BackgroundSleep-related problems are common among patients with rheumatoid arthritis (RA) and contribute substantially to disease burden and reduced quality of life. Evidence from the World Health Organization Eastern Mediterranean Region (WHO EMRO) remains fragmented, with variability in reported prevalence, sleep constructs assessed, and associated risk factors. This study aimed to systematically review and meta-analyze the prevalence and correlates of sleep-related problems among adults with RA in WHO EMRO countries.MethodsA systematic search of PubMed, Scopus, Web of Science, Embase, CINAHL, and Google Scholar was conducted to identify observational studies reporting sleep-related outcomes among adults (≥18 years) with RA in WHO EMRO countries from inception to 27 July 2025. Study screening, data extraction, and quality appraisal using Joanna Briggs Institute (JBI) checklists were conducted primarily by a single author, with methodological oversight and consultation from senior collaborators. Eligible studies reported prevalence or sufficient data to calculate prevalence of specific sleep-related constructs, including subjective sleep quality, insomnia symptoms, daytime sleepiness, or obstructive sleep apnea. Random-effects meta-analysis (DerSimonian-Laird) was used to pool prevalence estimates and odds ratios (ORs) for associated risk factors. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Subgroup analyses were conducted by sleep construct, assessment method, and country. Publication bias was evaluated using funnel plots, Egger’s test, and Begg’s test, with cautious interpretation due to the small number of studies.ResultsTen studies met inclusion criteria for qualitative synthesis, and six studies (n = 2,315 participants) were included in the quantitative meta-analysis. The pooled prevalence of sleep-related problems was 60.9% (95% CI: 56.5%–65.2%), with substantial heterogeneity (I² = 88%, p < 0.001), reflecting differences in sleep constructs and assessment methods. Subgroup analyses yielded pooled prevalence estimates of 58% for insomnia symptoms, 65% for obstructive sleep apnea-related measures, and 61% for poor subjective sleep quality (PSQI above cut-off), with no statistically significant differences between subgroups. Among associated factors, depression showed the strongest association with sleep-related problems (OR = 2.65; 95% CI: 1.87–3.75), followed by pain (OR = 2.18; 95% CI: 1.68–2.84), fatigue (OR = 1.91; 95% CI: 1.45–2.52), female gender (OR = 1.67; 95% CI: 1.25–2.23), and older age (OR = 1.42; 95% CI: 1.12–1.80). Heterogeneity for risk factor analyses ranged from low to moderate. Publication bias assessments did not indicate statistically significant small-study effects but were underpowered.ConclusionSleep-related problems—assessed using heterogeneous subjective and objective measures—are highly prevalent among patients with RA in WHO EMRO countries with available data. Given substantial clinical and methodological heterogeneity and the limited number of contributing countries, findings should be interpreted as reflecting overall sleep-related burden rather than the prevalence of a single clinical disorder. Routine screening, multidisciplinary management, and culturally adapted interventions are recommended. Future large-scale, longitudinal studies using standardized diagnostic criteria across a broader range of WHO EMRO countries are needed to strengthen the evidence base.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251109906, identifier CRD420251109906.
The Download: unlocking lithium and controlling Ebola
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
How a new extraction process could unlock the world’s lithium
A new method for extracting lithium could cut costs and emissions from one of the world’s most important materials for EVs and energy storage.
The technique uses a weak acid to dissolve silicate minerals. That frees not only the lithium but also other useful materials, including alumina and silica.
“At scale, we believe this will be the lowest-cost way of sourcing lithium in the world,” says Yet-Ming Chiang, an MIT professor who co-authored a study of the process published yesterday in Science.
Startup Rock Zero is already working to commercialize the research. Read the full story on a new way to unlock the world’s lithium.
—Casey Crownhart
The deadly Ebola outbreak is proving difficult to control
The alert was raised on May 5. Four health-care workers in the Democratic Republic of the Congo had died from an unknown illness within four days. Tests in Kinshasa revealed the culprit: the Bundibugyo virus, one of the causes of Ebola.
