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Five minute dementia screening iPad app debuts

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An iPad app developed in the United States could help doctors screen for a wide range of neurological diseases, such as Parkinson’s and dementia, in five minutes or less.

Developed at Northwestern Medicine in Chicago, the NIH (National Institutes of Health) Toolbox V3 iPad app allows time-strapped clinicians to quickly but thoroughly assess patients, from young children who need screening ahead of school to older people who may be concerned about dementia.

The developers claim that tests that would once have taken two or three hours to complete can now be reliably done in under 30 minutes.

Project leader Richard Gershon, vice chair for research in the department of medical social sciences at Northwestern University’s Feinberg School of Medicine, said: “The problem in clinical care today is nobody has time for long tests for everything; we need very brief tests.”

While some clinical screening tools require expensive custom hardware, this app = which can be downloaded from the Apple App Store – allows anyone with an iPad to access the full assessment suite of more than 50 tests spanning four areas – cognition, motor, sensation (hearing, smell, pain, vision and taste) and emotion.

COVID-19 patients complaining of “brain fog,” for instance, can now take several brief tests to determine what areas could be the target for cognitive rehabilitation.

Or someone who has recently lost their sense of smell can take the Toolbox’s olfactory test – and any others as need via the – to better understand if it could be an early sign of Parkinson’s disease.

Parts of the Toolbox are already being used at Northwestern to help detect dementia. And researchers are working on developing a self-administered version of the tests that could be taken in the waiting room before a patient’s visit with the results being sent straight into their electronic health record.

One example of a test to measure episodic memory is a series of pictures displayed on the screen describing a trip to the park. After they’ve been scrambled, the patient has to put the pictures back in order.

The NIH Toolbox has been in development for more than a decade. It was first launched in 2012 with a more portable iPad app unveiled three years later.

This newest version was originally intended solely for researchers. But it was decided to release it for clinical use following appeals from physician-scientists and psychologists looking for a way to improve patient care by allowing access to a wide variety of easily administered tests.

As an example, the researchers say it could be used for an older adult presenting to their neurologist with complaints of cognitive decline.

The examiner could assess the patient’s cognitive abilities as well as emotional functioning, such as depression and anxiety, which can also contribute to those complaints.

The NIH Toolbox has been developed by more than 250 scientists and sponsored by 15 institutes of the Maryland-based National Institutes for Health, that make up the NIH Neuroscience Blueprint, a collaborative framework supporting research on the nervous system.

Because the app is being distributed through the Apple App store, Richard Gershon and his colleagues don’t always know everyone who is using the Toolbox, but by tracking analytics detailing how often and where it’s purchased, they know it is currently in 21 countries.

The earlier V2 version of the app has been used by 3,000 researchers from 1,200 institutions globally and has been authenticated in 300 separate validation studies.

Dr Igor Koralnik, chief of neuro-infectious disease and global neurology at Feinberg, said: “The NIH Toolbox cognitive tests are extremely useful for testing the cognitive function of our neuro covid-19 clinic patients complaining of ‘brain fog,’ The results are adjusted according to age, education and other demographics, allowing us to tell our patients immediately of their performance, and if they may benefit from cognitive rehabilitation.”

Additionally, a Northwestern-led National Institute on Aging cohort study examining midlife determinants of later-life cognitive decline and dementia, is using the Toolbox to capture a range of conscious mental abilities.

Michael Wolf, associate vice chair for research in the department of medicine at Feinberg, commented: “Patients find the tests easy to use and are more engaged than with other standard measures we have deployed previously. Overall, this is an incredibly important research assessment tool that will help our work be more translatable to other studies.”

The app has been made available in both English and Spanish. Hebrew and Arabic versions are set to be released in late 2023. Additionally, numerous studies in Africa are using the Toolbox and have incorporated a translation app to communicate in Swahili, Dholuo and Twi.

Many of the streamlined tests are accomplished through computer adaptive testing. This means the app is constantly adjusting the questions to meet the level of the person being tested, eliminating irrelevant questions.

