medical consequences.

In 2011, Pain Medicine reported that chronic pain “negatively impacts multiple aspects of patient health, including sleep, cognitive processes and brain function, mood/mental health, cardiovascular health, sexual function, and overall quality of life.”

In 2016, a study in the Journal of Pain Research reviewed the research literature and found that chronic pain “has significant consequences for patients, as well as for their families, and their social and professional environment, causing deterioration in the quality of life of patients and those close to them.”

However, awareness of the consequences of persistent pain conditions does not necessarily translate to effective care. As I wrote in a recent column, under treatment of pain is common, and the CDC opioid prescribing guidelines and groups like Physicians for Responsible Opioid Prescribing (PROP) are making things worse by demonizing opioids.

“The role of opioid analgesics has been distorted to the point where the word ‘oxycodone’ uttered in front of a patient in my palliative medicine clinic is met with raised eyebrows,” wrote Susan Glod, MD, in a recent op/ed on “The Other Victims of the Opioid Epidemic” published in The New England Journal of Medicine

Fear of a drug makes for bad medicine. Although opioid therapy includes possible cognitive side effects, so do anticholinergic muscle relaxants, which have been shown to increase the risk of dementia. Similar risks exist for many other treatment modalities.

Thus, effective management of chronic pain conditions requires expert care. The best results are often obtained in pain management programs that combine drug therapy with physical therapy or other modalities tailored to the individual patient’s needs.

Persistent pain is a danger sign that a major and potentially life-threatening toll is being exacted on the human body and mind. We do not have the luxury of ignoring or undertreating chronic pain conditions. Good pain management is one of the best ways to improve long-term outcomes and quality of life.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society.

Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Chronic Pain Raises Risk of Dementia

By Pat Anson, Editor

Chronic pain has long been associated with a variety of health problems, including depression, anxiety, insomnia, high blood pressure and an impaired immune system. Now there’s something else to worry about.

A large new study by researchers at UC San Francisco has found that older people with chronic pain experience faster declines in memory and are more likely to develop dementia, an indication that chronic pain could cause changes in the brain. The study, published in JAMA Internal Medicine, appears to be the first to make this association.

UCSF researchers analyzed data from over 10,000 participants aged 60 and over who were enrolled an ongoing national study of older Americans. Patients were surveyed about their pain and cognition in 1998 and 2000.

Those who said they were persistently troubled by moderate or severe pain declined 9.2 percent faster in tests of their memory and cognitive ability over the next 10 years than those who said they were not troubled by pain.

The patients who complained about persistent pain also had a 7.7 percent greater chance of developing dementia.

“A persistent report of moderate to severe pain, which may reflect chronic pain, is associated with accelerated cognitive decline and increased dementia probability in a large population-representative data set of elders,” wrote first author Elizabeth Whitlock, MD, a postdoctoral fellow in the UCSF Department of Anesthesia and Perioperative Care.

“Clinicians should be aware of this association, which persisted after extensive statistical adjustment for confounding health and demographic factors. Patients reporting ongoing pain may be at higher risk for current and incident cognitive impairment and physical debility.”

Whitlock says the additional loss of memory in participants who reported persistent pain suggests that they will have a harder time with daily living tasks, such as managing their medications and finances.

"Elderly people need to maintain their cognition to stay independent," she said. "Up to one in three older people suffer from chronic pain, so understanding the relationship between pain and cognitive decline is an important first step toward finding ways to help this population."

The data that the researchers analyzed did not include information about opioid use, so researchers could not tell which of their participants were taking opioid painkillers. While opioid use could be the cause of the cognitive changes, so could the pain itself. For example, a recent study of chronic pain sufferers found that those who took non-steroidal anti-inflammatory drugs (NSAIDs) had nearly the same increased dementia risk as those taking opioids.

"This means we have to consider the potential direct effects of chronic pain on cognition," Whitlock said.

People who suffer from chronic pain tend to have diminished attention and impaired memory, and Whitlock says when pain is severe it could divert enough attention to interfere with the consolidation of memory. Another possibility is that the emotional stress of being in pain activates stress-hormone pathways in the body that have been implicated in cognitive decline. If either is the case, she said, then effectively treating the pain could protect cognition.

"This is something I really feel we can do something about as clinicians," Whitlock said. "It's part of taking care of the whole patient."

Benzos May Increase Dementia Risk

By Pat Anson, Editor

Anti-anxiety drugs often prescribed to chronic pain patients increase the risk of dementia and Alzheimer's disease when used long term, according to clinicians with the American College of Osteopathic Neurologists and Psychiatrists.

Benzodiazepines --  also known as benzos -- include brand name prescription drugs such as Valium, Ativan, Klonopin and Xanax. They were approved by the U.S. Food and Drug Administration to treat psychiatric conditions, but are also prescribed "off label" to treat bipolar disorder, insomnia, post traumatic stress disorder, and chronic pain.

A Canadian study of 9,000 patients found those who had taken a benzodiazepine for three months or less had about the same dementia risk as those who had never taken one.

But taking benzos for three to six months raised the risk of developing Alzheimer's by 32 percent, and taking them for more than six months boosted the risk by 84 percent.

Similar results were found by French researchers studying more than 1,000 elderly patients.

"Current research is extremely clear and physicians need to partner with their patients to move them into therapies, like anti-depressants, that are proven to be safer and more effective," saidHelene Alphonso, DO, Director of Osteopathic Medical Education at North Texas University Health Science Center in Fort Worth.

The case for limiting the use of benzodiazepines is particularly strong for patients 65 and older, who are more susceptible to falls, injuries, accidental overdose and death when taking the drugs. The American Geriatric Society in 2012 labeled the drugs "inappropriate" for treating insomnia, agitation or delirium because of those risks.

"It's imperative to transition older patients because we're seeing a very strong correlation between use of benzodiazepines and development of Alzheimer's disease and other dementias. While correlation certainly isn't causation, there's ample reason to avoid this class of drugs as a first-line therapy," said Alphonso.

In its draft guidelines for the prescribing of opioid pain medication, the Centers for Disease Control and Prevention (CDC) recommends that opioids and benzodiazepines not be prescribed concurrently whenever possible. A CDC study found that about 80% of unintentional overdose deaths associated with opioids also involved benzodiazepines. Nearly 6,500 people died from overdoses involving benzodiazepines in 2010.

Opioids, benzodiazepines and muscle relaxants are all central nervous system depressants. Mixing the drugs is potentially dangerous because their interaction can slow breathing and raise the risk of an overdose death.

In a study of over 35,000 patient visits for acute and chronic pain, recently published in the journal Pharmacoepidemiology and Drug Safety,  researchers found that the prescribing of benzodiazepines was three to four times more likely when opioids were also prescribed.

Over a third of the patients prescribed opioids for chronic musculoskeletal pain were given a sedative. And patients with a history of psychiatric and substance abuse disorders were even more likely to be co-prescribed opioids and sedatives.

"Multi drug use is the trailing edge of the opioid epidemic," said Mark Sullivan, MD, a professor of psychiatry and behavioral sciences at the University of Washington School of Medicine. "We are making progress on decreasing opioid prescribing, but co-prescribing of opioids and sedatives has not decreased.

"Patients who are on long-term combined opioid and benzodiazepine therapy are often on a treadmill. They feel relief when they take their medications and withdrawal when they stop, so they continue this combined therapy, even though many function poorly and some will die as a result."

Over 50,000 visits to emergency rooms in 2011 involved a combination of benzodiazepines and opioids, according to the Substance Abuse and Mental Health Services Administration (SAMHSA)