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Saturday, October 5, 2019

Pupils May Help Identify Alzheimer’s Decades Before Symptoms Appear

There’s an old saying that the eyes are the window to the soul. While that very well may be the case, a new study finds that they may also be a window to the mind and an accurate predictor of the onset of Alzheimer’s disease long before actual symptoms begin to appear.
Researchers from the University of California, San Diego, say that measuring how quickly and drastically a person’s pupil dilates while solving a problem or thinking critically may serve as an accurate, low-cost, and low-invasive way to screen for Alzheimer’s decades before any symptoms appear.
Alzheimer’s disease, a devastating condition that results in cognitive deterioration and memory loss, only reveals itself late in life. However, the condition actually begins taking root and damaging the brain many years before symptoms appear. With this in mind, early detection is key to slowing the disease’s progression. If the research team’s findings about pupil behavior are accurate and reliable, it would represent a major breakthrough in the early detection and treatment of Alzheimer’s among genetically at risk patients all over the world.
Up until now, the majority of researchers studying the early onset and progression of Alzheimer’s have focused on two areas: the build up of a certain type of protein plaques, amyloid-beta, in the brain, and the entanglement of another protein, called tau, in the brain. Both of these proteins have been shown to slowly damage and kill neurons, resulting in a slowly-but-surely progression into cognitive dysfunction, and ultimately Alzheimer’s.
For this study, the research team focused on pupil responses in the eye. Pupillary responses are controlled by a cluster of neurons in the brain stem called the locus coeruleus (LC). Besides just controlling pupil adjustments, the LC also helps regulate arousal and modulate cognitive function. Tau, one of the aforementioned proteins directly linked to cognitive decline, and Alzheimer’s earliest known biomarker, first develops within the LC.
Besides just changing pupil sizes in response to light and other stimulants, the LC also drives pupillary responses (changes in diameter) during cognitive tasks or critical thinking. Generally speaking, pupils get bigger the more difficult the task or question. So, researchers theorized that a buildup of tau in the LC may also influence pupil behavior during a cognitive task.
Furthermore, prior research has already suggested that adults with mild cognitive impairment, often an accurate indicator of Alzheimer’s development later on in life, exhibited greater pupil dilation and cognitive effort while performing a task compared to cognitively normal individuals. This was true even when both groups produced generally the same results in reference to the task.
For their experiment, the research team theorized that middle aged, cognitively normal individuals with a genetic predisposition for Alzheimer’s would also display greater, and faster, pupil dilation during a cognitive task. After performing an experiment with 1,119 men between the ages of 56-66, the researchers’ theory was confirmed: cognitively normal participants who showed no sign of Alzheimer’s besides a genetic susceptibility to the disease, were associated with greater pupil dilation and greater cognitive effort over all.
“Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” explains Dr. William S. Kremen, the study’s first author, in a release.
The study is published in the Neurobiology of Aging.
https://www.studyfinds.org/window-to-the-mind-pupils-may-help-identify-alzheimers-decades-before-symptoms-appear/

