Kissinger Meets St. Peter

 We note that Mr. Hank Kissinger, age 100, has paid his debt to nature.

Thus he has put in appearance before St. Peter, heaven’s gate minder.

Being a man of the Judaic faith, he was rather startled to find himself there. Yet there he was.

And so he requested entry.

We have obtained a transcript of their conversation, revealed herein.

HANK: Hello, St. Peter. The Grim Reaper finally came for me. Can you believe it? And so I throw myself upon your mercy, and request entry to the heavenly realm which you guard so admirably.

PETER: There’s a saying on Earth that only the good die young. You lived to be 100. What am I to infer from this? Trust me, I have every intention of giving you a fair hearing. But let me just say it now: If I were a betting man, I would take the “under,” so to speak. And in the present context, “under” carries a literal connotation.

At any rate, let us proceed. Please hand me your dossier (Peter begins thumbing through the document.)

Your credentials are impressive indeed. You advised 12 presidents, and served as national security adviser under Presidents Nixon and Ford. You were also the only person ever to be White House national security adviser and secretary of state at the same time. Your influence over U.S. foreign policy was immense — even to your dying day. I must give you that.

HANK: (With blushing cheeks) Well, I mean, I don’t like to brag or anything, but yeah.

PETER: I see. Let’s take a little deeper look into your career, shall we? Let’s start with the Vietnam War, when you first came to prominence.

HANK: (Hesitant, voice trembling a bit) OK, s-s-s-u-u-u-u-r-e.

PETER: My records indicate that you sabotaged peace talks in 1968 in order to undermine that Johnson fellow. You believed it would grant you a higher position within the Nixon administration. Countless people needlessly died as a result. My records further indicate that you were responsible for mass deaths in Laos and Cambodia.

Let me quote from Rolling Stone magazine:

Every single person who died in Vietnam between autumn 1968 and the Fall of Saigon — and all who died in Laos and Cambodia, where Nixon and Kissinger secretly expanded the war within months of taking office, as well as all who died in the aftermath, like the Cambodian genocide their destabilization set into motion — died because of Henry Kissinger.

Is this true?

Let me remind you: You are under oath. And the penalty for perjury around here — I assure you — is quite severe.

HANK: Well, I mean, I never said I was perfect. Sometimes you have to do some unethical things for the greater good. I believed I was serving the higher good. What’s the saying? If you want to create an omelet, you need to break a few eggs.

PETER: You mean your personal ambition?

HANK: (Looking around, avoiding eye contact, fidgeting,)

PETER: You know what my boss says about killing people, right? Shall I cite the Sixth Commandment for you?

But you’re right. No one’s perfect. Perhaps you redeemed yourself in the following years. Let us see.

In 1971, Pakistan waged a genocidal campaign to suppress the independence movement that resulted in the creation of Bangladesh. Pakistan was an enemy of India and therefore a friend of China.

So you encouraged your boss, Nixon, to look the other way as Pakistani forces raped and murdered at least 300,000 people — and likely many more. Tricky Dick appeared at these very gates years ago. I asked him about this. He said you told him, “We can’t allow a friend of ours and China’s to get screwed in a conflict with a friend of India’s.”

Do you deny this, sir?

HANK: Well, no, but you have to understand the context. It was the Cold War and we were trying to drive a wedge between the Soviet Union and China. It worked and — if I can say it for myself — it represents one of the greatest foreign policy achievements in U.S. history. Again, you have to consider the greater good. We couldn’t let something like Bangladeshi independence get in the way of that.

PETER: At least 300,000 Bangladeshi would disagree with you. I admit, opening up China was a tremendous accomplishment. But at the cost of your soul?

I might further add that you set China forward 50 years. Millions of productive American jobs ended up being shipped over there, creating the Rust Belt. It also vastly expanded China’s military power, which now represents a major challenge to the United States.

I thought you were on the U.S. side?

HANK: You can’t judge me for that. The world I just departed is a complicated place. It involves trade-offs. Don’t make the perfect the enemy of the good. I helped bring millions of Chinese out of abject poverty. Isn’t that, well, rather Christian of me?

