A structured multidomain lifestyle intervention may help slow changes in brain white matter associated with aging, a secondary analysis of data from the randomized POINTER trial suggested.
Compared with a self-guided intervention, a structured intervention attenuated increases in white matter free water over time (β = -0.031, SE=0.012, P=0.009) in people under age 70, reported Pauline Maillard, PhD, of the University of California Davis, who presented findings from the POINTER Imaging analysis at the Alzheimer's Association International Conference.
This effect was not seen in participants 70 and older, and no comparable intervention-related interactions were detected for other cerebrovascular MRI markers studied, Maillard and colleagues noted in JAMA Network Open, where the study was published.
"This study provides evidence that a multidomain lifestyle intervention may help slow changes in brain white matter that are associated with aging and cognitive decline," Maillard said. It suggests earlier intervention, before age 70, may be especially beneficial for preserving brain health, she observed.
"White matter changes are often less emphasized than memory-related brain changes, but they are closely linked to vascular health, brain connectivity, and cognitive function," Maillard told MedPage Today. "Our findings support the idea that addressing several modifiable risk factors together, including physical activity, diet, cognitive and social engagement, and cardiovascular health, may have measurable effects on the brain."
"These results should not be interpreted as showing that lifestyle intervention can prevent dementia on its own, but they provide encouraging biological evidence that lifestyle changes may influence brain aging," she emphasized. "Longer follow-up will be important to determine whether these imaging differences translate into sustained cognitive benefits."
The POINTER trial tested two lifestyle interventions -- one structured, the other self-guided -- to see whether they would improve cognitive scores in over 2,000 older adults. Both 2-year interventions encouraged physical activity, cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but they differed in structure, intensity, and accountability.
The primary findings, published in 2025, demonstrated greater cognitive benefits in the structured group compared with the self-guided group. The researchers estimated that the structured intervention slowed the cognitive aging clock by about 1 to 2 years.
Data from three of the trial's ancillary studies -- POINTER-NV (neurovascular), POINTER-Neuroimaging, and POINTER-zzz (sleep) -- showed that blood pressure regulation, cognitive resilience, and sleep apnea were better with the structured intervention.
In the POINTER Imaging analysis, Maillard and colleagues evaluated 959 participants with a mean age of 68 years; 61.9% were women. Participants underwent MRI at baseline and at up to two follow-up visits at 12 and 24 months.
The primary outcomes were cerebrovascular MRI markers of global white matter free water, fractional anisotropy, peak width of skeletonized mean diffusivity, analysis along the perivascular space index, white matter hyperintensity volume, and incident cerebral microbleeds. Free water was the marker most responsive to lifestyle intervention in adults 60 to 70 years of age, showing attenuated small-vessel disease-related injury, Maillard said.
Baseline free water also identified participants at higher risk for white matter hyperintensity progression and incident cerebral microbleeds, she added.
The imaging cohort was an ancillary subset with a slightly lower proportion of women and a modestly higher prevalence of vascular risk factors than the main study cohort, the researchers acknowledged. The 2-year timeline may be insufficient for tracking certain vascular outcomes.
During the meeting, the Alzheimer's Association announced a new study based on findings from POINTER and the LatAm-FINGERS study, which showed that a multidomain lifestyle intervention in Latin America led to greater cognitive improvements versus a flexible health-advice intervention.
The global PROTECT-Cog trial will test whether a lifestyle intervention combined with a GLP-1 receptor agonist or similar metabolism-targeting drug can help prevent or delay cognitive decline and dementia, the group said.
"PROTECT-Cog builds directly on what we learned from U.S. POINTER and takes the next critical step in prevention science," Maria Carrillo, PhD, chief science officer and medical affairs lead at the Alzheimer's Association, said in a news release. "By testing a combined approach that targets both lifestyle and biology, we have the opportunity to better understand how to meaningfully reduce the risk of cognitive decline before symptoms begin."
Disclosures
This study was supported by the National Institute on Aging and by the Alzheimer's Association.
Maillard has no disclosures.
Adding a GLP-1 receptor agonist was not associated with a lower likelihood of discontinuing existing basal insulin therapy among veterans with type 2 diabetes compared with other glucose-lowering agents, a target emulation trial found.
Over a 3-year follow-up, insulin therapy was discontinued by 16.7% of GLP-1 drug initiators, 17.9% of SGLT2 inhibitor initiators, and 17.1% of DPP-4 inhibitor initiators in an intention-to-treat analysis, according to researchers led by Kasia Lipska, MD, MHS, of the Veterans Affairs Connecticut Healthcare System in West Haven.
