'Primitive Reflexes May Predict Dementia'

 

• Frontal release signs predicted higher 7-year dementia risk in cognitively normal adults.
• These signs are simple neurologic exam findings associated with brain injury or neurodegeneration.
• Frontal release signs include primitive grasp, snout, and rooting reflexes.

Primitive or regressive reflexes -- known as frontal release signs -- later in life were associated with increased dementia risk, a longitudinal study of cognitively normal older adults showed.

In adults with intact cognition, the presence of two or more frontal release signs was associated with a significantly higher risk of progressing to dementia over 7 years (HR 1.78, 95% CI 1.02-3.09), reported Lauren Bojarski, DO, MS, of West Virginia University in Morgantown, and colleagues in JAMA Network Open.

Frontal release signs are present in newborn children and gradually disappear as the brain matures in early life. They include the Myerson sign (an inability to resist blinking when repeatedly tapped between the eyebrows), and grasp, snout, rooting, and palmomental reflexes. Reappearing signs are associated with brain injury or neurodegeneration and can be seen in late-life dementia.

Signs of frontal release are easy to assess and traditionally have been considered part of a standard neurologic exam. While individual signs have shown relatively low sensitivity and specificity for detecting injury or degeneration, a meta-analysis of 29 studies found that people with dementia were up to 16 times more likely to exhibit frontal release signs, with the grasp reflex showing the strongest link.

"As biomarkers become increasingly integrated into the dementia diagnostic pathway, we must remember that clinical acumen remains paramount. A meticulous neurologic examination yields invaluable diagnostic insight, yet we are seeing a concerning decline in the foundational neurology rotations essential for training the next generation of clinicians," Bojarski said.

"By demonstrating the enduring utility of the clinical exam and prioritizing these bedside skills in medical education, we can ultimately foster greater diagnostic accuracy and therapeutic confidence," she told MedPage Today.

Bojarski and co-authors followed 873 older adults from the University of Kentucky Alzheimer's Disease Research Center (ADRC) cohort in Lexington from 2005 to 2024. Participants were cognitively intact (672 participants) or had mild cognitive impairment (201 participants) at baseline; they had a mean age of 76.9 and an average of 16.1 years of education. Most (60.4%) were women.

Follow-up was 7.2 to 7.5 years on average in the cognitively intact group, and 4.0 to 4.4 years in the group with mild cognitive impairment.

Participants had at least two assessments that included standard protocols involving frontal release signs. Each annual evaluation included a medical history, a physical examination, and an extensive battery of neuropsychological tests of cognitive status.

At baseline, participants were classified as positive or negative for frontal release signs; those who had two or more signs were considered positive. In the intact cognition group, 8.8% were positive for frontal release signs; in the group with mild impairment, that proportion was 23.9%.

In the cognitively intact group, 25.4% of people with two or more frontal release signs progressed to dementia compared with 14.5% of people with one or no signs. Models adjusted for baseline age, sex, and education showed that mean scores in memory and executive domains worsened in this group over time.

Among participants with mild impairment at baseline, there was no difference in domains. No significant relationship between frontal release signs and dementia risk emerged.

This study was based on findings from a single ADRC, Bojarski and colleagues acknowledged. The cohort included people with relatively homogenous racial demographics and high education levels.

Frontal release signs can support tests and biomarkers to help determine who might develop dementia, the researchers pointed out. "Classic neurologic examination techniques like checking frontal release are gradually being replaced by sophisticated biomarkers and genetic testing, yet the importance of the neurologic exam for interpreting such biomarkers has never been greater," observed co-author Gregory Jicha, MD, PhD, of the University of Kentucky.

"We should not lose the art of the neurologic exam, as it adds incredibly to our diagnostic formulation," Jicha told MedPage Today. "We hope the future generations of neurologists do not simply look at a lab value to diagnose and treat, but rather that they fully examine and understand the patient and their neurologic condition in order to provide optimal care."

Disclosures

This study was supported by a grant from the National Institute on Aging, which funds the University of Kentucky Alzheimer's Disease Research Center.