PETER: It certainly factors in your favor. And believe me, I understand your world of trade-offs. But I’m a harsh grader. Why do you think I’ve turned away so many kings, prime ministers and presidents over the millennia? But let’s move on.

Oh boy. It appears to get worse. It seems like you perfected your craft, so to speak, in South America.

In 1970, Chile elected a socialist by the name of Salvador Allende. He demanded reparations from the U.S. for appropriating its vast mineral wealth.

Before Allende’s election, you said, “I don’t see why we need to stand by and watch a country go communist due to the irresponsibility of its own people.”

You plotted a coup to have the guy overthrown. In 1973 a military junta took over. A pretty nasty bit named Pinochet took over. He tortured and killed thousands, often in —.

HANK: Now hold on, let me stop you there. Communism was evil — don’t you agree? Wasn’t I on the side of the angels here, by stopping it?

PETER: You’re correct, communism was evil. But the socialist idiot was freely and duly elected. If people want to ruin their own country, isn’t that their God-given right? Isn’t your country all about democracy? It sure likes to talk about it.

I think I know why you were so hot to overthrow that guy. It goes back to all that mineral wealth Chile had and the American corporations that were tapping it. He threatened to cut them off and you weren’t having that.

Am I correct? And remember, this is not an American courthouse. The Fifth Amendment does not apply here.

HANK: Can I plead nolo contendere — no contest?

PETER: You may if you wish. But I must inform you that I will consider your plea an admission of guilt.

HANK: Understood.

PETER: Is this the plea you wish to enter?

HANK: Yes.

PETER: So noted.

HANK: (Nodding slightly, somber in countenance.)

PETER: You know, some guy once wrote a book about you, called The Trial of Henry Kissinger. It basically accuses you of every war crime under the sun. You are aware of that — correct?

HANK: Yeah, well, I can explain THAT.

It was written by this lefty named Christopher Hitchens. Boy, did he have it in for me, let me tell you. The guy was so blinded by hatred for me, it colored everything he wrote.

PETER: Yes, I know this Hitchens character. He appeared in the very spot you stand several years ago. He was an atheist, so you should take some delight in the fact that I turned him away. You can guess where he ended up. I won’t bother telling you.

And — for the record — he was just as shocked as I was that you, a much older man, outlived him by so many years. But hey. It happens.

I nonetheless found his book about you highly compelling. He amassed a considerable amount of evidence which I can only call damning.

And I don’t use the word “damning” lightly given the serious nature of my job. I think you know what I mean.

HANK: Yes, I think I do.

PETER: Well, Kissinger, I believe I’ve seen enough. I’m ready to pronounce sentence (reaches for Hank’s dossier, seizes a stamping tool and stamps the document).

I’m sorry, but the weight of evidence against you is simply too great for me to ignore.

Entry denied! (Hands Hank his papers.)

HANK: Wait, please give me another chance! You can’t deny that I’ve actually done some good in my life.

PETER: I don’t deny it. But I’m afraid the bad you’ve done outweighs it. My decision is final. Bailiff, will you please escort the applicant to the elevator.

HANK: (Being dragged away) No, no, please don’t do this to me! I was just doing what I had to do. Damn you Nixon, look what you did to me!

PETER: Goodbye, Kissinger. Give my regards to Hitchens. You two should get along famously down there…

Brian Maher is the Daily Reckoning's Managing Editor. Before signing on to Agora Financial, he was an independent researcher and writer who covered economics, politics and international affairs. His work has appeared in the Asia Times and other news outlets around the world. He holds a Master’s degree in Defense & Strategic Studies.

https://dailyreckoning.com/kissinger-meets-st-peter/

Individuals with high Alzheimer's risk may use attention to process, not suppress, distracting stimuli

 Alzheimer's disease is a neurodegenerative condition that damages a person's ability to think, remember, and perform basic functions. According to the National Institutes of Health, Alzheimer's affects more than 6 million Americans, mostly ages 65 and older. Though the neurological damage from the disease is irreversible, its progression can be slowed by early interventions such as exercise and nutrition regimens. Thus, an early screening for Alzheimer's risk can be vital in helping people manage and plan for their symptoms.