A couple of weeks ago, an outbreak of hantavirus erupted aboard a cruise ship. Three people died, but the outbreak was kept under control. The picture for Ebola is bleaker for several reasons, including the disease itself, the available treatments, and the local environment.
Find out why the outbreak is causing alarm.
—Jessica Hamzelou
This story is from The Spark, our weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.
How the Pope’s Magnifica Humanitas offers a template for individuals to meet the AI moment
——Father Séamus Finn, a leader in faith-based and socially responsible investing with the Oblates of Mary Immaculate, and Sister Susan Francois, assistant congregation leader and treasurer of the Sisters of St. Joseph of Peace
Pope Leo XIV’s new encyclical on artificial intelligence includes a statement that warrants serious attention from technologists and policymakers: “Technology is never neutral.”
Magnifica Humanitas is a call to act with courage and solidarity as AI transforms human life, framing the choice ahead as one between the Tower of Babel and the rebuilding of our common humanity. It warns that corporations alone cannot set the direction of such a transformation.
With governments slow to regulate AI, institutional investors are stepping into the gap. Here’s how they can build a better future.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 Anthropic is now valued higher than OpenAI
It hit a $965 billion valuation after a new funding round. (AP News)
+ Claude demand has driven annualized revenue to $47 billion. (WSJ $)
+ The funding round may be Anthropic’s last before an IPO. (TechCrunch)
+ What even is the AI bubble? (MIT Technology Review)
2 A Blue Origin rocket has exploded in a setback to NASA’s Moon plans
New Glenn burst into flames during testing on a Florida launchpad. (CNBC)
+ Blue Origin is heavily involved in NASA’s Moon base plans. (The Verge)
+ It also wants to compete with Elon Musk’s SpaceX. (Reuters $)
3 Adversaries are tracking US troop locations via mobile phone data
The Pentagon has long ignored warnings of this exact threat. (Reuters $)
+ The targeting uses commercially available location data. (Wired $)
+ LLMs could supercharge mass surveillance. (MIT Technology Review)
4 Anthropic plans a broad rollout of Mythos AI in the coming weeks
Despite concerns over its cybersecurity capabilities. (CNET)
+ Claude Opus 4.8 is now out, with a promise to be more honest. (The Verge)
5 Grok oversaw a crime spree in an AI safety test
Models were tasked with governing a simulated society. (Fortune)
+ Grok committed 180 crimes, while Claude ruled with restraint. (Gizmodo)
6 Amazon has scrapped an AI leaderboard after worker gaming
Employees were artificially inflating usage scores. (FT $)
+ We can build better AI benchmarks. (MIT Technology Review)
7 Political spending by AI and crypto groups is shifting elections
They’ve pushed their preferred candidates closer to power. (Axios)
8 China’s tech boom is fueling a new wave of industrial tourism
Visitors are touring AI labs and EV factories. (Rest of World)
9 Alibaba’s MuleRun aims to replicate the OpenClaw craze
The AI agent platform is positioned as a safer alternative. (SCMP)
10 Mysterious changes have emerged in the Sun’s magnetic field
They could reshape space weather forecasts. (404 Media)
Quote of the day
“What Peter Thiel is doing is terrible. His settling in Argentina is even worse.”
—Elisa Lilita Carrió, an Argentine politician, writes on X that Peter Thiel’s relocation to her country has angered her even more than his leadership of Palantir.
One More Thing
NASA, ESA, CSA, STSCI, WEBB ERO PRODUCTION TEAM
How the James Webb Space Telescope broke the universe
When the James Webb Space Telescope began full operations in 2022, astronomers were in awe of the flood of data that arrived.
“Every hour we were looking at a galaxy or an exoplanet or star formation,” says NASA scientist Heidi Hammel. “It was like a firehose.”
Since then, JWST has delivered nonstop discoveries, from distant galaxies to new planetary atmospheres. “We’re cracking open an entirely new window on the universe,” says Hammel.
