Altoida's Digital Neuro Signature and the future of population-level brain health management

The approval of Aducanumab was the beginning of an inflection point in global brain health and dementia management. Altoida has developed a platform that could set the new gold standard in cognitive function measurement at the population level, and help pioneer predictive dementia diagnosis.

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Dementia as a Population Health Issue

The World Health Organization estimates that approximately 50 million people worldwide have dementia. With nearly 10 million new cases each year1, it’s projected that the global dementia case total will eclipse 80 million by 2030 and 150 million by 2050.

A key accelerant to the increasing global burden of dementia is the rising number of dementia cases in low- and middle-income countries. These countries are more likely to lack sufficient public health resources to control the risk factors of the disease and assess, diagnose, and treat the disease in a timely and cost-effective manner. 


Solutions in Dementia Detection and Treatment

Assessing dementia: traditional neuropsychological tests and brain scans

Limitations in traditional neuropsychological tests, such as the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Exam (MMSE), as the “gold standard” for testing have hindered our ability to effectively assess and treat dementia at the population level. 

One such limitation is how significantly an individual’s performance can be affected by their “good days” and “bad days.” This day-to-day variability can lead to an inaccurate understanding of one’s true cognitive function, both in cross-sectional and longitudinal assessment. Traditional neuropsychological tests are also not as highly ecologically valid as future state testing could be. Because many of these tests solely assess speed- and accuracy-based metrics, they don’t necessarily test the brain under a cognitive load representative of complex daily tasks, nor can they capture the wealth of data that digital tools can. Therefore, they may not be ideal tools to collect data that is generalizable to real-world brain function. Furthermore, traditional neuropsychological tests are time-consuming and complex to administer. These limitations contribute to lower testing rates and poor data on cognitive function, which are two rate-limiting factors in diagnosing and treating dementia.

Fig 1. Day-to-day variability in testing can overshadow true performance due to external factors (environment) and internal factors (anxiety, motivation, etc.). Reprint courtesy of Martin Sliwinsk, permission granted2.

Beyond neuropsychological tests, brain scans (CT, MRI, or PET) are a hallmark in today’s standard of care for dementia diagnosis. However, these procedures are expensive, invasive, and limited in their ability to predict disease onset. 

At large, there is a clear opportunity and the right level of technological maturity for innovation to drive more scalable assessment and management of cognitive health at the population level.

Treating dementia: pharmacological and behavioral therapies

Preventative care is a promising opportunity to combat dementia onset and progression. The Lancet Commission estimates 40% of all dementia cases could be prevented or delayed by targeting 12 risk factors throughout life3

With the United States Food and Drug Administration’s (FDA’s) recent approval of Aduhelm (aducanumab), there is revived hope for a therapy that can address a defining pathology of Alzheimer’s disease dementia by reducing amyloid-beta plaques in the brain. However, the drug’s exciting and broad approval has been met with questions around the clinical trial evidence and critique that the drug may not meaningfully improve cognitive function or slow the rate of cognitive decline.

How Altoida can address today’s challenges with an innovative and scalable solution

Altoida is creating an emerging gold standard in cognitive assessment. Rather than assess cognitive function with a traditional memory test, Altoida’s platform uses ecologically valid digital and augmented reality (AR) activities to immerse the user and assess the brain under a cognitive load representative of complex tasks of daily living. From these activities, Altoida collects data from the electronics sensors in the users’ device to analyze 748 proprietary digital biomarkers and provide both an objective measurement of brain function across 11 neurocognitive domains and subdomains (backed by DSM-5 criteria4) and a novel Digital Neuro Signature score.

Altoida’s platform and Digital Neuro Signature (DNS) score provide a more efficient, accurate, and sensitive assessment of cognitive function than traditional neuropsychological tests, both in cross-sectional and longitudinal evaluations.

Compared to traditional neuropsychological tests, Altoida’s platform and DNS score result in remarkably faster evaluations and reporting (10-12 min vs 45–120 min). As shown in our recently published NPJ Digital Medicine manuscript5, Altoida’s DNS score outperformed traditional neuropsychological test metrics in accurately and reliably capturing intraindividual cognitive function in two semi-naturalistic observational experiments in laboratory and clinical settings (n=525). Results show that the DNS score, relative to traditional neuropsychological test metrics, was consistently more sensitive at capturing longitudinal individual-level changes across multiple neurocognitive domains for three groups of participants (healthy controls, patients with mild cognitive impairment, and patients with Alzheimer’s disease). 

In addition to measuring and monitoring cognitive function, data demonstrated that the DNS score could be used as a predictor of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). In the study, the DNS score was used to predict conversion events 6–8 months prior to annual follow-ups for a mixed pool of MCI amnestic individuals. Conversion events were predicted consistently and successfully for 36 months of follow-ups to enable a timely diagnosis of AD, whereas the traditional neuropsychological tests did not detect intra-individual change and subsequent conversion nearly as quickly.


Opportunity and Use Cases 

Altoida’s platform and DNS score provide both a precise and pragmatic solution to population-level dementia management. With Altoida’s platform and DNS score, it is possible to enable higher rates of brain health assessment and to develop risk phenotypes. As such, the DNS score could be an instrumental metric to determine who should receive therapies in a population (including pharmacotherapy), when they should receive them, and at what dose.

This approach aligns with the Precision and Personalized Population Health (P3H) framework6,7 put forth by Dr. Azizi Seixas and their team. P3H attempts to understand, manage, and treat health and wellness along the continuum from discovery (the process of finding common and unique causes of disease) to treatment optimization and adherence (the process of finding the right treatment, for the right person, at the right time, with the optimal dosage). The P3H continuum can be summarized using the “D6AEs'' framework: Discovery, Awareness, Avoidance, Access, Assessment, Acceptance, Adherence, and Efficacy/Effectiveness of solutions. Alotida’s platform and DNS score are well-positioned to offer value across all 8 domains of the P3H continuum. 