Generation Rx: Children Being Prescribed Off-Label Meds At Increasing Rates

American children are already being prescribed various types of medications at exceedingly high rates to begin with, but a new study conducted at Rutgers University finds that the frequency of off-label medication orders for children is on the rise as well.
“Off-label” refers to a medication being used to address a different condition than it was approved to treat by the FDA. An example of an off-label med prescription for a child would be a doctor recommending anti-depressant medication for ADHD symptoms.
The research team were alarmed by their findings, and believe this study illustrates a glaring need for improved oversight and regulation when it comes to ensuring that children are prescribed safe, and effective, medication.
Data collected between 2006-2015 by the CDC and Prevention’s National Ambulatory Medical Care Surveys was analyzed for the study. More specifically, researchers looked at information on doctor’s office visits all over the United States, and investigated the frequency, trends, and reasons why doctors prescribed off-label meds for individuals under the age of 18.
In many ways, this study is incredibly overdue — it is the first in a decade to look at trends among non-hospital doctors prescribing off-label medicine to children. Researchers focused specifically on systemic drugs, or drugs that work throughout the body but also carry a greater chance of toxicity.
According to researchers, many of the off-label drugs being prescribed to children by doctors all over the country haven’t even been properly tested among adolescent populations.
“Off-label medications – meaning medications used in a manner not specified in the FDA’s approved packaging label – are legal. We found that they are common and increasing in children rather than decreasing,” comments senior author Daniel Horton, assistant professor of pediatrics and a pediatric rheumatologist at Rutgers Robert Wood Johnson Medical School, in a release. “However, we don’t always understand how off-label medications will affect children, who don’t always respond to medications as adults do. They may not respond as desired to these drugs and could experience harmful effects.”
The research team studied an estimated two billion adolescent visits to a physician, and found that in about 19% of those visits the doctor ordered one or more off-label systemic drugs. Most of the time, these drugs were intended to treat a common problem, such as asthma or a respiratory infection. Among visits that resulted in at least one prescription, off-label drugs were ordered in 83% of newborn visits, 49% of infant visits, and about 40% of visits among other adolescent ages.
The study also noted that prescription of off-label meds has increased over time; among visits that resulted in at least one prescription, off-label rates increased from 42% in 2005 to 47% by 2015.
Interestingly, girls and children with chronic conditions seemed to be prescribed off-label meds more often than other patients. Furthermore, doctors practicing medicine in southern U.S. states exhibited higher instances of off-label drug orders than doctors from other areas of the country. Doctors focusing on a specific medical field, commonly referred to as specialists, also ordered off-label meds more often than general practitioners.
The most common off-label drugs prescribed by doctors included antihistamines for respiratory infections, anti-depressants for ADHD, and numerous types of antibiotics for respiratory infections.
“Despite the laws in this country and Europe that encourage and require research on medications for children, we found that physicians are increasingly ordering certain medications off-label for children,” Horton says. “Use of some off-label drugs is supported by high-quality evidence. For example, drugs approved to prevent vomiting caused by chemotherapy also work quite well in treating more common causes of vomiting in children, such as from viruses. We need this kind of evidence to determine the appropriateness of use of many other drugs currently used off-label to treat a wide range of conditions in children.”
The study is published in the scientific journal Pediatrics.
https://www.studyfinds.org/generation-rx-u-s-children-being-prescribed-off-label-meds-at-increasing-rates-study-finds/

Flu Season Alert: Hand Sanitizer Not Very Effective Against Virus Strain

Got four minutes? That’s how long researchers say it will take for a person to rub their hands together with sanitizer before Influenza-A is deactivated.

