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Interdisciplinary report illuminates demographic, systemic health factors of dry eye disease
Dry eye disease was more prevalent in women than men, and was found to increase with age, investigators reported. Image credit: ©Rido – stock.adobe.com
The Tear Film and Ocular Surface Society (TFOS) DEWS III Digest Report, published in June 2025 in American Journal of Ophthalmology, has identified key research published since the 2017 TFOS DEWS II Workshop reports in the form of sex, gender and hormones; epidemiology; pathophysiology; tear film; pain and sensation; iatrogenic; and clinical trial design.1 The report was comprised in an effort to support evidence cited in the TFOS DEWS III Diagnostic Methodology and Management and Therapy reports, and included input from 80 experts in 18 countries, according to TFOS.2
Study authors, led by Fiona Stapleton, PhD, MSc, of the School of Optometry and Vision Science, UNSW Sydney in NSW, Australia, outlined advancements in tear film research, a clarification of pathophysiological distinctions between aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE) and ocular pain perception, among others.1
For sex, gender and hormones, study authors focused on studies published after July 1, 2017 and cited significant sex-related differences in the lacrimal gland, meibomian gland, cornea, eye lid blinking, corneal thickness, sensitivity, re-epithelisation, pain assessment, hormonal regulation of the ocular surface and adnexa and dry eye disease (DED)-induced damage, among others.1
“There have been significant research advances linking sex, hormones and gender to DED. Aging, cancer and hormone therapy increasingly broaden the interdisciplinarity in this field over time,” the report authors stated. “Despite the significant impact of gender-affirming hormone therapy on the entire endocrine system and its effects on physical and mental health, there is limited information on its impact on ocular health. Variations in age, health profile, gender-affirming hormone therapy compliance and barriers to accessing regular healthcare limit the documentation of side effects. Clinicians and future research should consider these variations, as recommended in a recent systematic review on the medical aspects of the transgender and gender diverse population.”
For epidemiology, DED was found to increase with age and was more common in women than men; signs and symptoms were more common in women with higher rates in younger and older adults. Some of the outstanding questions that remain from the research are issues concerning disease severity, geographic considerations, the generalisability of prevalence measures for DED in children and adults under 40 years of age and a need for appropriately powered studies to determine risk factors in patients under 40. Researchers noted that a limited number of studies exist that explore the prevalence, risk factors, or natural history by disease severity.1
Opportunities for future research concerning tear film were identified in the needed exploration of the relationship between disordered lipids that result in spreading and increased elasticity as compared to ordered lipids that lead to improved resistance to evaporation. Researchers also called for a more detailed understanding of whether tear biomarkers can be used to differentiate subtypes of DED and referenced the society’s recent Diagnostic Methodology report.1
“Analyses of microbiome changes across individuals of different ethnicities and countries of residence may provide further insights into its potential role in DED pathogenesis or as a marker for the disease,” the study authors noted. “Understanding the potential role of different microRNAs in DED pathogenesis, DED subtype or as biomarkers could be a highly promising area for future investigation.”
Recommendations for DED management were also suggested by the study authors under iatrogenic, particularly regarding DED implicated in a variety of anti-glaucoma topical drugs, preservatives and excipients, antibiotics and hormone replacement therapy, among others.1
“The first step is to investigate which medication is causing DED and try to stop its use. This subtraction can be challenging when discontinuing the treatment, which presents a risk to the eye’s health,” the study authors noted. “Sometimes, multiple drugs and components are involved, or adverse effects appear long after treatment initiation, making identification of which is causing DED even more difficult.”
References:
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Stapleton F, Argüeso P, Asbell P, et al. TFOS DEWS III Digest Report. Am Journ of Opthalmol. 2025. https://doi.org/10.1016/j.ajo.2025.05.040
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TFOS dry eye workshop (DEWS) III: completed! Tear Film and Ocular Surface Society. News release. June 10, 2025. Accessed June 18, 2025. https://www.tearfilm.org/dettnews-tfos_dry_eye_workshop_dews_iii_completed/7450_16/eng/
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VCs Are Turning Away From The ‘fixer-Upper’ Founder
Faster. Better. Smarter. Smoother.
What might sound like a Daft Punk lyric has become something of an anthem for tech startups. In recent years, a strong proportion of the pitches I’ve reviewed have been for startup ideas focused on incremental gains. Think faster versions of existing tools, smoother, more interoperable systems, and any other kind of upgrade ending in “-er”.