Discovery 

Altoida’s platform and DNS score can sharpen our understanding of the etiology of dementia. They are built on a test activity battery that enables highly personalized cognitive function assessment using novel data inputs, including functional performance, visuospatial performance, voice, gait, and eye-tracking, among others. Relative to traditional neuropsychological tests, the field of data collected with Altoida’s platform is drastically expanded, which has the potential to also expand, democratize, and revolutionize the field of data available to clinicians and researchers seeking to understand personalized causes and trajectories of dementia. Furthermore, the DNS score takes in these expanded data inputs to detect unique biological signatures (mapped over multiple neurocognitive domains), and highlight changes from normal cognitive function to MCI, and from MCI to dementia-related disease. From an etiological perspective, the DNS score provides clinicians and researchers a natural experimental framework to establish causal links between changes in cognitive function and endogenous and exogenous factors. 

Awareness and Avoidance (prevention)

Altoida’s DNS score provides a unique opportunity to increase awareness of the risk of developing MCI and dementia and to engage populations in preventive and corrective strategies to both arrest cognitive decline and improve cognitive function. Metrics reported within Altoida's platform, like the DNS score and granular neurocognitive domain scores, are needed to improve the selection of candidates who can benefit the most from preventative therapies, intervention strategies, and existing or novel drugs.

Access and Assessment

Altoida’s platform opens the door for economical, user-friendly, and highly accurate cognitive assessment at scale. In addition to high ecological validity, the 10-minute test activity battery feels like a set of smartphone games rather than a cumbersome memory test and is designed to be completed in any environment. With this approach, cognitive assessment can be conducted at scale in diverse settings such as health clinics, research laboratories, large health systems, and rural settings. Patients using Altoida's platform can also easily be monitored remotely ㇐ a trend that is poised to see continued expansion in the wake of COVID-19. 

Acceptance and Adherence 

Altoida’s platform and DNS score address several of the acceptance and adherence challenges that are characteristic of traditional neuropsychological tests. Internal factors that can heavily affect performance on traditional cognitive tests, such as motivation, concentration, attention, and available time, are generally limited in their impact on performance when using Altoida’s platform. By providing highly ecologically valid test activities and an immersive and engaging user experience, Altoida’s platform mitigates the effects of day-to-day variability in these and other factors on performance and provides a truer understanding of cognitive function.

Efficacy/Effectiveness of dementia treatments

Altoida’s DNS score is constructed to be an ideal companion tool for pharmacological, behavioral, and cognitive therapies. Because of the hyper-sensitivity of the DNS score to intra-individual change, it can be used to assess the effectiveness of therapy at improving or slowing the decline of cognitive function over time. Altoida’s DNS score can be used as a sensitive monitoring biomarker that detects granular changes in real-world function. These changes could be extremely meaningful in understanding clinical improvement or progression but ultimately would have been missed by traditional neuropsychological tests.


Contributors:

This post was created by Azizi Seixas, Ph.D., Ioannis Tarnanas, Ph.D., Irene Meier, Ph.D., Arzu Çöltekin, Ph.D., Max Bügler, Ph.D., Robbert Harms, Ph.D., and Henry Peck.


References:

1. “Dementia.” WHO, 21 Sept. 2020, www.who.int/news-room/fact-sheets/detail/dementia.

2. ALZFORUM. Cognitive testing is getting faster and better. https://www.alzforum. org/news/conference-coverage/cognitive-testing-getting-faster-and-better (2017).

3. “Differences in the Potential for Dementia Prevention Between Major Ethnic Groups Within One Country: A Cross Sectional Analysis of Population Attributable Fraction of Potentially Modifiable Risk Factors in New Zealand.” The Lancet Regional Health, Western Pacific, 5 Aug. 2021, secure.jbs.elsevierhealth.com/action/cookieAbsent.

4. Sachdev, Perminder, et al. “Classifying Neurocognitive Disorders: The DSM-5 Approach.” ResearchGate, 3 Dec. 2020, www.researchgate.net/figure/Neurocognitive-domains-The-DSM-5-defines-six-key-domains-of-cognitive-function-and-each_fig1_266325299.

5. Meier IB, Buegler M,  Harms R,  Seixas AA, Çöltekin A, Tarnanas I. Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer’s disease: the Altoida large cohort study. npj Digital Medicine (2021)4:101 ; https://doi.org/10.1038/s41746-021-00470-z.

6. Seixas AA, Moore J, Chung A, Robbins R, Grandner M, Rogers A, Williams NJ, Jean-Louis G. Benefits of Community-Based Approaches in Assessing and Addressing Sleep Health and Sleep-Related Cardiovascular Disease Risk: a Precision and Personalized Population Health Approach. Curr Hypertens Rep. 2020 Jul 15;22(8):52. doi: 10.1007/s11906-020-01051-3. PMID: 32671477.

7. Seixas A, Conners C, Chung A, Donley T, Jean-Louis G. A Pantheoretical Framework to Optimize Adherence to Healthy Lifestyle Behaviors and Medication Adherence: The Use of Personalized Approaches to Overcome Barriers and Optimize Facilitators to Achieve Adherence. JMIR Mhealth Uhealth 2020;8(6):e16429 doi: 10.2196/16429 PMID: 32579121 PMCID: 7381082.

Ioannis Tarnanas

Chief Scientific Officer, Altoida Inc