Bojarski reported no conflicts of interest. Jicha disclosed relationships with Alnylam, Cognition Therapeutics, Eisai, and Novo Nordisk. Other study authors had no conflicts.

Primary Source

JAMA Network Open

Source Reference: Bojarski LG, et al "Frontal release signs and future decline in research participants with intact cognition" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2026.17060.

https://www.medpagetoday.com/neurology/dementia/121660

Tolerability Concerns for GLP-1/Glucagon Agonist in Obesity, MASLD

 Treatment with survodutide led to significant weight loss and reductions in liver fat in phase III trials of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), but about a fifth of patients quit the investigational glucagon and GLP-1 receptor dual agonist due to adverse events.

Obesity Trial

In the SYNCHRONIZE-1 trial of people with obesity but without diabetes, mean body weight loss by week 76 with treatment plus lifestyle modification counseling reached 12.2% in the 3.6-mg once-weekly survodutide group and 13% in the 6.0-mg once-weekly group as compared with 5.4% with placebo, reported Carel le Roux, MBChB, PhD, of the University College Dublin School of Medicine.

"Body weight reduction with survodutide was driven predominately by loss of fat tissue," le Roux said at the American Diabetes Association (ADA) Scientific Sessions. The findings were simultaneously published in the New England Journal of Medicine.

However, gastrointestinal adverse events -- primarily nausea, vomiting, diarrhea, and constipation -- occurred in 80.9-89.7% of the survodutide groups and in 47.9% of the placebo group. These events led to 17.8-20.2% of the survodutide groups discontinuing the study treatment compared with 2.9% of the placebo group. No deaths were reported.

Obesity medication development is entering a new era of combining GLP-1 agonists with other agonists of glucagon, gastric inhibitory polypeptide (GIP), or both.

"The development of glucagon receptor-GLP-1 receptor dual agonists to enhance the relative potency of the agonists at these receptors has been challenging, particularly with respect to net effects on glucose homeostasis," the authors wrote. "In this trial, treatment with survodutide did not increase glycated hemoglobin levels in participants without diabetes mellitus; a previous phase 2 trial involving persons with obesity and type 2 diabetes showed that survodutide significantly reduced glycated hemoglobin levels."

The double-blind trial was conducted at 116 clinical sites across 14 countries. All 725 participants had either a BMI of at least 30 or at least 27 with an obesity-related complication other than diabetes. The cohort averaged 47.1 years of age, baseline BMI of 37.9, and body weight of 239.9 lb (108.8 kg). Slightly more than 40% of participants were men.

Participants were randomized 1:1:1 to once-weekly survodutide doses adjusted up to 3.6 mg or 6 mg or placebo. Patients were also encouraged to follow a reduced-calorie diet and to exercise.

Dose flexibility was initially limited to weeks 16 to 32 after randomization, and participants were told to discontinue the study treatment if three or more doses were missed due to gastrointestinal reasons or other causes.

"This study was set up specifically to be very rigid," le Roux said, explaining the high drop-out rate. "We wanted a rigorous result, we wanted an end result that you look at and say, 'I trust these numbers.' But sometimes, you can overshoot. Sometimes in your pursuit of rigorous results, we made it so difficult for patients to stay in this study that actually they had to step out because they couldn't increase the dose because of the forced titration."

"That also allows you and me to go back to clinic next week and think about what are the benefits and risk-benefit ratio between being very rigid and having more flexibility. Thinking about how we can keep people in our clinical trials but also our clinical practice ... and be more gentle with our patients," he noted.

MASLD Study

Survodutide also showed benefit for MASLD patients with obesity, according to the phase III SYNCHRONIZE-MASLD study, also presented at ADA.

Among 216 adults, 68.5% of survodutide-treated patients and 28.6% of placebo-treated patients had at least 30% reduction in MRI-proton density fat fraction-assessed liver fat content in the treatment regimen estimand by week 48 (P<0.0001) -- a degree of reduction previously linked to a higher likelihood of histologic improvement and resolution of metabolic dysfunction-associated steatohepatitis (MASH).