Richard Gershon said: “We zero in on that person’s individual level of functioning and don’t waste their time asking questions far above or below their ability.”

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AI tool flags undiagnosed Alzheimer’s cases

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A new AI tool flags early Alzheimer’s, identifying about four in five people who would otherwise be missed by clinicians.

Trained on UCLA Health patient records and tuned to work more fairly across Black, Latino and Asian patients who are often underdiagnosed, the system aims to find people earlier, when treatment and lifestyle changes can still help.

In tests on more than 97,000 UCLA Health records, the model reached a sensitivity of about 77 to 81 per cent across non-Hispanic white, non-Hispanic African American, Hispanic/Latino and East Asian groups, roughly double that of conventional supervised models, the authors report.

UCLA Health researchers developed the tool and built fairness measures into training before checking the model’s picks against genetic benchmarks.

Patients flagged as likely cases but previously unlabelled showed higher polygenic risk scores and APOE ε4 counts than those the system did not flag.

Polygenic risk scores measure the combined effect of multiple genes on disease risk, while APOE ε4 is a genetic variant linked to increased Alzheimer’s risk.

The AI looks beyond memory-related billing or diagnostic codes and finds patterns that include signals such as decubitus ulcers, commonly known as pressure sores, and palpitations, which could prompt clinicians to take a closer look and consider screening.

“We were able to capture about 80 per cent of the people who actually would have undiagnosed Alzheimer’s disease,” said Dr Timothy Chang.

He said studies estimate up to 40 per cent of Alzheimer’s cases go undiagnosed, a gap that hits Black and Latino communities especially hard.

The framework learns from both labelled Alzheimer’s cases and unlabelled patient records, using race-specific probabilistic labelling and post-processing cutoffs tuned for group benefit equality to reduce bias.

Rather than relying only on diagnostic codes, the model draws on a wide range of electronic health record features, including diagnoses, encounter history and age, helping uncover likely cases that never received a formal label.

Earlier detection matters because disease-modifying treatments and targeted clinical referrals are now an option for people in the earliest symptomatic stages of Alzheimer’s.

Amyloid-targeting therapies such as lecanemab and donanemab are intended for early disease, which makes timely screening and specialist evaluation more consequential for patients and families.

Lifestyle changes and symptom management remain key tools for slowing decline, planning care and helping families prepare.

Researchers stress that the tool is a flagging system, not a diagnosis, and that its output should trigger follow-up evaluation rather than replace clinical judgement.

The team plans prospective validation in partner health systems to test how well the tool generalises and how useful it is in real-world practice before any routine roll-out.

Models can reveal new biases when used outside the environment where they were trained. Clinicians and ethicists will also have to weigh benefits against the risk of false positives, added patient anxiety and uneven access to specialist care.

The coming months will focus on broader testing and conversations with health systems about how to roll out the technology responsibly, if future studies support its use.

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Gap partners with Spear Bio on Bio-Hermes-002

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Gap is partnering with Spear Bio on Bio-Hermes-002, an Alzheimer’s study comparing blood and digital biomarkers across cognitive conditions.

The observational platform study compares blood-based and digital biomarkers (measurable signs in blood or behaviour) across a broad range of cognitive conditions, alongside MRI and PET brain scans and diverse racial and ethnic groups, to generate data that may help predict, detect and diagnose Alzheimer’s disease and related dementias.

The study gathers data on how each biomarker, or combinations of biomarkers, perform in assessing, diagnosing or predicting pathologies linked to Alzheimer’s and related dementias, including amyloid and tau in the brain.

Amyloid plaques and tau tangles are abnormal protein deposits and are hallmark features of Alzheimer’s disease.

John Dwyer, president of GAP, said: “We’re proud to have Spear Bio as a valued partner in the Bio-Hermes-002 study.

“Their technology platform is consistent with our goal to catalyse and scale early-stage disease diagnostics and monitoring, therby transforming how we treat patients and conduct clinical trials for Alzheimer’s and related dementias.

