Non-invasive assessment of glymphatic flow and neurodegeneration from a wearable device
Inventors
Dagum, Paul • Kovacs, Gregory T. A. • Giovangrandi, Laurent B. • Weber, Carl J. • Student, Joerg C. • Whipple, Nathan • Kaplan, Jonathan I.
Assignees
Triple Ring Technologies Inc • Applied Cognition Inc
Publication Number
US-11478184-B1
Publication Date
2022-10-25
Expiration Date
2042-04-05
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Abstract
A computer-implemented method and system includes accessing neurophysiological and neurovascular data recorded during sleep. A function mapping is executed from said neurophysiological and neurovascular data to a target that is one of a glymphatic flow marker, a molecular analysis marker of neurodegeneration, or a neuroimaging marker of neurodegeneration. A target prediction model is output based on the function mapping. The target prediction model can receive new neurophysiological and neurovascular data and output a predicted marker of neurodegeneration.
Core Innovation
The invention is directed to systems and methods for non-invasive assessment of glymphatic flow and neurodegeneration by utilizing a wearable device capable of collecting neurophysiological and neurovascular data during sleep. These data are then processed via function mapping using one or more computer processors to produce a target prediction model that can estimate biomarkers such as markers of glymphatic flow, molecular analysis markers of neurodegeneration, or neuroimaging markers of neurodegeneration. The wearable device includes sensors for recording electroencephalogram (EEG) and neurovascular signals and is designed to transmit the collected data wirelessly to a secondary computing device for further analysis.
The primary problem addressed is the current reliance on invasive, expensive, and complex procedures, such as PET scans and lumbar punctures, to measure functional integrity and pathological protein accumulation in the brain associated with neurodegenerative diseases. Such invasive techniques require hospital or clinic environments, add patient burden, and are not suited for broad screening or ongoing monitoring. The invention therefore proposes a wearable system that can non-invasively monitor markers indicative of glymphatic function and brain proteinopathy using sensor-derived sleep data.
Training data collected from wearable sensors are functionally mapped, using machine learning models such as random forests, to ground-truth target biomarkers derived from molecular analyses or neuroimaging. Once trained, the target prediction model can be applied to new, unseen physiological and vascular data collected during sleep to screen for or monitor disease progression, reduce reliance on invasive clinical procedures, and support therapeutic intervention assessment. The system is configurable to capture various sleep-related neurophysiological and neurovascular features, utilize ergonomic sensor assemblies, and deliver actionable non-invasive monitoring relevant to neurodegenerative disease management.
Claims Coverage
The claims section describes multiple inventive features, particularly focusing on the wearable system, method for mapping sleep-derived neurophysiological and neurovascular data to neurodegeneration markers, and related system components.
Non-invasive wearable device with left and right ear canal electrodes for simultaneous EEG and transcranial impedance measurements
The system includes a wearable device comprising left and right ear canal electrodes multiplexed to make both electroencephalogram (EEG) and transcranial impedance measurements during sleep. The device records neurophysiological data (EEG measurements from both left and right ear canal electrodes) and neurovascular data (transcranial impedance measurements from both left and right ear canal electrodes).
Transmission of collected sleep neurophysiological and neurovascular data to a remote computing device
A transmission module of the wearable device is configured to transmit the neurophysiological and neurovascular data, collected during sleep, to a computing device for further processing.
Machine-executed function mapping from sleep-derived sensor data to glymphatic flow marker
The method involves executing, on one or more computer processors, a function mapping that processes the accessed neurophysiological and neurovascular sleep data to yield a target that is a marker of glymphatic flow. A target prediction model based on this function mapping is output.
Target prediction model for non-invasive biomarker estimation
A target prediction model is generated and is capable of receiving as input new neurophysiological and neurovascular data and outputting a predicted marker of glymphatic flow. Additional mappings can be performed from the marker of glymphatic flow to further targets such as molecular analysis markers or neuroimaging markers of neurodegeneration.
Wearable device with pressurized ear canal bladders to enhance electrode contact
The wearable device comprises left and right ear bladders that are pressurized inside the ear canals to increase the interfacial contact of the electrodes with the ear canal wall, thereby improving measurement quality.
Incorporation of additional sensors for comprehensive neurovascular assessment
The wearable device is further specified to include photoplethysmograph and inertial measurement unit sensors, enabling collection of additional neurovascular data such as heart rate variability, resting heart rate, pulse transit time, pulse wave velocity, and respiratory rate during sleep.
The inventive features collectively cover a non-invasive wearable device and associated software and methods for comprehensive acquisition and processing of sleep neurophysiological and neurovascular data, enabling prediction of glymphatic flow and neurodegeneration markers without requiring invasive clinical methods.
Stated Advantages
Enables non-invasive screening and monitoring of neurodegenerative proteinopathy using wearable sensors, reducing reliance on invasive and costly clinical procedures.
Allows repeated, at-home measurements for monitoring disease progression or therapeutic response, enhancing the practicality and accessibility of neurodegenerative condition management.
Facilitates early intervention by enabling detection of glymphatic flow dysfunction and neurodegeneration markers during the subclinical or pre-clinical disease period.
Improves patient compliance and reduces burden by eliminating the need for hospital visits, external wiring, or trained technician operation for data collection.
Documented Applications
Screening for neurodegenerative diseases such as Alzheimer's disease by predicting markers indicative of glymphatic flow or proteinopathy.
Non-invasive monitoring of disease progression in patients with neurodegenerative disorders using repeated sleep-derived sensor data.
Determining and evaluating the effect of therapeutic interventions—such as cardiovascular, pharmaceutical, neuromodulation, diet, or sleep interventions—on glymphatic flow and neurodegeneration markers.
Enabling longitudinal assessment and monitoring of neurodegeneration biomarkers without requiring repeated invasive testing.
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