Flu season is fast approaching, which means millions will be using hand sanitizer more often in an effort to protect themselves from a flu infection. Most people, including medical professionals, believe that flu viruses are quickly neutralized after coming into contact with an ethanol-based sanitizer, but a new study finds that isn’t the case for at least one flu strain.
Researchers from Kyoto Profectural University of Medicine in Japan have discovered that the influenza A virus (IAV) remains active and infectious within infected wet mucus even after being exposed to an ethanol-based sanitizer — for two full minutes. According to their research, it took nearly four minutes of exposure to a sanitizer to completely deactivate the virus.
Needless to say, most people aren’t rubbing their hands together with sanitizer for four minutes.
The influenza A virus is able to survive so stubbornly thanks to the think consistency of sputum, a mixture of mucus and saliva commonly coughed up by flu patients, produced in infected individuals. The thick texture of the sputum impedes the ethanol in the sanitizer from reaching and neutralizing the influenza A virus.
So, imagine someone with the influenza A virus coughs on their hand and then shakes yours a few minutes later. You would have to rub your hands together with sanitizer for four minutes to deactivate the virus if even the slightest trace of wet, infected mucus were to make its way on to your hand.
“The physical properties of mucus protect the virus from inactivation,” says physician and molecular gastroenterologist Dr. Ryohei Hirose in a release by the American Society for Microbiology. “Until the mucus has completely dried, infectious IAV can remain on the hands and fingers, even after appropriate antiseptic hand rubbing.”
According to the study, a small splash of sanitizer quickly rubbed together for a few seconds just isn’t going to cut it against this particular flu virus. The research team say that doctors and other medical professionals should be especially careful; if they don’t properly deactivate the virus between seeing various patients they could quickly spread the flu to multiple people.
First, the study’s authors analyzed the physical properties of mucus, and just as they expected, they noted that ethanol had a much harder time moving through mucus than it does through saline. Next, sputum collected from IAV patients was dabbed on human fingers and analyzed. The researchers goal during this phase was to try and simulate a situation in which medical personnel transmit the virus as best they could.
After being exposed to an ethanol hand sanitizer for two minutes, the IAV virus was still active within the mucus on the fingertips. After four minutes, the virus was completely deactivated.
This study is especially noteworthy because it challenges previous research that had found ethanol to be effective against IAV. Dr. Hirose, however, believes he knows why his study came to such different conclusions: prior research had analyzed mucus that was already dry, while this study analyzed mucus that was still wet. In fact, when Dr. Hirose and his team repeated their experiment using dry mucus, the virus was completely deactivated by the sanitizer within 30 seconds.
It’s also worth noting that the fingertip test used for this study may not exactly mimic typical hand rubbing motions, which may be a bit more effective at spreading hand sanitizer throughout the hand.
Right now, both the Centers for Disease Control and Prevention and the World Health Organization officially recommend using sanitizer regularly for 15-30 seconds to ensure optimal hand hygiene. Unfortunately, that just isn’t enough rubbing to stop IAV, according to Dr. Hirose.
On the bright side, researchers did identify a hand-cleaning strategy that is even more effective than sanitizers. Washing hands together with antibiotic soap was shown to deactivate the IAV virus within 30 seconds, even when mucus was still wet.
The study is published in the scientific journal mSphere.
https://www.studyfinds.org/flu-season-alert-hand-sanitizer-not-very-effective-against-virus-strain/

Study suggests inaccuracies in physicians’ electronic documentation

  • A new study in JAMA Network Open found inconsistencies between the way emergency department residents documented patient encounters in an EHR and what trained observers witnessed.
  • In the study, 12 observers (including two physicians and 10 undergraduate students with an interest in medicine) shadowed nine physicians during 180 patient encounters in the emergency departments of two teaching hospitals, which weren’t identified. They focused their observations on two parts of each encounter: the review of systems, where physicians ask patients about their symptoms, and the physical exam. The encounters were recorded.
  • Residents documented a median of 14 systems (or organs in the body) as being discussed with patients during the review of systems portion of the encounter, while observers recorded a median of five systems, the ​study found. During the physical exams, physicians documented a median of eight systems examined per encounter, while observers noted a median of 5.5.
CMS has developed complicated rules and regulations about how to document a patient encounter to account for the severity and complexity of a patient case and the amount of time a physician spends working on it. But recognizing that the documentation rules may be burdensome and outdated, officials have said they are working on reforming the process.
Heavy documentation and charting workloads are a cause of provider burnout, which is a major concern to health systems, hospitals and medical groups because burnout can lead to worsening well-being for physicians and lower-quality patient care.
It’s also costly for the healthcare industry. For example, a recent study published in the Annals of Internal Medicine calculated annual burnout costs between $2.6 billion and $6.3 billion, including costs from staff turnover, lower productivity and other factors.
Burnout is not the only consequence of complicated documentation requirements.
The study’s authors note that CMS rules create unintended incentives for providers to maximize reimbursement from payers by documenting extensively.
This problem is compounded by a feature in some EHRs that allows providers to auto-populate required fields in the software when documenting, particularly for the review of systems and physical exam portions of a patient encounter, the study authors wrote. However, auto-populating can lead to inaccuracies if the data entered into the fields does not reflect the specific circumstances of a patient case.
Inaccurate documentation also increases the risk of patient safety issues, which can impact patient outcomes, providers’ quality scores, reputation and revenues under value-based reimbursement models. Faulty documentation also exposes facilities to the risk of payer audits.
In an accompanying editorial, commentators from the Icahn School of Medicine at Mount Sinai note that studies analyzing the accuracy of electronic documentation are rare but necessary. “An improved understanding of the root cause of discrepancies between patient report and physician documentation will be helpful in detecting ways to prevent them in the future,” they wrote.
https://www.healthcaredive.com/news/jama-study-suggests-inaccuracies-in-physicians-electronic-documentation/563154/

Sacklers reaped up to $13 billion from OxyContin maker, U.S. states say

OxyContin maker Purdue Pharma LP steered up to $13 billion in profits to the company’s controlling Sackler family, according to U.S. states opposing efforts to halt lawsuits alleging the company and its owners helped fuel the U.S. opioid epidemic.