However, before the onset of Alzheimer's physical symptoms, the primary method to measure an individual's risk of developing the disease is by measuring levels of certain proteins in cerebrospinal fluid (higher levels indicate higher risk). This test is invasive, painful, and expensive.

A team from Caltech and the Huntington Medical Research Institutes is currently conducting an ongoing project to develop a simple behavioral test to detect a person's Alzheimer's risk, as noninvasive as solving a puzzle on the computer. In 2022, the team developed a behavioral test whose results accurately correlated with spinal fluid measurements.

Now, the team has used the test to discover more about high-risk individuals' ability to pay attention and focus. The work, described in a paper appearing in the journal GeroScience, suggests that high-risk individuals are using their attention to process, rather than suppress, distracting stimuli. The research was conducted in the Caltech laboratory of Shinsuke Shimojo, Gertrude Baltimore Professor of Experimental Psychology. Shimojo is an affiliated faculty member with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

"It has been all the researchers' dream in the field to come up with a very sensitive psychological paradigm to detect subtle pre-symptoms in the high-risk elderly," says Shimojo. "However, it was nearly impossible because those high-risk elderly are not diagnosed with the current official standard tests. Our success was owing to two new twists: First, implicit cognitive processing that requires attention. And second, the hypothesis that the cognitive limitation would reveal only under high task load."

In the test, a participant completes a so-called Stroop Paradigm task. This is a common puzzle in which a person is shown a word—the word is the name of a color—displayed on a computer monitor in colored text. However, the word itself does not necessarily match the color it is displayed in—for example, the word "RED" could be displayed in the color green.

In each iteration of the task, the participant is asked to name either the color of the word or the word itself. Compared to naming the word itself, naming the color of the text is considered "high effort"—it is more challenging than it might seem. (You can try it yourself below.)

However, researchers have also added an extra twist to make the task a bit more challenging. Right before the actual target is shown, a word (white on a white background and "masked" by several meaningless symbols) is flashed rapidly on the screen—so rapidly that a participant cannot detect it consciously. (See the video to the right of the text for an example.)

The white word—technically called an "implicit distractor"—is intended to unconsciously distract the participant. In addition to conscious and intentional information gathering, which is known as "explicit cognition," our brains have the ability to process sensory information without conscious awareness. This is known as "implicit cognition."

The study involved 36 people with an average age of 75 who were cognitively healthy. Each underwent myriad tests related to Alzheimer's risk: magnetic resonance imaging (MRI) of the brain, genome sequencing, and the aforementioned invasive cerebrospinal fluid measurements. From these biological markers, individuals could be categorized as high or low risk.

In the 2022 study, the team found that individuals who were at high risk for developing Alzheimer's (as measured by their spinal fluid levels) slowed down by about 5 percent with the presence of the implicit distractor in the high-effort condition. This implicit interference was not found in the low-risk individuals. These findings suggest that implicit cognition may be altered years before the onset of any classic Alzheimer's symptoms.

The new study focused on understanding how the individuals used their attention during the test. Consider attention as a kind of currency—a finite resource your brain can spend. We all have experienced our attention being distracted from a specific task. Perhaps your phone notifications or a noisy room are distracting your attention from reading this article right now. The team aimed to determine if the high-risk population is using their attention to process the distracting word instead of suppressing the distraction and blocking it out.

"Your brain will unconsciously perceive the distracting word whether you have a high or low risk for Alzheimer's," says Shao-Min (Sean) Hung, a former postdoctoral scholar in the Shimojo group, currently an assistant professor at Waseda University in Japan and the study's co-first author. "But we wanted to study what does your brain do next? Do you use your effort to suppress the distraction, or do you use effort to process the distractor? Healthy individuals with low risk of cognitive impairment should be able to suppress the distraction."

To examine this, the team had the same volunteers complete the task twice, two weeks apart. The idea is that practice reduces the mental load of the task and allows you to have more attention available. For example, if you're an experienced soccer player, you may be able to easily dribble a ball while using some of your attention to process other things in your environment. But if you're new to soccer, you need to use a lot of attention and focus to properly dribble the ball. Practice frees up attention for your brain to use elsewhere.