“By advancing biomarker detection, we hope to accelerate meaningful progress for individuals and families affected by these conditions.”

In Bio-Hermes-002, Spear Bio will provide results of blood-based biomarker analysis using its SPEAR UltraDetect assay platform, which the company says offers attomolar sensitivity from a one microlitre diluted sample, and what it describes as superior specificity in a homogenous wash-free format, aiming to change early-stage diagnostics and monitoring.

This builds on findings from Bio-Hermes-001.

Data from Bio-Hermes-002 will be stored on the AD Workbench from the Gates Ventures Alzheimer’s Disease Data Initiative (ADDI).

The AD Workbench is a global, secure, cloud-based data sharing and analytics environment that enables researchers worldwide to share, access and analyse data across multiple platforms.

Spear Bio joins industry partners in the study, including Biogen, Eli Lilly and Company, IXICO and Roche, along with a growing list of partners providing blood-based biomarker assessments or digital assessments for Bio-Hermes-002.

To date, the partners include AINOSTICS, Alamar Biosciences, Beckman Coulter Diagnostics, Cambridge Cognition Limited, Cognivue, Cumulus Neuroscience Limited, Fujirebio, iLoF, LifeArc, Linus Health, Lucent Diagnostics, a Quanterix brand, Sunbird Bio and ViewMind.

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Insilico in US$66m deal for Parkinson’s drug

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Insilico Medicine has agreed a US$66m deal with a Chinese biotech for half of the rights to a brain-penetrant Parkinson’s drug.

Under the agreement, the artificial intelligence-powered drug developer will take the lead on bringing the preclinical asset, dubbed ISM8969, into a phase 1 trial.

Hygtia Therapeutics will then take over for further studies and onward toward regulators and commercialisation.

Ren Feng is co-chief executive and chief scientific officer at Insilico.

Feng said: “Targeting neuroinflammation via NLRP3 represents a scientifically sound and high-potential approach to treating neurodegenerative and age-related diseases.

“However, developing a safe molecule with good blood-brain barrier penetration remains a formidable obstacle for drug developers.

“Through our generative AI platform, we have designed a molecule specifically engineered to overcome this barrier.

“We are pleased to partner with Hygtia Therapeutics.

“We believe that through our combined efforts, we can accelerate its clinical progress to address significant unmet medical needs.”

ISM8969 is an NLRP3 inhibitor.

NLRP3 is a protein involved in inflammation, and blocking it is being explored as a way to address a range of neuroinflammatory and cardiometabolic diseases. Interest in NLRP3 inhibition has increased in the past year.

Earlier this month, Eli Lilly paid US$1.2bn to acquire Ventyx Biosciences in the wake of a phase 2 study tying Ventyx’s lead NLRP3 inhibitor to improvements in Parkinson’s symptoms.

That same NLRP3 inhibitor had also been shown to cut levels of a biomarker for stroke and other serious risks by almost 80 per cent within a week in a separate mid-stage study.

Preclinical data for ISM8969 have “demonstrated the molecule’s robust efficacy, favourable safety profile and marked anti-inflammatory activity in various disease models,” said Insilico, which also noted the therapy’s “desirable blood-brain barrier penetration.”

The blood-brain barrier is the protective barrier around the brain that many drugs struggle to cross.

Insilico, which went public on the Hong Kong Stock Exchange last month, said it had discovered ISM8969 via its generative chemistry engine Chemistry42.

As well as an upfront fee of US$10m, Insilico is in line for up to US$56m in milestone payments from Hygtia.

Insilico has attracted interest from pharmaceutical companies for its AI-enabled drug discovery technology, including Sanofi, Pfizer, Menarini Group and Boehringer Ingelheim.

Most recently, Lilly agreed a deal worth more than US$100m in November.

Hygtia, which was founded last August after being incubated by Fosun Pharma, said the agreement with Insilico “marks a pivotal step in our global strategy.

This partnership aligns with our strategy to expand our innovative neuroscience pipeline through high-quality assets.”

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