The wealthy Sacklers received the money from Purdue during an unspecified time frame, according to court documents and portions of a deposition filed in the drugmaker’s bankruptcy proceedings this week.
Purdue ultimately transferred $12 billion or $13 billion to the family, a company adviser testified in the deposition. The deposition, taken last week, was revealed in court filings on Thursday and Friday.
The financial figure is significantly larger than the roughly $4 billion previous lawsuits have alleged the Sacklers took out of Purdue, and was cited as part of coordinated legal broadsides this week against the company’s attempts to shield itself and the family from sprawling opioid litigation.
Many states want the Sacklers to contribute more than an initial $3 billion they have pledged toward resolving the lawsuits as part of a settlement Purdue has proposed.
Attorneys general from 24 states and the District of Columbia on Friday objected to Purdue’s September request that a U.S. bankruptcy judge halt more than 2,600 lawsuits seeking billions of dollars in damages, and they raised financial transfers to the Sacklers in their legal arguments.
So, too, did lawyers representing 500 cities, counties and Native American tribes, according to an earlier court filing.
“The distribution numbers do not reflect the fact that many billions of dollars from that amount were paid in taxes and reinvested in businesses that will be sold as part of the proposed settlement,” said Daniel S. Connolly, a lawyer for family members facing lawsuits who are related to the late Raymond Sackler, one of the modern Purdue’s co-founders, in a statement.
A spokesman for relatives of another deceased company co-founder, Mortimer Sackler, who also face litigation, had no immediate comment.
Purdue had no immediate comment on the payments. The company and family have denied allegations they contributed to the U.S. opioid crisis.
The lawsuits, largely brought by state and local governments, allege Purdue and the Sacklers contributed to a public health crisis that has claimed the lives of nearly 400,000 people since 1999 by aggressively marketing opioids while downplaying their addiction and overdose risks.
“The Sacklers are billionaires, they are not bankrupt,” Massachusetts Attorney General Maura Healey, among the officials opposing Purdue’s efforts to halt lawsuits, told Reuters in an interview. “They should not be allowed to use the filing to shield their assets.”
Purdue filed for Chapter 11 bankruptcy protection last month after reaching a deal it valued at more than $10 billion that would resolve the bulk of the cases against the company and the Sacklers.
The company contends it needs the litigation against it and the Sacklers paused for about nine months so it can attempt to settle with hold-out plaintiffs and preserve money that would otherwise be spent fighting the cases.
Purdue said the costs of continued litigation were “staggering,” putting its legal expenses this year at nearly $250 million.
“Without a stay of the litigation, only lawyers will win,” the company said in a statement.
Typically, a bankruptcy filing triggers an “automatic stay” of all litigation without a specific order from a judge.
However, Purdue is seeking an injunction to stop the lawsuits because the Sacklers did not seek bankruptcy protection and there is an exception to the automatic stay for government actions that seek to enforce laws related to public health and safety.
Healey said the exception gives the states a strong argument to move forward with their cases against the OxyContin maker. “We’re exercising our police power and have the right to do so,” she said.
The Sacklers have offered to cede control of Purdue to the plaintiffs and contribute $3 billion, and potentially more through the sale of another pharmaceutical business they own, toward the proposed settlement. Purdue is also in discussions to resolve a U.S. Justice Department probe that could carry a financial penalty.
Healey said the Sacklers should increase their contribution and she criticized the structure of the deal, which is premised in part on the continued sale of OxyContin, a drug that critics say helped launch the nation’s opioid addiction crisis.

https://www.marketscreener.com/news/Sacklers-reaped-up-to-13-billion-from-OxyContin-maker-U-S-states-say–29336762/