The researchers found that after practicing the task, the low-risk individuals utilize their extra attention to suppress the distracting word and thus are less distracted. On the contrary, the high-risk individuals use their extra attention to process the distracting word—taking in unnecessary information that distracts them from the task at hand and results in stronger interference with their performance.

These distractions did not lead to significantly worse performance overall, but the distraction was evident in that high-risk individuals who had practice effect (faster in the second task) slowed down even more with the presence of the distracting word.

"These results suggest that there is a tight link between implicit cognition and attention, and the changes in implicit cognition in the high-risk population could reflect very early shift in how attention is utilized," says Hung.

More information: Shao-Min Hung et al, Practice makes imperfect: stronger implicit interference with practice in individuals at high risk of developing Alzheimer's disease, GeroScience (2023). DOI: 10.1007/s11357-023-00953-9

https://medicalxpress.com/news/2023-11-individuals-high-alzheimer-attention-suppress.html

"New classes of RNA for learning and memory found'

 Researchers from The University of Queensland (UQ) have discovered a new way a ribonucleic acid (RNA) impacts fear-related learning and memory.

Professor Timothy Bredy at UQ's Queensland Brain Institute said this is an exciting example of RNA's role in fine-tuning the cellular functions in the brain.

In a paper published in Nature Communications, the researchers demonstrated that a non-coding RNA known as Gas5 coordinates the trafficking and clustering of RNA molecules inside the long processes of neurons, and orchestrates neuronal excitability in real time that contributes to learning and memory.

"Understanding the complex world of RNA is a rapidly emerging area of neuroscience research, where we are constantly learning more about how different classes of RNA control the communication between and within brain cells," Bredy said.

"In this study, we found learning related RNAs at the synapse, and one in particular called Gas5, seem to be uniquely required for fear extinction memory.

"There's a lot more happening with these kinds of RNA molecules than we first thought, and that they influence cellular function on a millisecond timeframe, which mirrors the real-time changes in synaptic function that happen in the brain during learning, is extraordinary.

"Non-coding RNA may be the missing link to understanding how the brain processes critically important inputs that lead to the formation of memory."

This study builds on earlier findings from the Bredy lab that identified a separate population of learning-related RNAs that accumulate near the synapse—the junction between neurons that allow them to communicate.

In that paper, published in the Journal of Neuroscience, the team shared the discovery of several new synapse-specific RNA harboring a specific chemical tag called N6-methyladenosine (m6A).

Lead author Dr. Sachithrani Madugalle said the findings highlighted the importance of m6A-modified RNAs in regulating synaptic plasticity.

"Readers are proteins that bind to the chemical tag and direct it to locations and functions," Dr. Madugalle said.

"The readers allowed us to determine the functional role of m6A-modified RNA molecules in the formation of new memories.

"By examining one such RNA, Malat1, we discovered the key proteins that interact with this RNA and support processes related to an important type of memory called fear extinction.

"Fear extinction impairment is associated with post-traumatic stress disorder (PTSD).

"When Malat1 is chemically decorated with m6A, this allows it to interact with different proteins in the synaptic compartment, which can then alter the mechanisms involved in the formation of fear extinction memory.

"This new information may inform the development of future RNA therapies to address PTSD.

"By understanding where, when, and how an RNA molecule is activated and having a precise marker will help us identify the target for therapies."

In both studies, the team employed an innovative new tool that allowed them to manipulate the functional state of an RNA molecule, together with Professor Bryan Dickinson and Dr. Simone Rauch at the University of Chicago.

"We are now looking for ways to harness RNA to control the aspects of synaptic function underlying memory formation and to potentially develop an RNA therapeutic for the treatment of PTSD and phobia," Professor Bredy said.