Discover how JWST has transformed astronomy.
—Jonathan O’Callaghan
We can still have nice things
A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ Kubrick fans will love this Lego recreation of Dr Strangelove.
+ Here’s a fascinating explanation of why seven landlocked countries have navies.
+ This mesmerizing 4K remaster of a super typhoon turns weather data into cinematic art.
+ Go inside the genius of Queen with this track-by-track breakdown of “Bohemian Rhapsody.”
The deadly Ebola outbreak is proving difficult to control
The alert was raised on May 5. Four health-care workers in the Ituri Province of the Democratic Republic of the Congo had died from an unknown illness within four days.
Rapid response teams were sent to investigate, and tests at a research center in Kinshasa revealed the culprit: the Bundibugyo virus, one of the viruses that cause Ebola. Suspected cases of the disease have snowballed in the last few weeks. By May 24, the WHO had estimated that 223 people had died from the disease. There were over 900 suspected cases. Today’s figures are likely to be higher.
A couple of weeks ago, I covered the hantavirus outbreak aboard a cruise ship. Three people sadly died, but the outbreak itself was kept under control. There have been no further deaths, and passengers have been safely repatriated. The picture for Ebola is far bleaker. And there are several reasons why.
The most obvious is the disease itself. Ebola is a severe disease with an average 50% fatality rate. Previous outbreaks have resulted in thousands of deaths. (Hantavirus also has a high fatality rate, but it doesn’t usually spread as easily between humans.)
Between 2014 and 2016, an Ebola outbreak in West Africa caused more than 11,000 deaths. A more recent outbreak, which took place between 2018 and 2020, caused 2,299 deaths before being brought under control with a vaccination campaign.
But those outbreaks were caused by the Zaire virus, which has a different genetic sequence. There is no vaccine for the Bundibugyo virus. We don’t know if the two vaccines approved for Zaire might also work for Bundibugyo. There’s a concern they might even make things worse by interfering with a person’s immune response to the virus.
Scientists are working on potential Bundibugyo vaccines. But the most advanced efforts are still months away from clinical trials. There are no specific antiviral treatments for the virus, either.
So to control the outbreak, health-care workers are trying to stop the spread of the disease. Ebolaviruses can be transmitted to humans by animals including fruit bats, chimpanzees, and gorillas. They can then spread between people via contact with bodily fluids such as blood or vomit.
That’s why the virus is often spread among family members, to health-care workers, and during some burial services. The WHO advises isolating people who have the virus in treatment centers. It also recommends safe burial measures that limit physical contact with the deceased, for example. Communities need to be informed about the virus and how it spreads, and health professionals should be on hand to diagnose cases and track them.
That’s all easier said than done in an era of misinformation. Some members of the community even doubt whether the disease is real. There have been three attacks on health-care facilities in the region in recent weeks.
Last week, two treatment centers were burned down. The first incident occurred after relatives of a deceased man were prohibited from retrieving his (infectious) body. As a result of the second incident, 18 suspected cases reentered the community.
A couple of days later, a group of men unleashed gunfire at Mongbwalu General Hospital, which was also treating people with Ebola. They were demanding the bodies of their deceased relatives.
There are more causes for concern when it comes to the spread of the virus. The Ebola outbreak is thought to have originated in Mongbwalu, a high-traffic mining hub. People who caught the virus in Mongbwalu are thought to have sought care in neighboring districts. And the wider province borders both South Sudan and Uganda. So far, Uganda has reported seven confirmed cases and one death. South Sudan’s health ministry has said it will strengthen surveillance, but no cases have been reported in the country so far.
Violence in the region is making it much harder to contain the spread of the virus, too. Conflict involving multiple armed groups, including deadly attacks on civilians, has hampered humanitarian and health-care efforts. Poor infrastructure and damaged roads make matters even worse. Food insecurity is ravaging the region as well—this year, nearly 10 million people in the region face acute hunger.
