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.

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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.

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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.

Why a Bad Night’s Sleep Causes More Pain

By Pat Anson, PNN Editor

It’s no secret that chronic pain makes sleeping difficult. And lack of sleep often makes pain worse.  But how exactly does poor sleep cause more pain?

For the first time, scientists at the University of California, Berkeley, have identified neural glitches in the sleep-deprived brain that can intensify and prolong pain. Their findings, published in the Journal of Neuroscience, help explain the self-perpetuating cycles that contribute to pain and sleep loss.

“Anyone who has had persistent back pain knows that they don’t sleep well when they are in pain. They also know that when they don’t sleep well, it hurts more the next day,” said senior author Matthew Walker, PhD, a UC Berkeley professor of neuroscience and psychology.

"If poor sleep intensifies our sensitivity to pain, as this study demonstrates, then sleep must be placed much closer to the center of patient care, especially in hospital wards.”

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In a small study involving 25 healthy young adults, Walker and his colleagues found that nerves that process pain signals and activate the body’s pain relief hormones are disrupted by insufficient sleep. Study participants were given MRI brain scans twice – once after a good night’s sleep and once after a night of no sleep – and then subjected to a thermal pain test in the laboratory  

“We found some surprising changes. The sleep-deprived brain seems to let more pain in,” Walker said.

Brain imaging showed increased activity in the brain's somatosensory cortex, but there was less activity in the nucleus accumbens, a region of the brain's reward circuitry that increases dopamine levels. Dopamine is a neurotransmitter that’s been called the “feel-good hormone” because it is associated with feelings of euphoria and happiness.

Another key brain region found to slow down in the sleep-deprived brain was the insula, which evaluates pain signals and prepares the body to respond.

"This is a critical neural system that assesses and categorizes the pain signals and allows the body's own natural painkillers to come to the rescue," said Adam Krause, lead author of the study and a doctoral student in Walker's Center for Human Sleep Science lab at UC Berkeley.

To further test the sleep-pain connection, researchers surveyed more than 230 adults of all ages nationwide. Respondents were asked to report their nightly hours of sleep, as well as their day-to-day pain levels. The results showed that even minor shifts in sleep patterns were correlated with changes in pain sensitivity.

"The results clearly show that even very subtle changes in nightly sleep -- reductions that many of us think little of in terms of consequences -- have a clear impact on your next-day pain burden," Krause said.

"The optimistic takeaway here is that sleep is a natural analgesic that can help manage and lower pain," said Walker. "Yet ironically, one environment where people are in the most pain is the worst place for sleep -- the noisy hospital ward."

Walker's goal is to work with hospitals to create more sleep-friendly patient facilities.

"Our findings suggest that patient care would be markedly improved, and hospital beds cleared sooner, if uninterrupted sleep were embraced as an integral component of healthcare management," he said.

Several previous studies have found that getting a good night’s sleep helps reduce sensitivity to pain. Researchers in Norway measured pain sensitivity in more than 10,000 adults and found a strong link between pain and insomnia.

Another study in Norway found that women who have trouble sleeping are at greater risk of developing fibromyalgia – although it’s not clear if there’s a cause and effect relationship between the two symptoms.

Painkillers Raise Risk of Obesity and Hypertension

By Pat Anson, Editor

Commonly prescribed painkillers such as opioids and gabapentinoids  -- a class of pain medication that includes Lyrica and Neurontin – significantly raise the risk of obesity and high blood pressure, according to a large new study published in PLOS ONE.

British researchers analyzed health data on over 133,000 people, comparing the Body Mass Index (BMI), waist circumference, blood pressure and sleeping habits of patients taking pain relievers to those who did not. The study is believed to be the largest to look at the effects of painkillers on overall health.

“In the last two decades there has been a significant increase in the number of people being prescribed both opioid and non-opioid medications to treat chronic pain,” said lead author Sophie Cassidy, PhD,  a research associate at the Institute of Cellular Medicine, Newcastle University. “We already know that opiates are dependency-forming but this study also found patients taking opiates have the worst health. Obesity rates are much higher and the patients reported sleeping poorly.”

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Those taking opioids were 95% more likely to be obese, 82% more like to have a “very high” waist circumference and 63% more likely to have hypertension compared to the control group.  

“There could be a number of possible mechanisms by which opioids might be associated with weight gain. Sedation might decrease physical activity and therefore reduce energy expenditure, those in our cohort taking opiates were less active, and those taking both opiates and other sedative drugs were the least active. Opioids have also been shown to alter taste perception with a craving for sugar and sweet foods described,” Cassidy wrote.

“These results add further weight to calls for these chronic pain medications to be prescribed for shorter periods.”

Patients who took gabapentinoids were also more likely to be obese, have a bigger waist and higher blood pressure compared to those not taking the drugs.

Gabapentinoids are commonly prescribed as alternatives to opioids to treat neuropathy, shingles and fibromyalgia, although many patients complain about side effects such as weight gain, depression and anxiety.