Of course, aiming for better is no bad thing. By improving on great ideas, we can drive progress and develop more tailored solutions. And there have been brilliant, highly successful businesses that have emerged as a result of this philosophy: zoning in on a need and applying tech or better design to make it more efficient, effective or enjoyable.
But, as I covered in my recent piece on moat building, the rise of vibe coding and open-source AI means being the ‘best version right now’ is no longer defensible as a long-term strategy. Betting on being the next best upgrade is a losing game. It leaves your offering just one fix or disrupter away from being replaced.
Computer service and assistance concept with work tool icon on a laptop keyboard 3D illustration.
That’s why VCs like me are turning away from “incremental improvers” in favour of paradigm-shifting experiences; startups who are building something genuinely novel with a user experience that’s 5 or even 10 times better. So if you’re a founder hoping to attract investment, here are three things you can do to demonstrate that you’re more than a fixer-upper.
1. Disrupt, don’t decorate
The idea that ‘disruptors’ have the greatest potential for long-term impact is nothing new. But now, in a market increasingly saturated by ‘add-on’ technology, it’s more important than ever that founders distinguish themselves from what’s already out there.
That means daring to imagine where technology is heading, not just where it is today. Startups able to do this have a much greater shot at reaching and dominating untapped markets. Revolut’s $48 billion valuation and Airbnb’s $11bn annual revenue didn’t come from minor upgrades or applying a bit of polish around the edges. They’re the achievements of founders who believed that things could be done differently to deliver a customer experience that was unlike anything else. And then built platforms that made it a reality.
Perhaps you’re disrupting an industry because you’ve lived its challenges first-hand. This was the case for Molly Johnson-Jones, who co-founded Flexa (an Ada portfolio company) after being fired for asking to work from home while managing a chronic health condition. Today, millions of people use the platform to access transparent, verified information on different working environments and cultures, so candidates can find roles that actually work for them. With no predecessor and no playbook, Flexa has carved out a category of its own and become indispensable to modern jobseekers.
Or maybe you’re introducing much-needed digital solutions to fix an age-old analogue problem. Take Patchwork Health for example. Founded by two NHS doctors who were frustrated by the relentless pressure and lack of flexibility on the frontline, their digital workforce management tools are making sustainable staffing a reality in healthcare. Patchwork’s tech-led approach includes an app which lets clinicians book shifts, request holiday and manage their own schedules all in one place. Meanwhile, managers can view staffing trends and fill vacancies through the same platform. This isn’t just an upgrade, it’s a huge step in modernising a process that’s long been held back by archaic systems, siloed data and painstaking admin.
So if you find yourself saying ‘we’re the next [insert successful company],’ it’s worth asking: am I a disruptor, or merely a decorator neatly papering over cracks?
2. Uncover, then unlock
Fixer-upper founders jostle for space in a market. Real disruptors prise open the doors to places no one has set foot yet. They identify the unmet needs that have existed for so long that everyone else has just taken them for granted. And then they set about solving them.
A great example of this in action is Valla (an Ada portfolio company). Their AI-powered legal tech platform empowers workers embroiled in employment law disputes to access advice. An estimated 12.4 million employees are affected by employment law breaches each year. By bringing down costs and democratising access to support, Valla are unlocking a vast, overlooked user base with huge potential for growth. They’re truly offering a type of service that simply doesn’t exist anywhere else today.
Another example, also in the legaltech space, is Orbital. Through machine learning and AI, their platform streamlines the dense, paperwork-heavy processes of property due diligence, giving lawyers an instant view of the risks and red flags buried in leases and deeds. They’re not competing with innovations from last year – or even from this century. Instead, they’re transforming processes that date back to the Victorian era.
This is what investors like me are after: solutions to long-written-off problems, not face-lifts for challenges that have largely been addressed.
3. Think far, not fast
Disruption is not a product, it’s a process. It requires a continued commitment to uncover new market opportunities and develop new solutions for consumers. There is perhaps no greater example of this than the stratospheric rise of Netflix. What began almost 30 years ago as an innovative new model for DVD rentals is now the world’s largest streaming platform; an entertainment behemoth constantly improving to stay ahead of the competition.
Netflix’s dominance isn’t just the result of one good idea, or one small improvement to existing services, it’s a testament to their ability to look ahead. Instead of stopping at streaming (or indeed at rental by post!), Netflix has continued to lead the market with award-winning original content and unique in-app features. The lesson for founders here is clear: success requires you to champion a business model and a mindset that embraces change.