Social Security Debate Shifts From Benefit Cuts to Bigger Checks

The Social Security debate has moved left.
That shift, evidenced by presidential candidates’ plans and a bill backed by nearly 90% of House Democrats, departs from years of conversations about an elusive bipartisan compromise where Democrats agree to lower promised benefits and Republicans accept higher taxes.
Instead, President Trump has ruled out cuts to future benefits. Democrats have lined up behind larger benefits and higher taxes.
Democrats’ proposals show a party growing more comfortable with tax increases and shifting away from trying to reduce budget deficits. They have been nudged by activists trying to reset Social Security discussions dormant in Congress since the failure of President George W. Bush’s partial privatization plan.
Now, Democrats want to expand the popular program, emphasizing low-income retirees, widows and people who left the workforce to care for family members.
“Whatever we do is going to be bold,” said Rep. Dan Kildee (D., Mich.).
President Trump’s no-benefit-cuts position in 2016 shrank the partisan divide, tempering the Democrats’ advantage on the issue. Positions taken since then by House Democrats and candidates Elizabeth Warren, Bernie Sanders and Joe Biden widen that gap again.
“It’s an interesting story of how a policy position, whether I agree with it or not, can go from being a fringe position to a dominant position of a political party in a relatively short period of time,” said Andrew Biggs, resident scholar at the conservative American Enterprise Institute.
Unlike other safety-net programs such as food stamps, Social Security is viewed as an earned benefit, because it is largely funded through payroll taxes and check sizes are calculated based on earnings. It enjoys unique support across age groups and political affiliations.
In a 2018 Pew Research Center poll, 78% of Democrats and 68% of Republicans opposed cuts in future benefits. Younger voters showed more support for reducing future benefits, and 42% of people ages 18 to 29 assume they won’t get any benefits.
Social Security presents a political challenge, but it is also a math problem. Today’s taxes must generate enough money to pay benefits that today’s recipients accrued over their working lives. That math is changing. The demographic bulge of baby boomers is retiring, and living longer. Because high-income workers have experienced faster wage growth than the rest of the population, a greater share of U.S. wages is now exempt from the payroll tax, which stops at $132,900. That smaller tax base contributes to the long-run shortfalls.
Costs are projected to exceed income next year for the first time since 1982, forcing the program to dip into its nearly $3 trillion trust fund, built up when payroll taxes exceeded benefits.
Unless Congress acts, that trust fund will be depleted in 2034 and benefits would be automatically cut by more than 20%. Congress could fill the gap by raising payroll taxes or diverting general-fund revenue. Less disruptive changes now could close the shortfall, but lawmakers have little incentive to move.
Make benefits richer, and the trust fund runs out sooner. Raise taxes, increase the retirement age or slow benefit increases, and the program stays solvent longer.
Ms. Warren would increase everyone’s benefits by $200 a month, paid for in part by taxing investment income. Mr. Biden would give a bonus to the oldest Americans, and raise payments to surviving spouses. Mr. Sanders would tax wages above $250,000 to extend the program’s solvency and raise minimum benefits.
That is all far from where Democrats were earlier this decade, when both parties focused on deficit reduction. As part of a deal, President Obama proposed a formula under which Social Security benefits would grow more slowly.
By late 2016, however, Mr. Obama embraced more generous benefits, and presidential candidate Hillary Clinton backed expansion. Mainstream Democrats joined progressives like former Sen. Tom Harkin of Iowa in support of boosting benefits.