Neither difference in insulin discontinuation reached statistical significance, with risk ratios of 0.93 (95% CI 0.86-1.01) for GLP-1 drugs versus SGLT2 inhibitors and 0.98 (95% CI 0.87-1.09) for GLP-1 drugs versus DPP-4 inhibitors.
The findings held true in a modified per-protocol analysis as well, and GLP-1 receptor agonists showed no comparative advantage over the other two drug classes in any specific patient subgroup.
"Although GLP-1 receptor agonists remain valuable for their cardiovascular, renal, and weight benefits, their initiation alone does not seem to drive basal insulin discontinuation beyond that observed with other glucose-lowering agents," Lipska and co-authors concluded in Annals of Internal Medicine.
About 20-30% of people with type 2 diabetes require insulin therapy to maintain glycemic control. However, insulin regimens can be "complex and burdensome," the authors noted, requiring multiple daily injections, ongoing dose adjustments, and frequent monitoring. Insulin also carries risks for hypoglycemia and weight gain.
"With the growing use of GLP-1 receptor agonists, questions have emerged about whether their addition enables safe and effective discontinuation of insulin therapy for people with type 2 diabetes," Lipska and colleagues explained.
Some prior studies have shown a substantial reduction in total daily insulin doses when GLP-1 drugs are added to the regimen. For example, the SUSTAIN-5 trial found that once-weekly 1-mg semaglutide (Ozempic) led to a 15% reduction in insulin dose compared with placebo.
Mechanistically, GLP-1 drugs might reduce insulin requirements by enhancing glucose-dependent insulin secretion, suppressing glucagon release, delaying gastric emptying, and curbing appetite, leading to substantial weight loss and improved insulin sensitivity. Additionally, the blockbuster class of agents has been shown to reduce postprandial glucose excursions, which may allow for basal insulin dose reductions.
However, these physiologic effects might be insufficient to permit full discontinuation of insulin, particularly in patients with long-standing disease or limited residual beta-cell function, Lipska and co-authors noted.
"Understanding how often insulin can be withdrawn after initiating a GLP-1 receptor agonist has important implications for clinical guidelines, treatment burden, cost, and long-term outcomes," they wrote.
To address this, the research team designed a target trial emulation to evaluate the effects of GLP-1 drug initiation on rates of insulin discontinuation using U.S. Veterans Health Administration electronic health record data.
They compiled 8,869 matched sets of GLP-1 receptor agonist initiators (76.6% semaglutide, 15.2% dulaglutide [Trulicity], 7.9% liraglutide [Victoza], and 0.3% exenatide [Byetta, Bydureon]), SGLT2 inhibitor initiators (99.7% empagliflozin [Jardiance]), and DPP-4 inhibitor initiators (95.9% alogliptin [Nesina]). All participants initiated treatment from 2020 to 2022. The cohort was 93% male, 63% were 65 or older, 70% were white, and 48% had an HbA1c of 9% or higher.
The researchers pointed to several real-world factors that might explain the minimal differences in insulin discontinuation rates across the treatment groups.
First, the efficacy of GLP-1 drugs observed in clinical trials might not fully translate to real-world settings, where patient selection, medication adherence, step therapy, and formulary restrictions all play a role. For instance, fewer than 10% of patients in this study actually reached the maximum dose of their GLP-1 drug during the 3-year follow-up.
Additionally, there were high treatment crossover rates during follow-up, such as patients initiating an SGLT2 inhibitor but later switching to a GLP-1 agent. Other limitations of the study included a reliance on administrative and pharmacy claims data, which may misclassify medication exposure or insulin discontinuation.
Future research should look into whether dual- or triple-incretin agonists, which can produce greater glycemic and weight reductions, have a different impact on insulin discontinuation in routine clinical practice, Lipska and colleagues suggested.
Disclosures
The study was funded by the U.S. Department of Veterans Affairs, Cooperative Studies Program.
A group of current and former Meta employees sued the company Monday after the social media giant reduced its workforce by 10% using an artificial intelligence model to select certain workers.
The 26 unnamed plaintiffs filed the suit in the Northern District of California federal court, claiming Meta began notifying employees on May 20 of a “mass reduction in force” and used an AI system to target workers who took or requested protected leave.