Together, these factors are making it “nearly impossible” to isolate people with Ebola and trace others who have been in contact with them, WHO director general Tedros Adhanom Ghebreyesus said in a statement earlier this week.
The dismantling of US aid programs hasn’t helped either. US government funding for international health projects has steeply declined since the start of President Donald Trump’s second term. These cuts have harmed disease surveillance systems, according to the International Rescue Committee, a humanitarian nonprofit.
“Funding cuts have left the region dangerously exposed,” Heather Reoch Kerr, the organization’s country director for the Democratic Republic of the Congo, said in a statement. “Years of underinvestment and recent funding cuts have left many health facilities without adequate protective equipment, surveillance capacity, or frontline support needed to respond quickly and safely.”
The US has mobilized emergency funding for the outbreak, and a spokesperson for the State Department has argued that none of the administration’s actions have hampered the Ebola response. But health experts counter that the damage has already been done.
On May 17, the WHO declared the Ebola outbreak a public health emergency of international concern. In a statement on Wednesday, Tedros described the situation as “a catastrophic collision of disease and conflict with the Ebola outbreak in Ituri province outpacing the response.”In an online appeal to residents on Wednesday, ahead of an in-person visit, Tedros pleaded for a ceasefire and commended the spirit of community members. He also acknowledged the steep challenges they face. “You are already carrying so much: malaria, hunger, insecurity, and the daily struggle to keep your families safe,” he wrote in French. “And now Ebola. It’s not fair, and I won’t pretend otherwise.”
This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.
STAT+: The woman behind the world’s biggest longevity competition
BERKELEY, Calif. — Jamie Justice is an anti-aging researcher with a name fit for a superhero and a grand mission to match. A few years ago, she left her tenure-track job at Wake Forest University to team up with entrepreneur Peter Diamandis on XPRIZE Healthspan — a $101 million global competition meant to identify therapeutic treatments that can restore muscle, cognition, and immune function in older adults.
“There’s a booming market for slowing aging, but there’s no way to tell if [treatments] work,” Justice said onstage at the longevity conference Vitalist Bay here this month. XPRIZE Healthspan, for which she serves as executive director, was created to bridge that gap. The 10 teams selected from a pool of 40 this year will be required to test out their therapies in yearlong randomized controlled clinical trials before the winner of the grand prize is announced in 2030.
Dressed in wide-legged jeans and a dark blazer, Justice walked the audience through XPRIZE competitors’ varying approaches to longevity. Exercise, senolytics (drugs that target damaged “zombie” cells that increase as we age), and personalized medicine geared toward biomarkers were among some of the prevailing approaches.
The longevity field, as the people involved in it acknowledge, tends to attract colorful characters with far-out theories. (A man in a purple cape trotted regally through the grounds of Vitalist Bay.) Figures like Justice, who’s hung onto her academic ties as an adjunct assistant professor of gerontology and geriatric medicine at Wake Forest, occupy a more grounded, science-based part of the spectrum. But she welcomes a big-tent approach to the world of anti-aging research. “I think, as scientists, we have to be really mindful to not turn into gatekeepers,” she told STAT during an interview after her talk.
STAT sat down with Justice to learn more about the XPRIZE Healthspan competitors, research on what people really want in their old age, and the problem of “purely scammy” companies giving longevity a bad name.