“Now, we’re seeing some variations on a theme,” said Nancy Altman, president of Social Security Works, an advocacy group. “It becomes a clear distinction between the parties.”
A plan from Rep. John Larson (D., Conn.) would expand benefits, raise payroll taxes and lower income taxes on benefits.
Mr. Larson’s Social Security 2100 Act would gradually bump the tax rate from 6.2% each on employers and employees to 7.4% each by 2043. That would hit every worker, including low-income ones. Social Security’s progressive benefit structure counteracts that regressive tax.
Mr. Larson would also impose payroll taxes on wages above $400,000, leaving an exemption for wages between $132,900 and $400,000. Eventually, inflation would erase that gap and all wages would face Social Security taxes.
His plan would extend Social Security’s solvency for at least 75 years, according to the chief actuary of the Social Security Administration. But the Congressional Budget Office, using different methodology, says solvency would last only through 2041.
Mr. Larson wants a House vote soon, though his bill stands little chance of becoming law with Republicans running the White House and Senate. He said the way the 2008 financial crisis sapped private retirement savings underscored the importance of Social Security’s guarantee and helped drive Democrats toward benefit expansion. Nearly 90% of House Democrats, 209, have signed on to the bill.
“This is a bipartisan issue across the country,” he said. “Not a bipartisan issue in Congress. But I think once people have to vote on it, it might become more bipartisan than people imagined.”
Republicans call the Democratic proposals nonstarters, but they haven’t coalesced around anything.
Some GOP lawmakers say they are open to a combination of revenue and spending changes and emphasize bipartisanship — as in 1983, when President Reagan and congressional Democrats raised the retirement age and accelerated scheduled tax increases.
Legislatively, that is likely required for any plan to become law. The fast-track, simple-majority procedure used for the 2017 tax cut and 2010 health law doesn’t apply to Social Security. One party would either need to get 60 votes or scrap the Senate filibuster.
“Democrats want to raise the payroll tax. Republicans aren’t wild about that, but it’ll be a compromise,” said Sen. Rob Portman (R., Ohio). “It has to happen soon to avoid the train wreck, so the sooner the better.”
But Mr. Trump vowed in 2016 to preserve promised Social Security benefits, helping himself politically but putting him at odds with many GOP lawmakers. Also, Republicans now rely more on older voters, making them more reluctant to reduce future benefits.
“It leads to them abandoning their prior policies on Social Security, but not knowing what their future policies are,” Mr. Biggs of the American Enterprise Institute said.
Nonpartisan groups still produce proposals along the old-compromise lines. Recently, the Concord Coalition and the Committee for a Responsible Federal Budget offered one designed to boost economic growth. It would encourage older workers to delay retirement and provide a “poverty protection benefit” for low-income workers.
But in Congress, there is little urgency or appetite for compromise proposals. Social Security may stumble toward insolvency in 2034 — sooner if there is a recession or later in a booming economy.
Rep. Tom Reed (R., N.Y.), the top Republican on the Social Security subcommittee, said some benefit increases might be worth examining. He opposes across-the-board increases or adding investment-income taxes.
“The longer we wait, we have fewer and fewer solutions that can be implemented in a practical way,” he said. “[I] would love to do this without tax increases or revenue increases, but it is clear if you do the math that is becoming more and more difficult.”
https://www.marketscreener.com/news/Social-Security-Debate-Shifts-From-Benefit-Cuts-to-Bigger-Checks–29340331/