Of course, startups will always need to tinker with existing products and make tweaks to improve their offering. But this shouldn’t come at the expense of thinking big. This is where initiatives such as Google’s famous ‘20% time’ policy can be helpful; encouraging teams to regularly focus their efforts on more future-gazing projects, and proving to investors that you’re serious about driving impact.
Fixer-upper founders are stuck in the here and now. They admirably take on the pain points of today, but offer little inspiration for tomorrow. True disruptors don’t just muscle their way into new markets; they create new categories, cater to unmet needs, and put the work in to stay on top. If we’re to address some of society’s biggest challenges, we need more innovators and fewer renovators. And investors have their eyes trained on the difference.
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Owners of collapsed oil refinery Prax Lindsey took £11.5m in pay and dividends | Corporate governance
The married couple behind the Prax Lindsey oil refinery awarded themselves at least $15.9m (£11.5m) in pay and dividends in the years leading up to its collapse, it has emerged, as the government urged the company’s boss to “put his hand in his pockets” to help workers.
Winston Soosaipillai, who goes by his middle names Sanjeev Kumar, jointly owned the refinery with his wife, Arani, until it plunged into insolvency on Monday.
The failure of the refinery, which is one of only five left in the UK, has put 625 workers at risk and raised fears about disruption to supplies of customers such as petrol retailers and Heathrow airport.
The sudden demise of the company, which Westminster sources said had assured ministers of its health just weeks ago, prompted the government to order an investigation into “the conduct of the directors”.
Sanjeev Kumar Soosaipillai is the sole director of both the refinery operation and its parent company, according to the latest available filings from Companies House.
The scale of rewards on offer to Soosaipillai and his wife, who is the group’s human resources director, are revealed in a series of annual reports and Companies House filings.
The group paid a dividend of $5.2m to its shareholders in 2024, on top of a $2.1m payment in 2022, the documents show.
The Soosaipillais own 80% of the group directly and 20% via family trusts, indicating that they have extracted $7.3m in dividends since buying the plant from French oil company Total in 2021.
Pay disclosures also reveal the sums paid to the group’s highest-paid director, understood to be Soosaipillai, given that he is the only director.
The pay deals were worth a combined $8.5m between 2022 and 2024, the only years for which accounts have been filed.
In total, the Soosaipillais appear to have handed themselves £11.5m in pay and dividends since buying the refinery in 2021.
Details of the payouts emerged after Mark Shanks, a junior minister in the energy department, called for Soosaipillai to help fund compensation for some of the 625 workers affected by the collapse.
Speaking in the House of Commons on Monday, Shanks said that the government “expect[s] the owners to put their hands in their pockets and provide the support that those workers deserve”.
The division that houses the facility, Prax Lindsey Oil Refinery Ltd, has lost £109m over the same period, although this is not uncommon in large oil and gas operations, whose trading divisions often make up the difference.
Accounts also show that Prax was forced to revise the accounting treatment of one proposed dividend payment, after discovering it did not have enough cash to fund the payout.
During 2023, the Prax Group holding company declared and paid a dividend of $4.98m to its shareholders, the Soosaipillais.
These were paid “in good faith”, according to filings at Companies House, but the company later discovered that the payout “exceeded the available level of distributable reserves”.
The sum was reclassified as an amount owed to the group by “related parties”.
After the year end, a new dividend was declared, which accounts said would be satisfied by releasing the parent company from its obligation to repay sums already transferred.
The Guardian approached representatives of Prax, including one who has previously answered questions on behalf of the Soosaipillais, for comment.
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Vanguard Squads, Assemble! Mecha BREAK Is Available Now – Business Wire
- Vanguard Squads, Assemble! Mecha BREAK Is Available Now Business Wire
- Mecha BREAK: All Platforms, Release Date, System Requirements Sports Illustrated
- Free-to-play mech brawler Mecha Break has attracted 50,000 players within 10 minutes of launching, proving our appetite for giant robots remains insatiable PC Gamer
- Millions of players are waiting: One of the year’s most anticipated free-to-play shooters launches this week Notebookcheck
- Kris Kwok On ‘Mecha Break’ And His Team’s Enduring Love Of Mecha Forbes
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Gold price in Philippines: Rates on July 2
Gold prices remained broadly unchanged in Philippines on Wednesday, according to data compiled by FXStreet.
The price for Gold stood at 6,050.44 Philippine Pesos (PHP) per gram, broadly stable compared with the PHP 6,045.77 it cost on Tuesday.