As PNN has reported, gabapentinoids are also coming under scrutiny because they are increasingly being abused. Lyrica (pregabalin) and Neurontin (gabapentin) are being reclassified as controlled “Class C” substances in the UK, following a spike in the number of deaths involving the medications.

Last week, the West Virginia Board of Pharmacy designated gabapentin as a “drug of concern,” after overdoses in the state involving gabapentin rose from 36 deaths in 2012 to 106 in 2016.  Ohio, Pennsylvania and Kentucky have also reported increases in fatal overdoses involving gabapentin.

Negative Thoughts About Sleep Make Pain Worse

By Pat Anson, Editor

Negative thoughts about pain and not being able to sleep can worsen chronic pain conditions like fibromyalgia, arthritis and back pain, according to British researchers.

“Pain-related sleep beliefs appear to be an integral part of chronic pain patients' insomnia experience,” said Nicole Tang, a psychologist in the Sleep and Pain Laboratory at the University of Warwick. "Thoughts can have a direct and/or indirect impact on our emotion, behaviour and even physiology. The way how we think about sleep and its interaction with pain can influence the way how we cope with pain and manage sleeplessness.”

Tang and her colleagues developed a scale to measure beliefs about sleep and pain in chronic pain patients, along with the quality of their sleep.

The scale was tested on four groups of patients suffering from long-term pain and bad sleeping patterns, and found to be a reliable predictor of future pain and insomnia.

"This scale provides a useful clinical tool to assess and monitor treatment progress during these therapies," said Esther Afolalu, a graduate student and researcher at the University of Warwick. 

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"Current psychological treatments for chronic pain have mostly focused on pain management and a lesser emphasis on sleep but there is a recent interest in developing therapies to tackle both pain and sleep problems simultaneously."

Researchers found that people who believe they won't be able to sleep because of their pain are more likely to suffer from insomnia, thus causing more pain. The vicious cycle of pain and sleeping problems was significantly reduced after patients received instructions in cognitive-behavioural therapy (CBT), a form of psychotherapy in which a therapist works with a patient to reduce unhelpful thinking and behavior.

The study, published in the Journal of Clinical Sleep Medicine, is not the first to explore the connection between pain and poor sleep.

A 2015 study published in the journal PAIN linked insomnia and impaired sleep to reduced pain tolerance in a large sample of over 10,000 adults in Norway. Those who had trouble sleeping at least once a week had a 52% lower pain tolerance, while those who reported insomnia once a month had a 24% lower tolerance for pain.

Therapy Helps Chronic Pain Sufferers Sleep

By Pat Anson, Editor

British researchers say cognitive behavioral therapy can effectively treat insomnia in chronic pain patients – reducing their pain, fatigue and depression. But the therapy works best when delivered in person.

Cognitive behavioral therapy (CBT) is a form of psychotherapy, in which a therapist works with a patient to reduce unhelpful thinking and behavior. Poor sleep habits and insomnia have long been known to aggravate chronic pain conditions.

Researchers at the University of Warwick analyzed 72 studies involving over 1,000 patients who suffered from insomnia and chronic pain, and found that CBT was “moderately or strongly effective” in treating insomnia. The study has been published in the journal Sleep.

"This study is particularly important because the use of drugs to treat insomnia is not recommended over a long period of time, therefore the condition needs to be addressed using a non-pharmacological treatment,” said lead researcher Dr. Nicole Tang of the University of Warwick’s Department of Psychology.

"Poor sleep is a potential cause of ill health and previous studies suggest it can lead to obesity, diabetes, stroke, coronary heart disease - even death. Insomnia can also increase the risk of depression, anxiety and substance misuse. It is also a major problem for those suffering pain that lasts longer than three to six months and that is why we looked at this group.”

The most popular CBT strategies included education about good sleeping habits, such as a regular sleeping patterns and avoiding stimulus before going to bed.

Researchers found there was a mild to moderate decrease in pain immediately after therapy, as well as a decrease in depression. But CBT was not as effective when delivered electronically - either over the phone or via the Internet.

"We found little evidence that using therapies delivered either by phone or computer benefitted insomniacs. The jury is still out on the effectiveness of using automated sleep treatments. We found that, at the moment at least, delivering therapies personally had the most positive effect on sleeplessness," said Tang.

Several previous studies have found that getting a good night’s sleep helps reduce sensitivity to pain.

Researchers in Norway measured pain sensitivity in more than 10,000 adults and found a strong link between pain and insomnia. Patients with severe insomnia and chronic pain were twice as likely to pull their hands out of cold water early – a standard test to measure pain – than people who had neither condition.

A small 2012 study at Wayne State University found that people who had 10 hours of sleep a night had less sensitivity to pain in a heat test.

Miss Understood: A Taste of Remission

By: Arlene Grau, Columnist

If you ask me to plan something, almost anything that requires me being somewhere on a certain day for any amount of time, I would have to decline because I never know how I'll be feeling on any given day.

Now ask me to plan a family vacation that would take me to Hawaii, where I would be 5 hours away from my doctor by plane – well, that would be insane.

