The Connected Self: The Era of Digital Biomarkers in Neurology

Women’s Brain Project & Altoida announce results highlighting sex-based differences.

The future of medicine will be driven by connected, portable — even ingestible — devices capable of acquiring information with AI-driven, real-time analysis.

Increasing digitalisation and the emergence of more precise sensors have ushered in the era of digital biomarkers. The word “biomarker” normally indicates any type of measurement or indicator that marks a biological state of the system, e.g. as blood values or vital signs. Unlike traditional biomarkers, digital biomarkers are objective, quantifiable physiological and behavioural data collected and measured by portables, wearables, implantables, or digestibles.

The increasing integration of digital tools in healthcare will improve disease prevention, diagnosis, and treatment. Core drivers include the emergence and consolidation of care needs at individual and population levels, and the advance of machine learning and AI.

One of the key elements to boost understanding of the impact the technology will have is the distribution of information and communication technologies, or devices capable of acquiring, processing, and transmitting information. The smartphone is key. There are 6.6 billion smartphone users, growing at an annual rate of 4.9 percent — 2.9 billion more than in 2016, says the market research report Statista 2022.

According to trends, by 2027 that figure will hit eight billion.

Internet use has also grown in recent years. In April 2022, 63 percent of the global population — roughly five billion users — was connected. Of that number, 4.65 billion are on social media. The internet penetration rate is the highest value in Northern Europe, some 98 percent of the population.

Wearable devices are equipped with sensors that can capture healthcare information in real-time. These portable devices have a higher processing power Moore’s Law predicted exponential growth in the computing capacity of microprocessors. This has enabled smaller, more affordable devices.

Deciphering the genetic code is one of the greatest medical achievements. The entire project cost for the Human Genome Project was around $2.7bn. The human genome contains six billion letters. The first cost about a billion dollars to sequence. Now it’s less than $1000, so a one-million-fold reduction.

The digital revolution draws similar parallels. There has been growing capacity in systems biology and medicine to decipher the biological complexity and evolution of diseases. Coupled with access to information and growing interest in patient empowerment via consumer-driven healthcare and social networks, this is heading towards the “4Ps” in medicine;: Preventive, Predictive, Personalised, and Participatory.

Digital biomarkers can enable high frequency, longitudinal and objective measurements. They can monitor patients in real-time to assess response to therapy and disease progression — without the need for clinical evaluation. They often show greater prediction and identification sensitivity than traditional methods.

There has already been an impact on neurodegenerative diseases, for example the digital medical application of instrumental activities of daily living (iADL), a predictive biomarker of conversion from mild cognitive impairment due to Alzheimer’s disease to dementia in individuals aged over 55.

Despite the great promise, multiple factors — demographic, genetic, and phenotypic — can influence the status of biomarkers and their predictive value.

Gender and sex have a prominent role in the development of many medical conditions. But sex interactions are not always properly addressed in clinical research, which could negatively impact the generalisation of results.

Sex is a crucial source of Alzheimer’s heterogeneity and a promising target for personalised care. Considering gender in predictive diagnostics, targeted prevention, and gender-specific considerations in clinical trials allows for better diagnostic and prognostic stratification accuracy. It can also accelerate targeted drug development.
Swiss-based research group the Women’s Brain Project reported a research study that explores using data from digital biomarkers to identify differences in neuro-cognitive performance based on gender.

Promising biomarker-based digital technology for early diagnosis of Alzheimer’s was used to achieve this goal, using a digital cognitive assessment provided by Altoida, which is known as the neuro-motor index (NMI), which leverages a range of smartphone- or tablet-based activities using augmented reality and finger motor activities to simulate live daily instrumental activities.

Data analysis revealed that healthy males and females have detectable and unexpected differences in neurocognitive performance when evaluated with Altoida. The result is surprising, as it suggests that ignoring the complex interaction between gender and predictive digital biomarkers could compromise the early detection of disease.

The Women’s Brain Project group suggests that the influence of sex on disease fades with the severity of the illness. It could be hypothesised that men and women differ in several characteristics at baseline, while these are progressively equalised with the progression of clinical symptoms over seven to 10 years.

These findings can impact:

Research into the pathophysiological mechanisms of Alzheimer’s, based on sex differences, with opportunities for personalised treatment.

Predictive Medicine: gender differences could enable more accurate predictions, critical to planning therapy and treatment options.

Precision Medicine could guide clinical practice by improving choices for prevention, diagnosis, and treatment options.

The future of research and patient care in general — and in dementia and neurodegenerative diseases in particular — is likely to be dominated by new digital tools.

The new applications add insight in specific fields of personalised care such as gender medicine, shedding light on the interplay between sex and the prevention and prediction of complex pathologies. The advances increase the understanding and treatment of diseases, and can address sex-related disparities in healthcare for a medicine that is more effective, and more just.