The price for Gold was broadly steady at PHP 70,571.20 per tola from PHP 70,516.70 per tola a day earlier.
Unit measure Gold Price in PHP 1 Gram 6,050.44 10 Grams 60,504.44 Tola 70,571.20 Troy Ounce 188,190.00
FXStreet calculates Gold prices in Philippines by adapting international prices (USD/PHP)
to the local currency and measurement units. Prices are updated daily based on the market rates taken at the time of
publication. Prices are just for reference and local rates could diverge slightly.
Gold FAQs
Gold has played a key role in human’s history as it has been widely used as a store of value and medium of exchange. Currently, apart from its shine and usage for jewelry, the precious metal is widely seen as a safe-haven asset, meaning that it is considered a good investment during turbulent times. Gold is also widely seen as a hedge against inflation and against depreciating currencies as it doesn’t rely on any specific issuer or government.
Central banks are the biggest Gold holders. In their aim to support their currencies in turbulent times, central banks tend to diversify their reserves and buy Gold to improve the perceived strength of the economy and the currency. High Gold reserves can be a source of trust for a country’s solvency. Central banks added 1,136 tonnes of Gold worth around $70 billion to their reserves in 2022, according to data from the World Gold Council. This is the highest yearly purchase since records began. Central banks from emerging economies such as China, India and Turkey are quickly increasing their Gold reserves.
Gold has an inverse correlation with the US Dollar and US Treasuries, which are both major reserve and safe-haven assets. When the Dollar depreciates, Gold tends to rise, enabling investors and central banks to diversify their assets in turbulent times. Gold is also inversely correlated with risk assets. A rally in the stock market tends to weaken Gold price, while sell-offs in riskier markets tend to favor the precious metal.
The price can move due to a wide range of factors. Geopolitical instability or fears of a deep recession can quickly make Gold price escalate due to its safe-haven status. As a yield-less asset, Gold tends to rise with lower interest rates, while higher cost of money usually weighs down on the yellow metal. Still, most moves depend on how the US Dollar (USD) behaves as the asset is priced in dollars (XAU/USD). A strong Dollar tends to keep the price of Gold controlled, whereas a weaker Dollar is likely to push Gold prices up.
(An automation tool was used in creating this post.)
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Two Holidays Announced in Sindh – ProPakistani
- Two Holidays Announced in Sindh ProPakistani
- Sindh announces public holidays for Ashura Abb Takk News
- Sindh seeks suspension of cellular services on 10th Muharram Geo.tv
- Will govt suspend mobile phone service on Youm-e-Ashur 2025? Pakistan Observer
- Muharram 2025: Mobile, Internet Services to remain suspended in parts of Karachi, Sindh dailyindependent.com.pk
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The relationship between grip strength, 6 minute walking distance and working memory in older adults with mild cognitive impairment: an fNIRS study | BMC Geriatrics
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Proteas thump Zimbabwe to secure 328-run win in Zimbabwe Test
BULAWAYO: South Africa bagged a convincing win 328-run win in the first Test against Zimbabwe after debutant Lhuan-dre Pretorius scored a record-breaking century with Corbin Bosch’s also pitching in via his all-round performance in the first fixture of the two match series.
Chasing a daunting 537-run target, the home side’s batting unit unfolded on a meagre 208 runs.
Zimbabwe resumed their pursuit from 32-1 through opener Prince Masvaure and Nick Welch (0) and got off to a worst possible start as Bosch dismissed the number three batter on the first delivery of the day.
First-innings centurion Sean Williams then joined Masvaure for a brief 32-run partnership after the early blow.
Williams dominated the stand by scoring a quickfire 26 off 18 deliveries before Bosch got him caught behind.
Zimbabwe then lost three more wickets in quick succession and consequently slipped to 82-6, needing a further 455 runs.
Following the slump, skipper Craig Ervine and Wellington Masakadza attempted to launch a recovery by putting together 83 runs for the sixth wicket.
Momentum-filled Bosch broke the crucial partnership by getting rid of Ervine, who scored 49 off 77 deliveries, laced with seven boundaries.
Masakadza, on the other hand, was involved in a meagre eight-run partnership with Vincent Masekesa (3) before being ultimately removed by Codi Yusuf.
He remained the top scorer for Zimbabwe in the run chase with 57 off 92 deliveries, featuring nine boundaries.