A Study of the Feasibility, Safety and Tolerability of Aticaprant as Adjunctive Treatment in Participants With Schizophrenia
Conditions: Schizophrenia
Interventions: Drug: Aticaprant; Drug: Placebo
Sponsors: Janssen Research & Development, LLC
Recruiting
Interventions: Drug: Aticaprant; Drug: Placebo
Sponsors: Janssen Research & Development, LLC
Recruiting
Pilot Feasibility Study With Doulas
Conditions: Post Partum; Maternal Depression; Maternal Depression and Parent Practices, Postpartum
Interventions: Behavioral: YouMatter
Sponsors: Duke University
Not yet recruiting
Interventions: Behavioral: YouMatter
Sponsors: Duke University
Not yet recruiting
Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study
Conditions: Post-Traumatic Stress Disorder
Interventions: Device: Continuous wearable physiological monitoring (EmbracePlus, Empatica); Drug: Ketamine-assisted therapy (independently arranged); Other: Structured pre- and post-session interviews
Sponsors: Adriaan Dirk van der Wart
Not yet recruiting
Interventions: Device: Continuous wearable physiological monitoring (EmbracePlus, Empatica); Drug: Ketamine-assisted therapy (independently arranged); Other: Structured pre- and post-session interviews
Sponsors: Adriaan Dirk van der Wart
Not yet recruiting
Detecting Alzheimer’s Early by Brain Scan or Blood
While Alzheimer’s disease accounts for about 60-70% of dementia diagnoses, the timing of these diagnoses occur late in disease progression. Identifying early signs of Alzheimer’s may allow individuals time to address potential risk factors in their lives.
“Alzheimer’s disease pathology begins years before symptoms emerge,” said Kristine Yaffe, MD, vice chair in the UCSF Department of Psychiatry and Behavioral Sciences. Yaffe and her team have spent years researching modifiable risk factors that may play a role in dementia development, including physical and cognitive activity, depression, smoking, and cardiovascular health.
A current trajectory of research into Alzheimer’s disease is focusing on ways to detect the disease early, before major symptoms manifest. Two new studies published in The Lancet present different methods for detecting Alzheimer’s disease that converge in their early detection ability.
Alzheimer’s disease is characterized by increased amounts of tau and amyloid-β plaques. Growing research indicates the importance of tau pathology and amyloid-β accumulation at initiating changes to the brain associated with Alzheimer’s disease.
“Tau is the biology most closely tied to symptoms and future decline,” said Tharick Pascoal, MD, PhD, associate professor of psychiatry and neurology at the University of Pittsburgh and a behavioral neurologist at University of Pittsburgh School of Medicine. “If we can detect tau earlier and stage it more precisely, we can make better decisions about who is truly on an Alzheimer’s trajectory, which matters for clinical trials now and could shape clinical decision-making as new therapies emerge.”
Researchers at the University of Pittsburgh led by Guilherme Povala, PhD, and Bruna Bellaver, PhD, have focused their work on brain scan imaging to detect tau both more effectively, and earlier.
The team’s recently published work compared the ability of two tracers used in non-invasive PET scans to visualize Alzheimer’s-associated tangles of tau protein. To do this, participants underwent paired tau PET scans, the first using a standard tau tracer, Flortaucipir, or a new tracer, MK6240. Within 45 days of the PET scan, participants also received an amyloid-β PET scan and detailed cognitive assessments. Of the 775 initial participants, 682 completed all of the study components.
“Because participants received both tracer scans within a short window, we’re looking at the same moment in the disease course, so differences we see reflect the tracers, not changes over time,” explained co-lead author, Guilherme Povala, PhD, postdoctoral associate at the University of Pittsburgh, about the experimental design.
Analysis showed that imaging with the MK6240 tracer detected more tau than tracing with Flortaucipir. In participants with cognitive impairment and positive amyloid-β results, MK6240 identified move than twice as many tau-positive cases, 15% compared with six percent, which was an additional 23 patients per 100. Tracing with MK6240 also identified increased tau, 28% vs. 16% with Flortaucipir, in patients with mild cognitive impairment and dementia, resulting in 15 or 21 additional cases per 100 participants scanned.
“People typically seek evaluation because they have memory concerns or other symptoms,” pointed out co-lead author, Bruna Bellaver, PhD, research assistant professor of psychiatry at the University of Pittsburgh. “Tau PET is one tool that can help clinicians stage disease biology and make more informed decisions.”
Across the country in California, researchers from University of California, San Francisco, have drawn on their experience with blood biomarkers in an effort to develop a method for detecting Alzheimer’s before major symptoms develop.