However, I did just that and the results were better than expected.

I had my Rituxan infusion a month prior to leaving in hopes that it would kick in just before I left. My body, however, had a different agenda. I began feeling ill the week after my treatment. On top of that, I suffered a bad fall at home. I sprained my ankle, bruised my hip, and hurt my knee.

Instead of making progress, I was taking several steps backwards. I had tried to prepare my body for months and it was beginning to feel like it was all in vain.

But my husband and doctor didn't allow me to give up. My doctor prepared an emergency plan for me before I left. He prescribed backup antibiotics in case I became ill, started me on a temporary prednisone dosage, printed up my most recent patient summary (since I was taking so many medications with me), and gave me contact information for a rheumatologist in Hawaii in the event that I needed to be seen. He even called the other doctor ahead of time and told me to email him for anything.

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Although my body wasn't completely ready, I felt like I had the tools necessary to handle any medical emergency I may have.

Now, I don't know if it was the simple fact that I removed myself from all the stressors in my life, but I felt so much better while I was in Hawaii during that one week than I have since I was first diagnosed with rheumatoid arthritis eight years ago.

My theory is that the change in climate helped with the inflammation I was suffering from. I know that when it's very cold and dry, I tend to flare up and feel very ill. And when it's really hot and the sun is pounding down on me, I feel my weakest and just as sick.

But out there I was met with humidity and sunlight that didn't feel like it was stripping away every ounce of energy I had.

I had one or two trying days; granted I was doing a lot more than I've ever done at home as far as activities and walking go. But I was extremely proud of everything I was participating in. I even got to enjoy my 30th birthday in Hawaii, one I never thought I would live to see.

I knew as soon as we got home that something was different because I woke up feeling like I had been hit by a truck. As quickly as the swelling and inflammation left, it returned. My insomnia is back and my migraines are more intense.

But I got taste of what remission might be like.

It was a great vacation with a bittersweet ending because, instead of dreaming about the visual paradise I was in, I'm left day dreaming about the physical paradise I felt -- the one that had less limitations and more of my old self.

Arlene Grau lives in southern California. She suffers from rheumatoid arthritis, fibromyalgia, lupus, migraine, vasculitis, and Sjogren’s disease.

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

Chronic Fatigue Patients ‘Disrespected and Rejected’

By Pat Anson, Editor

An independent panel convened by the National Institutes of Health is calling for major changes in the way the healthcare system treats people suffering from chronic fatigue – a complex and poorly understood disorder that affects an estimated one million Americans, most of them women.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by extreme fatigue, chronic pain, impaired memory, insomnia, and other symptoms that do not improve with rest.  Many of the symptoms overlap with other diseases and disorders -- including fibromyalgia, depression, and inflammation – making a correct diagnosis even more difficult.

There is also a stigma often associated with chronic fatigue.

“Both society and the medical profession have contributed to ME/CFS patients feeling disrespected and rejected. They are often treated with skepticism, uncertainty, and apprehension and labeled as deconditioned or having a primary psychological disorder,” the panel states in its final report.

“ME/CFS patients often make extraordinary efforts at extreme personal and physical costs to find a physician who will correctly diagnose and treat their symptoms while others are treated inappropriately causing additional harm.”

Although the economic burden of chronic fatigue is estimated at between $2 billion and $7 billion annually, the panel said there has been “minimal progress” in improving the state of science for ME/CFS over the last 20 years. There are no pathogens linked to chronic fatigue, no diagnostic tests and no known cures.

"We need to learn more about the cellular and molecular mechanisms of this disease and how immunologic, neurologic, and other factors contribute to ME/CFS," said Carmen Green, MD, the panel’s chair and professor of anesthesiology, obstetrics and gynecology, and health management and policy at the University of Michigan Schools of Medicine and Public Health.

"We need to fund more studies that can be easily reproduced, and we must gain a better understanding of how ME/CFS affects people and their families in terms that are clinically meaningful to them. In addition, we need to have a greater understanding of the impact of ME/CFS across the life span, especially in underserved and vulnerable populations."

What little research that has been done has focused on Caucasian, middle-aged women.  The panel said new studies need to include children, minorities, men, patients living in rural areas, and those who are homebound.

To address these knowledge gaps, the panel is calling for more research and opportunities for new investigators to study ME/CFS. It also called for the creation of a repository of biological samples from chronic fatigue patients (e.g., serum, whole blood, RNA, DNA) to support new studies.

In addition, the panel recommended new educational training courses to help health care providers diagnose and treat ME/CFS.

"ME/CFS exists, and despite the absence of a clear definition, an estimated one million Americans are affected by it," said Green. "In order to develop primary prevention strategies and effective drug treatments, there needs to be a clear understanding of its causes and the populations it affects."

Much of the information gathered by the panel came during a public workshop and public comment period in December of last year. The five member panel, which included Penney Cowan of the American Chronic Pain Association, operated as an independent commission. Its final report is not a policy statement of the NIH or the federal government, and there are no guarantees its recommendations will be funded or acted upon.