Friday, October 4, 2019

Can Anti-TNF Meds for Inflammatory Diseases Reduce Alzheimer’s Risk?

Systemic inflammatory diseases involving tumor necrosis factor (TNF) increased the risk of Alzheimer’s disease, but that risk was reduced in patients who used anti-TNF biologics, an analysis of 56 million adults’ electronic health records showed.
While rheumatoid arthritis increased Alzheimer’s risk, it was reduced in patients taking etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade), according to Rong Xu, PhD, of Case Western University in Cleveland, and co-authors.
Similarly, people taking etanercept and adalimumab for psoriasis also had their risk of Alzheimer’s reduced, the researchers reported in a manuscript on the preprint server medRxiv.
These findings show the power of combining expert knowledge with big data analytics, Xu said. “Retrospective clinical studies using very large databases of patient electronic health records have high potential in uncovering risk associations among complex diseases and potential novel drug repurposing opportunities, as in this example where anti-TNF drugs might have a new use in Alzheimer’s disease and associated dementia,” she told MedPage Today.
The findings also reinforce the concept that late-onset Alzheimer’s may have multiple causes, added study author Mark Gurney, PhD, chief executive officer of Tetra Therapeutics in Grand Rapids, Michigan. “In this subset of patients, TNF produced in the body is an important risk factor for Alzheimer’s disease and is of the same magnitude as genetic risk factors such as APOE4,” Gurney told MedPage Today.
The analysis comes after years of speculation about how anti-inflammatory drugs might affect cognition. A phase II trial of etanercept in Alzheimer’s disease published in 2015 showed positive trends but no significant changes in cognition, behavior, or global function. Yet, observational data suggests there might be a link: a 2016 nested case-control study found that the relative risk of Alzheimer’s disease was lower in rheumatoid arthritis patients taking etanercept, and earlier this year, the Washington Post reported that Pfizer had insurance claims data showing that etanercept may lower Alzheimer’s risk by 64%.
The new research “adds further weight to the growing evidence that people who have diseases carrying a systemic inflammatory component have an increased risk of developing Alzheimer’s disease,” said Clive Holmes, MRCPsych, PhD, of the University of Southampton in England, who was not involved with the study.
“Furthermore, it clearly suggests that drugs that target peripheral inflammation — in particular, TNF inhibitors — have the potential to substantially reduce the risk of developing Alzheimer’s disease,” Holmes told MedPage Today. “Only a large randomized placebo-controlled clinical trial will definitively answer this question, but it is a question that clearly needs answering.”
This retrospective case-control study looked at electronic health records of 56 million unique adult patients from 360 hospitals and 317,000 providers, identifying patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ulcerative colitis, or Crohn’s disease. Patients diagnosed with more than one inflammatory disease were excluded from the study.
The analysis compared a diagnosis of Alzheimer’s disease as an outcome measure in patients who received at least one prescription for a TNF-blocking agent (etanercept, adalimumab, and infliximab) or for methotrexate. A patient was considered “taking a medication” if at least one outpatient prescription for the medication had been written. Patients were included in the study if they were treated with a single TNF blocker but excluded if treated with two or more TNF-blocking drugs.
Alzheimer’s risk was increased in adults with the following diagnoses (all P <0.0001):
  • Rheumatoid arthritis: adjusted OR 2.06, 95% CI 2.02-2.10
  • Psoriasis: adjusted OR 1.37, 95% CI 1.31-1.42
  • Ankylosing spondylitis: adjusted OR 1.57, 95% CI 1.39-1.77
  • Inflammatory bowel disease: adjusted OR 2.46, 95% CI 2.33-2.59
  • Ulcerative colitis: adjusted OR 1.82, 95% CI 1.74-1.91
  • Crohn’s disease: adjusted OR 2.33, 95% CI 2.22-2.43
Rheumatoid arthritis patients treated with etanercept (adjusted OR 0.34, 95% CI 0.25-0.47), adalimumab (adjusted OR 0.28, 95% CI 0.19-0.39), or infliximab (adjusted OR 0.52; 95% CI 0.39-0.69) had a reduced risk of Alzheimer’s. Methotrexate also reduced Alzheimer’s disease risk, especially for patients who had a prescription history for both a TNF blocker and methotrexate.
Psoriasis patients treated with etanercept (adjusted OR 0.47; 95% CI 0.30-0.73) or adalimumab (adjusted OR 0.41, 95% CI 0.20-0.76) also had a reduced risk for Alzheimer’s disease.
Sex or race did not affect the results, but younger patients showed greater benefit from a TNF blocker than older patients, the researchers observed.
The study had several limitations, Xu and co-authors noted. Electronic health record quality or misdiagnoses may have affected outcomes. While the analysis suggests a potential therapeutic benefit of TNF-blocking agents in Alzheimer’s, it did not look at prevention or address how disease severity might influence results.
“The anti-TNF biologics are powerful drugs that can cause severe side effects,” Gurney said. “Further studies are necessary to understand their potential in treating or preventing Alzheimer’s disease in patients who do not have rheumatoid arthritis, psoriasis, or other inflammatory diseases as risk factors for Alzheimer’s disease.”
Last Updated October 04, 2019
Xu acknowledged support from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under the NIH Director’s New Innovator Award, the NIH National Institute of Aging, and an American Cancer Society Research Scholar Grant. Gurney is an employee of Tetra Therapeutics and acknowledged support from the National Institute of Mental Health.
The researchers declared no competing interests.
Note that medRXiv is a preprint server for posting manuscripts prior to undergoing formal peer review. Data and conclusions should be regarded as preliminary until published in a peer-reviewed journal.