The west coast study included 1,350 participants (out of an initial 2248) who were retained in the U.S. Coronary Artery Risk Development in Young Adults (CARDIA) study. Participant blood plasma was tested from samples that were collected at project year 35 (2020-2022) and five years prior. Plasma biomarkers for amyloid-β (Aβ42 and Aβ40) and tau (p-tau217) were measured and used to calculate p-tau217-to-Aβ42 and Aβ42-to-Aβ40 ratios and then those were compared to the cognitive assessment scores that were measured at the same time period. Any participants missing materials were excluded from the initial cohort. During analysis, participants were also classified by Alzheimer’s disease neuropathy status of negative, intermediate and positive based on amyloid PET-validated cutpoints for each marker.
Results from the initial analysis showed that participants with high biomarkers also had both lower processing speeds and lower executive function in the first time point. After five years, the group that initially had high levels of biomarkers now had a 2.5 to 4 times increased risk of rapid decline in verbal memory, and three to four times the risk for rapid decline in processing speed. Together, these data suggest a connection between the observed cognitive decline and increase in biomarkers.
While brain scans, and spinal fluid tests are often used and widely available, blood tests are less invasive and relatively inexpensive, potentially enabling more patients access to diagnostics along with early detection prior to symptom development. While there is potential for measuring blood biomarkers for clinical use, senior author, Yaffe, prescribes cautious optimism. “There’s a possibility of false positives and [these markers] can only be used for Alzheimer’s, not other dementias, meaning about 60% to 70% of all dementia cases,” she said. “But for some people who discover they have the biomarkers, testing could open a window to embark on interventions that may postpone Alzheimer’s onset.” More work is still needed to clarify the utility of both early detection methods in the clinic.
Overall, both studies show significant progress in developing strategies to identify dementia, and specifically Alzheimer’s disease, earlier. Earlier diagnosis may lead to earlier intervention and potentially more positive outcomes for patients. As Yaffee concluded, “Detecting the disease early means patients can target modifiable risk factors and maybe seek other care.”
The post Detecting Alzheimer’s Early by Brain Scan or Blood appeared first on Inside Precision Medicine.
Antibody Drug Slows Disability Progression in Advanced Multiple Sclerosis
Results from the Phase III ORATORIO-HAND study show that ocrelizumab, an antibody drug already prescribed to some patients with multiple sclerosis (MS), could benefit a much larger patient population, including those who are older or at more advanced stages of the disease. Published today in The Lancet, these findings could change the way clinicians understand and manage MS.
“Our study suggests we should think differently about what successful treatment looks like in advanced MS and that we shouldn’t assume a lack of benefit in certain groups,” said Gavin Giovannoni, MD, PhD, professor of neurology at Queen Mary University of London. “These findings show that treatment can make a meaningful difference to people with more advanced forms of MS and can help preserve hand and arm function, which is important for maintaining independence, daily activities and quality of life.”
The clinical trial recruited over 1,000 patients with primary progressive multiple sclerosis (PPMS), a form of MS where disability worsens over time that affects about 10–15% of people diagnosed with the autoimmune condition. Ocrelizumab is currently available to patients early on in their PPMS with lower levels of disability, delivered as an infusion every six months to reduce disability progression. However, those with advanced disease, including patients who need a wheelchair to move around, are not eligible for this treatment and currently have limited options available to them.
Compared to a placebo, ocrelizumab significantly reduced the risk of disability progression by 30%, with stronger effects in patients showing signs of inflammatory activity on MRI scans, for whom the drug reduced this risk by 55%. The treatment also reduced the worsening of hand and arm function by 41% after 12 weeks and lowered the need for a wheelchair by 52% among patients who were already unable to walk freely at the start.
These results settle a longstanding debate over whether more advanced forms of multiple sclerosis can still benefit from treatment. In contrast with previous studies, which often excluded patients over 55 and those with advanced disability, this clinical trial recruited participants up to 65 years old and those with substantial mobility impairment.