“Meta did not assemble the termination list through the considered judgment of managers who knew the work,” the plaintiffs write in their 71-page complaint. “Instead, Meta used a constellation of internal artificial-intelligence systems — including a system referred to internally as ‘Metamate,’ employee-trained ‘second-brain’ agents, keystroke- and activity-monitoring data, AI-token-usage dashboards, and algorithmically assisted performance ranking and calibration — to score, rank and select employees for inclusion on the list.”
Because the AI used performance ratings, productivity and other output metrics, the plaintiffs say the system, by design, would exclude employees who had taken time away from work and didn’t have as many metrics to measure against other employees.
“The result was that employees who took protected leaves were disproportionately selected for layoff, based on scoring that not only failed to account for their protected leaves, but in effect penalized the employees for exercising their legal rights to these leaves,” the plaintiffs write.
The plaintiffs work in various roles across Meta throughout the U.S., including in California, Florida, Illinois, New York, Pennsylvania and Washington state. They say they share one thing in common: All took, requested or were approved for protected leave within the past 24 months.
Because Meta requires employees to sign a mutual arbitration agreement with a class action waiver, the plaintiffs seek to pursue their claims individually in arbitration. They are asking the court for injunctive relief to stop their terminations and restore their employment status as of May 20. Their claims include violations of state-protected leave laws, the Family and Medical Leave Act, the Pregnancy Discrimination Act and the Americans with Disabilities Act.
In April, Meta announced plans to lay off about 8,000 employees, roughly 10% of its workforce, while “several thousand additional employees would be reassigned to new artificial intelligence initiatives, as Meta sought to remake itself into an ‘A.I.-first’ company,” the plaintiffs say.
Earlier in the year, Meta developed a monitoring program that captured keystrokes, screen content, mouse activity, browser history, messages, emails and voice, video and location data on company-issued devices.
“The data gathered through the employee-tracking program was used to build A.I. tools, including by a new engineering organization to which employees were reassigned on a non-optional basis,” the plaintiffs write.
The plaintiffs say Meta’s deployment of the monitoring program was “announced through a low-visibility internal post — made by an engineer rather than a senior leader, in a secondary group rather than Meta’s official employee-notice channel — with little notice and no consent or click-through acknowledgment; on at least some teams, employees received no consent or acknowledgment prompt at all, and, at least initially, there was no way to opt out.”
U.S. District Judge William Orrick, a Barack Obama appointee, is assigned to the case.
In a statement, a Meta spokesperson said, “These claims lack merit and are not based on facts. Workforce management and organizational decisions were and are made by people, not AI.”
Attorneys representing the plaintiffs did not immediately respond to a request for comment.
https://www.courthousenews.com/meta-employees-sue-over-use-of-ai-in-workforce-reduction/
US President Donald Trump welcomed Iraqi Prime Minister Ali al-Zaidi to the White House on Tuesday for his first foreign trip since taking office. The leaders shook hands ahead of high-stakes talks expected to shift bilateral relations from crisis management to a strategic economic partnership.
This meeting is expected to focus on energy and trade agreements, with Iraq seeking US investment and alternative export hubs to reduce Strait of Hormuz dependency. A proposed energy fund, financed by Iraqi oil exports of up to 2 million bpd, is also on the table as Baghdad aims to boost production to 7 million bpd by 2029.
https://breakingthenews.net/Article/Trump-and-Iraqi-PM-al-Zaidi-greet-at-White-House/66694973
Iran's Kish Island power generation facility sustained damage during a US missile strike on Monday night, according to the facility, as reported by IRNA on Tuesday. The Kish Water and Power Engineering Company reported that a projectile exploded near the plant, altering the technical parameters of several units.
Experts are currently assessing the damage, with results expected in the coming days. Authorities warned that some generators may need to be taken offline for repairs, potentially resulting in scheduled temporary blackouts. Despite the attack, the water and electricity supply remained uninterrupted.
Several vessels in the port area also sustained damage, but no casualties or damage to residential or commercial buildings were reported. The company has urged residents to conserve energy and avoid approaching sensitive areas.
https://breakingthenews.net/Article/Iran's-Kish-power-plant-hit-in-US-attack/66694707
HCA Healthcare lowered its annual profit forecast on Tuesday, weighed by an increase in the number of uninsured patients, primarily of those who lost coverage under the so-called "Obamacare" plans.
Shares of HCA fell nearly 10% in premarket trading.
As subsidies under Affordable Care Act or 'Obamacare' plans expire this year, hospitals like HCA face declining patient volumes for elective surgeries and diagnostics, even as costs increase from providing uncompensated care to more uninsured patients.
https://finance.yahoo.com/healthcare/articles/hca-cuts-annual-profit-forecast-123144619.html