Zimbabwe’s number 10 Blessing Muzarabani was the other notable run-getter as he remained unbeaten with a gutsy 32 off 29 deliveries, comprising four fours and two sixes.
Bosch was the standout bowler for South Africa in the second innings, taking five wickets for 43 runs in 12 overs, followed by Yusuf with three, while Keshav Maharaj and Dewald Brevis made one scalp apiece.
For the unversed, debutant wicketkeeper batter Lhuan-dre Pretorius was adjudged the Player of the Match for his monumental 153 in the first innings, which helped South Africa pile 418-9.
In response, Zimbabwe could muster 251 despite a valiant century from Williams as Wiaan Mulder’s four-wicket haul dismantled their batting unit.
Mulder then showcased his batting prowess in the second innings and scored an anchoring century at number three, which was pivotal in helping South Africa to set a mammoth total.
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Association between the American heart association’s life’s essential 8 score and cognitive function: a cross-sectional NHANES study | BMC Geriatrics
Study population
This cross-sectional study recruited participants from NHANES 2011–2012 and 2013–2014 (https://www.cdc.gov/nchs/nhanes/index.htm). NHANES is a public health survey program conducted by National Center for Health Statistics (NCHS) in America. The NHANES project recruits participants using a complex, multistage probabilistic sampling design in two-year cycles. NHANES collects information from questionnaires at home, physical and laboratory examinations in mobile examination center (MEC) and telephone interviews. In this study, samples from NHANES 2011–2012 and 2013–2014 were obtained and combined because NHANES project provided the outcome of several cognitive test in these two cycles specifically. There were totally 19,931 participants in these two cycles. Our study implemented a three-stage exclusion protocol: (1) Primary exclusion of 16,530 participants based on age criterion (< 60 years), (2) subsequent removal of 478 cases with incomplete cognitive assessments or missing subjective cognitive questionnaires, followed by (3) elimination of 1,947 individuals lacking essential metrics for LE8 calculation. Finally, we get 976 eligible participants. (Supplement Fig. 5)
Measurement of LE8 score
LE8 scoring system is comprised of 8 metrics including 4 behavioral metrics (diet, physical activity frequency and duration, nicotine exposure and sleeping) and 4 biological metrics (blood lipids, blood glucose, blood pressure and BMI score) (Supplement Table 1) [7]. Total LE8 score is the average score of above 8 metrics which range from 0 to 100 with higher score indicate healthier cardiovascular condition. In our study, LE8 score was further classified by quartile into 4 groups named Q1, Q2, Q3 and Q4 with Q1 as reference category.
Table 1 Baseline characteristic of covariables according to LE8 score quartile Of the 8 metrics, diet score was assessed according to Healthy Eating Index 2015 (HEI-2015). NHANES collects dietary data with two 24-hour recalls interviews, one is conducted in person in MEC while the other is on telephone several days later. Researchers are able to calculate the dietary intake of participants by combining 24-hour food intake files from NHANES and food patterns equivalents data from United States Department of Agriculture (USDA) (https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/food-surveys-research-group/docs/fped-data-tables/). HEI score includes 13 components of 2 classifications: 9 adequacy components and 4 moderation components. Scoring of dietary components is based on energy density which represents the amount of food components per 1000kcal (Supplement Table 2). Self-report questionnaires from NHANES provides information about physical activity intensity, cigarette smoking behaviors, sleeping duration, diabetes history and medication usage. As for the data of BMI, blood pressure, blood lipid and hemoglobin A1c, blood samples are obtained in MEC and then processed, stored, and transported to laboratories for test. The height and weight used to calculate BMI were measured in the MCE. The full test includes three measurements of both systolic and diastolic blood pressure. When data from all three measurements were available, the average systolic and diastolic blood pressure were calculated. If the full set of three measurements was not available, the average was computed using as many measurements as were available.