These data "suggest the potential for survodutide treatment to support meaningful improvement in several of the proposed drivers of MASH and hepatic fibrosis, addressing an area of high unmet need," a team led by Lee Kaplan, MD, PhD, of the Obesity and Metabolism Institute in Boston, wrote in a simultaneously published paper in Nature Medicine.

The average body weight reduction over 48 weeks was 8.7% with survodutide and 1.4% with placebo (P<0.0001) in the same treatment regimen estimand used in the SYNCHRONIZE-1 trial, a conservative assessment with missing data in the survodutide arm assumed to be similar to that in the placebo arm.

Gastrointestinal events in this study were also commonly reported during the dose-escalation phase but were generally of mild-to-moderate severity. Still, 19.9% of participants in the survodutide group discontinued treatment versus 4.3% of those in the placebo group.

Participants, who were recruited from the U.S. and Spain, all had MASLD with evidence of liver inflammation or fibrosis by noninvasive tests or biopsy-confirmed MASH. Participants were randomized 2:1 to treatment with survodutide 6 mg once weekly or placebo.

Survodutide is also being studied in two global phase III clinical trials -- LIVERAGE and LIVERAGE-Cirrhosis -- investigating the efficacy and safety of survodutide in adults with MASH and stage 2 or 3 fibrosis and in those with compensated MASH cirrhosis (stage 4 fibrosis).

Disclosures

The trial was funded by Boehringer Ingelheim.

Le Roux disclosed relationships with AbbVie, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Currax Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche AG, Johnson & Johnson, Medscape, Medtronic, Metsera, Morphic Therapeutic, Novo Nordisk, Nymble, Olympus, Pfizer, and Zealand Pharma A/S.

Kaplan reported relationships with Altimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Dexligo, Dil Figaro, Eli Lilly, Helicore, Johnson & Johnson, Kallyope, The Last Food Fight, MetaVia, Neurogastrx, Novo Nordisk, Optum Health, Oxford Medical Products, Perspectum, Pfizer, Roche/Genentech, Skye Bioscience, State 4 Therapeutics, Structure Therapeutics, and Wave Life Sciences.

Primary Source

New England Journal of Medicine

Source Reference: Le Roux CW, et al "Survodutide once weekly for the treatment of adults with obesity" N Engl J Med 2026; DOI: 10.1056/NEJMoa2600751.

Secondary Source

Nature Medicine

Source Reference: Kaplan LM, et al "Survodutide in adults with obesity and metabolic dysfunction–associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial" Nat Med 2026; DOI: 10.1038/s41591-026-04479-3.

https://www.medpagetoday.com/meetingcoverage/ada/121663

'Iran, allies can open new fronts, deputy chief of Khamenei's office warns'

 

If Israel and the United States take steps to expand tensions, the Islamic Republic and its allies have both the capability and the will to open new fronts, Rasoul Sanaei-Rad, a political deputy in the Supreme Leader's ideological-political office, warned on Monday.

https://www.iranintl.com/en/liveblog/202606062776

Xi Jinping Applauds Kim's 'Socialist Cause' In Warm North Korea State Visit

 North Korean leader Kim Jong Un warmly greeted Chinese President Xi Jinping in Pyongyang Monday, kicking off Xi's two-day state visit to the internationally isolated country - which is his first trip there in seven years.

Xi has called for deepening "strategic coordination and cooperation" with North Korea shortly after receiving a lavish, red carpet welcome at the airport. The two sides should inject "powerful momentum" into their ties, Xi said according to a readout released by Chinese state media Xinhua.

Xinhua/ZUMA Press

The Chinese leader spoke of a friendship that was 'generational' with the DPRK, in advancement of the 'socialist cause'.

There is plenty that is ideological found within the official readout in the wake of the two leaders' initial meeting, per Xinhua:

No matter how the international situation changes, the Chinese party and government's firm stance on highly valuing China-DPRK traditional friendship will not change, the firm support for General Secretary Kim in leading the DPRK's socialist cause will not change, and the firm commitment to safeguarding the shared interests of the two countries and preserving a favorable strategic environment will not change, Xi said.