More information: Wei-Siang Liau et al, Fear extinction is regulated by the activity of long noncoding RNAs at the synapse, Nature Communications (2023). DOI: 10.1038/s41467-023-43535-1

Sachithrani U. Madugalle et al, Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory, The Journal of Neuroscience (2023). DOI: 10.1523/JNEUROSCI.0943-23.2023

https://medicalxpress.com/news/2023-11-classes-rna-memory.html

EVs Have 80% More Problems Than Traditional Gas Vehicles, Consumer Reports Finds

 A new report from Consumer Reports found that electric vehicles have almost 80% more problems and are "generally less reliable" than conventional internal combustion engine cars. Good thing every major government around the world is subsidizing their use in the name of 'climate change', right?

Even worse than electric vehicles were plug-in hybrid electric vehicles, which were found to have 150% more issues than traditional ICE vehicles, CBS reported. Ordinary hybrids are the best of the breed, with about 25% less problems than gas cars, the study found. 

The study encompassed information from over 330,000 vehicles produced from 2000 to 2023, including a limited number of reports on brand-new 2024 models.

The recent vehicle reliability report from Consumer Reports coincides with a time when car purchasers have the benefit of a federal tax credit of up to $7,500 when buying an electric vehicle. 

But, as CBS noted in their summary, the adoption of EVs by consumers has been slower than initially anticipated. One contributing factor to this slower adoption is the higher maintenance costs associated with EVs compared to conventional vehicles, along with the necessity for additional equipment like home electric charging stations.

EV owners most commonly reported issues related to the battery and charging systems, as well as issues with the fit and finish of the vehicle's body panels and interior components. Consumer Reports observed that EV manufacturers are still in the process of mastering new power systems and suggested that as they gain expertise, the overall reliability of EVs would improve.

Consumer Reports also pointed out that persistent concerns about reliability are likely to compound the challenges that deter many potential buyers from transitioning to EVs. These concerns join existing ones about higher costs, limited availability of charging infrastructure, and extended charging durations associated with EVs.

CBS wrote:

"PHEVs may have more problems than conventional cars and electric vehicles because they combine internal-combustion engines with an electric drive, which creates additional complexity, Consumer Reports said. That means there's more than can go wrong."

"Consumer Reports rates vehicles on 20 problem areas, ranging from squeaky brakes to EV charging problems, and PHEVs can experience every one of them, it noted."

Not all PHEVs were horrible. According to Consumer Reports, the Toyota RAV4 Prime and Kia Sportage received reliability ratings that are above average. In addition, three plug-in hybrid electric vehicles – the BMW X5, Hyundai Tucson, and Ford Escape – achieved scores that were average. 

Jake Fisher, senior director of auto testing at Consumer Reports concluded: "This story is really one of growing pains. It's a story of just working out the bugs and the kinks of new technology."

https://www.zerohedge.com/markets/evs-have-80-more-problems-traditional-gas-vehicles-consumer-reports-finds

Congress Must Hold The CDC Accountable For Cozy Ties To Pharma

 by Paul Thacker via The Disinformation Chronicle,

Congressional leaders with the House Energy and Commerce investigative subcommittee will question CDC Director Mandy Cohen tomorrow in what should be an interesting hearing on restoring public trust.

The hearing “should” be interesting, because this committee has a long history of holding corporate and government leaders accountable.

However, we have yet to see this committee get any actual explanation for a rash of mistakes and failures during the COVID pandemic.

During her final appearance before Congress last summer, the prior CDC Director, Rochelle Walensky, gave false testimony about a study on masks. When two researchers pointed out Walensky’s mistake, a congressional staffer emailed them that the committee would correct the record. “We want the record to reflect the accurate facts for posterity,” the staffer with House Appropriations wrote, “And take this responsibility very seriously as the lack of trust in public health officials is becoming an enormous problem for many reasons.”

Having run congressional investigations for several years, I’m confused why the Energy and Commerce committee has done so little peeking into COVID scandals at the CDC—many of which I have documented during the last couple of years. Congressional staff work long hours and often don’t have the time to look into every problem, but how can the CDC regain public trust when employees with the PR firm for Pfizer and Moderna staff the CDC’s Vaccine Center?