Table 2 Weighted coefficients and confidence interval of LE8 score for cognitive test score Measurement of cognitive test score and subjective cognitive performance
NHANES conducted three widely utilized [11,12,13] cognitive tests for participants aged > 60 years in the cycle of 2011–2012 and 2013–2014. First, the word learning and recall modules from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD test) was conducted to assess immediate and delayed learning ability for new verbal information. The test comprises three sequential learning trials followed by delayed recall. During each trial, participants verbally articulate 10 randomly ordered unrelated words presented sequentially, followed by immediate free recall, with word sequence randomization repeated across trials to minimize order effects. A maximum score of 10 per trial is attainable based on correct item retrieval. Second, the Animal Fluency test (AFT) was performed for assessing the executive function where participants are asked to name as many animals as possible in one minute and one point is given for each named animal. Third, Digit Symbol Substitution test (DSST) was conducted which depend on the rapid processing of information, maintaining attention, and retrieving working memory. Participants are provided with a paper which contains 9 numbers with paired symbols, then they are asked to fulfill 133 boxes nearby the numbers with corresponding symbols as much as possible in 2 min. One point is given for one correct match. In this study, we calculated z-score [(individual test score – mean)/standard deviation] of immediate CERAD test, recall CERAD test, AFT test and DSST test respectively. The total cognitive test score refers to the average of above four z-scores [14]. Higher cognitive test score indicates better cognitive function. Participants who reported “being limited in any way because of difficulty remembering or because experience periods of confusion” were defined as having subjective cognitive performance. Participants were defined as having subjective cognitive performance if the participant answered “yes” to the question: “being limited in any way because of difficulty remembering or because experience periods of confusion”.
Assessment of other covariables
We included variables of demographic characteristics and health behaviors that are possibly associated with cognitive function [15], including age (continuous variables), sex (male, female), race (non-Hispanic White, non-Hispanic Black, other Hispanic, other race), education level (college graduate or above, some college or associate degree, high school/GED or less ), the ratio of family income to poverty guideline (< 1.3, 1.3–3.5, > 3.5 ) [16] and alcohol consumption (drinker, non-drinker). Alcohol drinker was defined as those who had at least 12 alcohol drinks a year [17].
Statistical analysis
NHANES selected participants with a complex multistage probabilistic sampling design thus all analysis in this study were weighted with provided weight variables: WTDRD1, SDMVPSU and SDMVSTRA. Since we combined the 2011–2012 and 2013–2014 cycle, the weights of the combined study population were calculated as 1/2* WTDRD1 (https://wwwn.cdc.gov/nchs/nhanes/tutorials/module3.aspx).
Initially, we inspected the characteristic of the study population across four quartiles of LE8 score. After examined the normality of variables’ distribution and the homogeneity of variance, continuous variables were described with mean and standard deviation [mean (SD)] and compare with Wilcoxon rank-sum test while categorized variables were described as the case amount and its percentage [n (%)] and compared with chi-squared test. Afterwards univariable regression (linear regression for cognitive test score, logistic regression for subjective cognitive performance) was conducted to select covariables that were significantly associated with cognitive performance.
Cognitive performance models
We constructed three regression models to explore the association between LE8 score and cognitive performance, both as continuous variables and categorized variables. Model 1 wasn’t adjusted. Model 2 was adjusted for age, gender, and race. Model 3 was adjusted for age, gender, race, family income, education, and alcohol consumption. We also applied restricted cubic spline (RCS) models to explore the dose-response relationship in the above three models. The 5th, 35th, 65th, and 95th percentiles of the total LE8 score distribution were chosen as the knots of the RCS curves [18]. The R² (coefficient of determination) metrics were derived from our multivariable linear regression Model3 (Supplement Fig. 6). The P– non-linear value of RCS was obtained using a likelihood ratio test (LRT) to assess whether the higher-order coefficients of RCS curve are significantly different from zero. This test was conducted using the rms package in R.
Subjective cognitive performance models
We explored the effect of individual LE8 metrics on cognitive performance in a full-adjusted multivariable regression model. In order to validate the reliability of regression model, Receiver Operating Characteristic (ROC) curves of LE8 (both categorized and continuous) were plotted (Supplement Fig. 6). To assess the predictive capacity of LE8 for subjective cognitive performance, we compared the ROC curves of LE8 in relation to cognitive test scores and subjective cognitive performance. For the ROC analysis, cognitive test score was converted into a binary variable according to the lower quartile.
Subgroup models
To identify the subpopulation that benefits most from elevating LE8 score, the study population was stratified by all the variables in Model 3. We then calculated the regression coefficients of LE8 score in different subgroups. P values for interaction were calculated using likelihood ratio tests.
Cross-validation analysis
We made stratified ten-fold cross-validation with ten independent repetitions (10 × 10 CV) on both the objective cognitive testing and subjective cognitive assessment datasets. Model performance was quantified using R², providing robust measurement of predictive consistency and variance explicability (Supplement Table 6).
All statistical tests were two-tailed and conducted with R v. 4.2.1 statistical analysis software. Adobe Illustrator v2023 was used for figure preparation. P < 0.05 was considered statistically significant.
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