Xi pointed out that, in the face of the profound changes unseen in a century that are accelerating across the world, the two sides should take a broad and long-term view, build on past achievements and open up a new future, draw wisdom from the development process of the relations between the two parties and the two countries, seize opportunities in the prevailing trend of human history, inject new contemporary connotations and strong impetus into the traditional friendship between China and the DPRK, and open up a brighter prospect for the socialist cause of the two countries as well as regional peace and development.

This cooperation is expected to be on several fronts, including economics and trade, agriculture, health, construction, as well as science and technology, Xi underscored.

Kim along with his first lady, Ri Sol Ju, enthusiastically greeted Xi and were shown clapping as the Chinese presidential plane touched down earlier in the day. Huge portraits of Xi and Kim have been installed over Pyongyang's main Kim Il Sung Square, where Xi's motorcade was also greeted with big displays of pageantry, including a mounted cavalry escort.

NBC has some interesting commentary which points out that Kim is in a rare position of strength based on some recent firm, anti-West geopolitical stances taken and maintained:

But the North Korean leader is playing host from a position of rare strength, and his country has come a long way since Xi Jinping’s last visit seven years ago.

Kim’s backing of Russia’s war with Ukraine has paid dividends, his weapons program has cemented North Korea’s status as a de facto nuclear state, and an economy that buckled under the pressure of pandemic isolation and sanctions has since rebounded.

Indeed, Kim has of late been aggressively hyping his country's nuclear modernization and expanse program. There's not doubt he's also closely following and taking notes on the Iran crisis. 

Iran, which does not yet have nuclear weapons status, has been attacked by the United States and Israel - and so Pyongyang sees its nuclear expanse path as more justified than ever at this point, also given Washington still views North Korea as a 'pariah' state.

Another interesting development mentioned in state media relates to efforts to open borders: "Xi called on both sides to leverage the opportunity of the full reopening of border crossings and the resumption of civil aviation flights and international passenger trains to increase people-to-people exchanges and foster mutual interaction," wrote Xinhua.

https://www.zerohedge.com/geopolitical/xi-jinping-praises-kims-upholding-socialist-cause-rare-north-korea-state-visit

On The Kavanaugh Anniversary, Democratic Leaders Swap Me Too For Maine

 by Jonathan Turley,

...on the eighth anniversary of the Kavanaugh nomination. It now appears that there are some women who are not to be believed... when the Senate may be in the balance..

“It’s clear the fix is in.”

Those words from Sen. Elizabeth Warren (D-Mass.). came with her vote against confirming Brett Kavanaugh to the Supreme Court. Warren was outraged that her fellow senators refused to believe a woman who came forward with a decades-old allegation against Kavanaugh that lacked any corroboration.

It now appears that Kavanaugh’s former accusers are making the case that he was treated unjustly at their hands. At least they are now willing to swap “Me Too” for Maine.

Warren’s words were part of a mantra from Democratic members that either you believe women about sexual harassment and assault, or you are enabling abusers.

It was almost exactly eight years ago, in July 2018, that President Trump nominated Kavanaugh to fill the seat of retiring Associate Justice Anthony Kennedy. Kavanaugh, who was at first a very uncontroversial nominee, suddenly became the target of a well-financed, well-orchestrated campaign that would continue to resonate in that fall’s election campaigns. At the time, your failure to accept the word of Christine Blasey Ford that Kavanaugh had assaulted her in high school was just proof that you and the system were sexist.

Long after the Senate confirmed Kavanaugh, the left continued to claim that his presence on the Supreme Court “rests on a mountain of misogyny.” In Ms. Magazine, actress Kathleen Turner reminded people that not believing women was furthering misogyny: “Survivors who come forward break the rules of silence a sexist society demands, and society expects them to pay a price.”

If you recall, the lack of evidence led to the Senate Judiciary Committee combing through Kavanaugh’s personal calendars. Denials that such a thing had ever happened, coming from childhood friends, were treated as still more evidence of sexism.

Screenshot/Judiciary Committee

There was Sen. Sheldon Whitehouse (D-R.I.), who grilled Kavanaugh about using the term “boofing” (apparently referring to passing gas) with a high school friend as if it were a confession to a rape.