Last October, I discovered that employees with the global PR firm Weber Shandwick are embedded at the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), the CDC group that implements vaccine programs. Weber Shandwick won this multi-million dollar CDC contract back in September 2020, during COVID pandemic’s first year. 

A few weeks after Weber Shandwick won the CDC contract, a senior vice president at the firm posted a company blog that disclosed Weber Shandwick clients working on COVID-19 vaccines included GSK, Sanofi, and Pfizer. A special investigation by PR Week reported that Weber Shandwick provided publicity for Moderna’s COVID vaccine.

“So excited to be starting a new role today,” one Weber Shandwick employee wrote on her LinkedIn account. “I’m joining Weber Shandwick as an Account Director supporting a contract I know well, at CDC’s NCIRD!”

Weber Shandwick employees staffing NCIRD help to run the CDC Advisory Committee on Immunization Practices (ACIP). After ACIP recommended recommended in late 2021 that everyone over 12 receive a “bivalent” Covid-19 vaccine as a booster dose, Dr. Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, warned that ACIP’s advice was made without convincing data.

Despite sending a slew of emails to the CDC—some directly to the CDC Director—I never got an explanation for this obvious conflict of interest. Senator Rand Paul later sent the CDC a letter, but the agency ignored him. Will the House Committee demand answers?

Share

Paul D. Thacker is an American journalist who reports on science, medicine, and the environment. He was a lead investigator of the United States Senate Committee on Finance for Senator Chuck Grassley, where he examined financial links between physicians and pharmaceutical companies.

https://www.zerohedge.com/political/thacker-congress-must-hold-cdc-accountable-cozy-ties-pharma

Don't Let Bureaucracy Impede Research for ALS, Says Ethicist

 Hi. I'm Art Caplan. I'm at the Division of Medical Ethics at the Grossman School of Medicine at NYU in New York City.

Amyotrophic lateral sclerosis (ALS) is a horrible disease. Some of us know it as Lou Gehrig disease, and it involves creeping paralysis, certain death, horrible disability, confinement to a wheelchair, and many people wind up only able to operate a computer screen to message. It is just a miserable disease. People have been trying to find ways to intervene, to fix it, to cure it, and to slow it.

Unfortunately, some patients, families, and some others believe that the biggest obstacle to getting the answer to ALS is the FDA and regulations. They believe that regulations are causing bureaucrats to slow down potentially beneficial interventions.

They believe that regulations and the FDA are indifferent to the suffering of patients, paying more attention to data analysis, wondering more about the certainty with which a particular claimed cure or intervention really can help, and not letting patients who are desperate make or take a risk-benefit choice, given their dire straits, that they are willing to try things and to gamble that something might help them. Even as some patients say: If it kills them or they die more quickly… Well, the disease is so bad that they would like to be able to make that choice.

Legislation has been introduced in the House of the Senate called the Promising Pathway Act, basically pushed forward by many ALS organizations, that would expedite a review by the FDA. It says the FDA should establish a rolling, real-time review, meaning taking a look every day, technically, at drugs that are intended to treat, prevent, or diagnose life-threatening diseases.

On this pathway, the FDA could grant a sort of limited approval, letting a drug that has some evidence of safety get out to the public and maybe has some promise that there's efficacy. The way that would be determined is not by a clinical trial, not by a study, but basically by real-world evidence, including claims from patients and family members that they feel better, they think they're doing better, and that they think the drug that a company is trying to get approval to sell is really doing something.

I think this is wrong, and it really is painful for me to say it. I think the difficulty with fighting and finding help for those with ALS or preventing it is not the FDA, it's the science. We just don't understand this disease very well. The science just isn't in a position yet to say we're going to be able to offer some benefits. Various drugs have been brought forward and presented to the FDA. The experts have taken a look at them, and they say they're just not convincing in terms of conveying any real benefit.

Desperation, of course, makes people want to try anything, but it doesn't mean that the science that's out there supports it nor does it mean that entrepreneurs and investors who want to sell things to ALS patients, who want to get the government to approve reimbursement for their drugs, are really telling us honestly what they are capable of doing. Sometimes, even they work with patient groups to try to get them to agitate Congress, the FDA, or both to provide approval so they can then get reimbursed.