In addition to assessing walking ability, the study focused on assessing hand and arm function. This decision was based on a separate survey conducted by Giovannoni’s team in which patients with worsening multiple sclerosis reported prioritizing upper-limb function due to its importance for their independence, including their ability for cleaning and grooming themselves.
“MS can be debilitating, exhausting and unpredictable, and hand and arm function is essential for helping people to remain independent,” said Catherine Godbold, PhD, senior research communications manager at the MS Society. “Many previous trials have focused solely on walking ability as a measure of whether a drug is effective. But trials like this are vital in helping us find treatments for everyone.”
“Ocrelizumab is already used as a treatment for active relapsing MS and early primary progressive MS,” she added. “These results could mean it is made available for more people with primary progressive MS, who don’t currently have access to any treatment options. The key now is how we work together to see these findings translated into clinical practice.”
The post Antibody Drug Slows Disability Progression in Advanced Multiple Sclerosis appeared first on Inside Precision Medicine.
BrainBaseline Assessment of Cognition and Everyday Functioning (“BRACE”-ing for the Future): Establishing iPad-Based Norms for Cognitive Function in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study Combined Cohort Study
Background: Digital cognitive assessments are increasingly used in large-scale studies to assess brain health, offering scalable, standardized, and self-directed testing solutions. Cognitive function remains a concern for people with HIV despite antiretroviral therapy. The BRACE (BrainBaseline Assessment of Cognition and Everyday Functioning) is a validated tablet-based screener for cognition in people with HIV. Preliminary pilot norms were established in a small sample (n=144), but full regression-based normative data have not yet been developed. Consequently, HIV serostatus differences based on standardized BRACE scores and cognitive correlates have not been systematically examined. Objective: This study aims to develop regression-based normative data for BRACE performance in people without HIV who were demographically and behaviorally comparable to people with HIV within biological sex; to examine differences in cognitive performance by HIV status and biological sex; and to evaluate sociodemographic, behavioral, and clinical correlates of BRACE performance. Methods: A total of 2937 participants (1063 people without HIV [499 women] and 1874 people with HIV [1053 women]) in the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study completed BRACE once between November 2020 and March 2025. BRACE includes the Trail Making Test (A and B), Stroop-Color, and visual spatial learning. Regression-based norms were derived from people without HIV using multiple demographic models (eg, age-only, age + education, and age + education + sex). The age + education model was selected for primary analyses because it provided the best balance of interpretability, parsimony, and generalizability while avoiding race-based corrections. HIV serostatus and sex differences were examined using ANOVA and tests, with effect sizes calculated using Cohen’s . Results: Cognitive performance was largely comparable between people with HIV and people without HIV across all BRACE outcome measures. Statistically significant differences were very small in magnitude (all effect sizes<0.11) and primarily observed among men on Stroop-Color. Across groups, older age and fewer years of education were associated with poorer raw BRACE performance, although these associations attenuated after demographic adjustment using T-scores. Most clinical and behavioral factors (eg, hypertension, smoking, and noncannabis substance use) were related to poorer raw scores but not standardized performance. However, diabetes and cannabis use remained independently associated with T-scores across multiple measures—diabetes with poorer scores and cannabis use with higher scores, an association that should be interpreted cautiously. HIV-specific clinical factors, such as nadir CD4 count and antiretroviral therapy duration, were linked primarily to raw scores. Conclusions: This study establishes the first regression-based normative data for BRACE, derived from a large, demographically diverse people without HIV, and demonstrates its applicability for evaluating cognitive function in people with HIV. Findings indicate minimal cognitive differences between people with HIV and people without HIV and highlight the influence of common sociodemographic and metabolic factors. These results support BRACE as a scalable, reliable, and self-administered digital tool for assessing cognitive health in diverse populations and underscore its potential for longitudinal monitoring and precision phenotyping in both research and clinical contexts.