His inquisitorial barrage was something straight out of the McCarthy period.

Whitehouse expressed disgust that some would not take Ford’s word for it, declaring, “Today I stand with women who are brave enough to come forward with their stories of abuse and mistreatment. They deserve to be heard and credible allegations must be investigated. We must believe survivors, not bully them.”

Whitehouse is now a major donor and supporter of Graham Platner, the leading Democratic candidate for U.S. Senate from Maine.

He dismisses the New York Times accounts from women of Platner’s physically and mentally abusive behavior.

Instead of believing these women, he reportedly attacked Lyndsey Fifield, who “bravely” came forward publicly with her story at the request of Times reporters.

Whitehouse is quoted as saying that he was “unimpressed” by the allegations and the multiple women coming forward “seems like a lot of nothing.” He suggested that he is not prepared to believe a woman if she is a conservative. “I mean, the only one who had anything to say that seemed ‘unsettling’ was a woman who works for right-wing political operations,” he said.

That attack was picked up by others like writer Krystal Ball. She too had denounced those who did not believe Ford in the Kavanaugh controversy. In the past, she claimed at that time, “women just didn’t come forward. They knew they wouldn’t be believed.”

Now she cannot imagine why anyone would believe these women, particularly Fifield. “NYT published uncorroborated accusations against [Platner] of ‘unsettling’ and ‘toxic’ behavior that came from a Heritage staffer who previously worked for a conservative org that backs Collins,” she posted online.

Fifield, after sharing stories with the Times of Platner’s alleged abusive behavior, went public to complain that the newspaper had failed to include the corroboration she had provided. She posted that the paper not only failed to include that she has supported Democrats for office, but also asked, “Why does it say ‘nobody could corroborate’ when I offered them sources that COULD corroborate?”

She added, “The Times also failed to include any mention that I DID confide in multiple friends through the years that Graham had been abusive — long before he was running for office. Those friends confirm they told the Times so.”

If true, that is a strikingly different approach from the one taken by the media in reporting on the Kavanaugh allegations.

All the familiar faces are now attacking or dismissing these allegations.

That includes Rep. Ro Khanna (D-Calif.), who campaigned for Platner this week. Khanna had previously pounded his chest in public over the Kavanaugh allegations: “I believe Dr. Christine Blasey Ford.”

Some of the usual suspects are now quiet, and for good reason. Former New York Gov. Andrew Cuomo (D) and former Rep. Eric Swalwell (D-Calif.) dismissed Kavanaugh’s claims of innocence but later resigned from their respective offices after accusations of misconduct and harassment.

Of course, the sexual misconduct and mistreatment of women is not the only controversy surrounding Platner, who has reportedly ridiculed a wounded veteran, dismissed rape victims, and made other comments on his since-deleted Reddit account about Blacks and rural Mainers that would be considered disqualifying for most candidates. He made many other posts that were deeply offensive and some that were, frankly, gross.

Nevertheless, figures like Senate Minority Leader Chuck Schumer (D-N.Y.) would not even address the allegations, simply repeating awkwardly, “We’re going to … take back the Senate.”

Back in 2018, Schumer was proclaiming on the Senate floor, “For too long, when women have made serious allegations of abuse, they have been ignored. That cannot happen in this case.”

For her part, Sen. Kirsten Gillibrand (D-N.Y.) proclaimed her faith in any woman making such allegations in 2018. Now, she repeats, like Schumer, “I’m very optimistic we’re going to win Maine.”

In “A Man for All Seasons,” there is a scene where Sir Thomas More confronts Richard Rich, a former protege who lied in court to convict him in exchange for being named attorney general of Wales. As Rich passes by, More asks: “For Wales? Why, Richard, it profits a man nothing to give his soul for the whole world … but for Wales!”

The response by Democratic leaders today appears to be, “Well, yeah — not for Wales, but we’ll do it for Maine.”

Jonathan Turley is a law professor and the New York Times best-selling author of “Rage and the Republic: The Unfinished Story of the American Revolution.

https://www.zerohedge.com/markets/kavanaugh-anniversary-democratic-leaders-swap-me-too-maine