This is a tough area. There are many little companies that, if they don't get their drug approved for some use, are not going to make it. The company won't survive because it doesn't have much money. There are other situations, where patients are saying, don't protect us from harm or a lack of efficacy. There are still others saying, look, if you approve some of these drugs and the price tags are hundreds of thousands of dollars per patient or millions, you're going to wind up spending a fortune on something that may not work at all.

I don't think the time has come to pass the Promising Pathway Act to try to have temporary approvals, less evidence, and allow more sketchy claims to be put forward as a basis for a temporary approval of a drug.

I think we still have to be tough and say that we need to get drugs into controlled clinical trials, then use claims from patients, real-world evidence, to supplement what the data are in the trials. There's no replacing clinical trials of drugs with patient stories and narratives built up by the company. That's just not the way to get the public's or the patients' interests served at a time when the science is still tough and not there for cracking ALS.

It's sad to say it, but I wouldn't put my money into efforts to reduce the bureaucracy. I'd put my money into more research, more rapid research, and bigger research projects.

https://www.medscape.com/viewarticle/998184

Not All Exercise Is Beneficial: The Physical Activity Paradox

 In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity — with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

"Incorporating a life-course perspective gives a broader picture of how participants' occupational histories relate to cognitive impairment later in life," principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York City, told Medscape Medical News. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual's career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required "considerable" use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers conclude that "consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment."

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.

Good vs Bad PA

Kirsten Nabe-Nielsen, PhD, lead author of this study, is quoted as saying, "[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a 'good' form of physical activity, which hard physical work is not."

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of US data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were "always" performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with "never" engaging in these activities.

"Our national guidelines for PA include occupational activity," lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, told Medscape Medical News. "But it's clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not getting benefits from it."

The contrasting effects of leisure-time vs occupational PA constitute the "physical activity paradox" hypothesis. Starting in 2011, multiple studies by Andreas Holtermann of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only "marginally considered" until a few years ago, recent large cohort studies seem to confirm the paradox, writes Pier Luigi Temporelli, MD in a recent editorial.

In separate interviews, Skirbekk and Quinn pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

"It's well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite," Skirbekk said. "The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance."

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

"We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers," he said. "You cannot sit. You have somebody relying on you. It's not all pleasure, and it can be very hard. That's where we find the associations."

Lack of Autonomy

Specific characteristics indirectly associated with high occupational PA jobs — low cognitive stimuli, lifestyle factors, and socioeconomic influences — as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Skirbekk explained.

"By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers," he said. "It may also be that too little or too much PA could be adversely related to cognitive outcomes — hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning."

Quinn said most of the CVD risk linked to occupational PA, has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they're not as risky as lifting and carrying, he said.

Like Skirbekk, Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn't have that same autonomy to allow for recovery.

"So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest," Quinn said.

"We've shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non–workdays," he said.

Quinn also said that psychological stress at work amplifies risk. "A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn't have psychological stress combined with it."

Research Gaps

However, Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. "It is often difficult to change professions, and even if you do, it won't immediately affect cognition. But altering one's lifestyle is likely to have effects on cognitive development across the life cycle.

"Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes — stopping smoking, eating well, getting proper sleep, etc. — affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient's occupation into account during any evaluation," Skirbekk noted.

Quinn said it isn't realistic to expect workers to come up with solutions to the PA paradox because many don't have the autonomy to be able to mitigate their occupational risk.

"I think administrative controls and policy changes eventually will be the levers of change. We're not quite there yet, but those are the types of things we should do when we're trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad," he said.

However, not everyone agrees that occupational PA doesn't confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

"Even studies coming out now regarding the effects of occupational PA have mainly used older data," Skirbekk noted. "Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that's happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be."

Health Inequity Issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. "Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases."

Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Skirbekk and Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

"Our national guidelines for PA include occupational activity," said Quinn. "But it's clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefitting from it."

Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore "improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe."

https://www.medscape.com/viewarticle/998772