Digital Endpoints: Brain

Real-World Assessment of Neurological Outcomes

Real-World Assessment of Neurological Outcomes

Neurodegenerative disease refers to a heterogenous group of conditions in which the nerve cells of the central or peripheral nervous system do not function appropriately. Given the brain is the central component to normal body functioning, neurological impairments present a wide variety of symptoms. For example, Parkinson’s and Alzheimer’s Diseases primarily manifest as motor and cognitive impairments, while patients with Rare Disease such as Rett Syndrome and Spinal Muscular Atrophy can experience debilitating respiratory dysfunction.

Selecting the most appropriate outcome measure not only depends on the disease pathophysiology and clinical manifestation, but also on the aspects of health that are most meaningful to the patient and caregiver. VivoSense software allows for multiple timeseries data streams to be synchronized and integrated with subjective ePRO/eCOA data for complex analysis and visualization. This degree of contextualization of real-world data allows for a more holistic approach to understanding how neurodegeneration simultaneously impacts multiple body systems, and the patient’s lived experience.

Wearable Technology

Because neurodegenerative disease can impact nearly all physiologic systems, there are many relevant wearable and remote monitoring technologies. Importantly, they provide an opportunity for clinicians and researchers to simultaneously monitor several neurological related outcome measures that directly reflect how a patient feels and functions in their own real-world environment.

These data can be further contextualized by overlaying episodic patient self-report or other clinical test results.

Kinematic Sensors - Including accelerometers, gyroscopes and magnetometers can be used to assess motor function and physical activity/inactivity. Specifically, they can be used to identify and quantify the time a patient spends participating in real-world behaviors, gait parameters (stride length and velocity), and change in direction or turning behavior - an outcome relevant for neurodegenerative diseases, such as Parkinson’s disease.

Thoraco-Abdominal Respiration - Dual-band respiratory inductance plethysmography (RP) sensors are the gold standard for continuous, unobtrusive respiratory monitoring. They are widely used in clinical and research settings, and particularly in polysomnography (sleep studies). Thoracic and abdominal bands allow measurements of both breathing compartments, providing accurate volume and phase relation measurements in addition to simple respiration metrics of rate and timing.

ECG and PPG - Neurologic related cardiac and vascular events such as arrhythmias and decompensation can be monitored with wearable ECG and PPG technology. ECG electrodes can be implemented in shirt, patch, and strap form factors and range from single to 12-lead. Sites for PPG measurement include the wrist (e.g., watch) or more traditionally, the finger or ear.

ECG Derived Respiration (EDR) – EDR allows for continuous measurement of respiration rates and timing and has been analytically validated during sleep. Long-term monitoring of transient respiratory events is possible while simultaneously enabling ECG measures to be used in a clinical endpoint. E.g., EDR and HR.

Outcome Measures

B6ME (Best 6-Minute Effort)

Sensor Modalities: Accelerometer, Gyroscope

Clinical Use Examples: Monitoring biomarker for assessing fluctuations in functional capacity during “on-off” cycles in patients with Parkinson’s disease

Stride/Length Velocity

Sensor Modalities: Accelerometry, Gyroscope

Clinical Use Examples: Response biomarker for quantifying change in walking capacity in patients with motor impairment

Sit-to-Stand Rise Time

Sensor Modalities: Thigh worn accelerometer

Clinical Use Examples: Response biomarker for quantifying change in functional capacity in highly sedentary populations such as patients with advanced Parkinson’s Disease, Alzheimer’s Disease and Rare Disease

Time to First Step

Sensor Modalities: Thigh worn accelerometer

Clinical Use Examples: Monitoring or Response biomarker for quantifying change in functional capacity in clinical populations with balance and stability impairment

Sleep Parameters

(Duration, Efficiency, Timing)

Sensor Modalities: Accelerometry, EEG

Clinical Use: Monitoring biomarker for dementia patients experiencing sundowning and shifts in circadian rhythm

Heart Rate Variability (HRV)

Sensor Modalities: ECG

Clinical Use: Prognostic biomarker for patients experiencing cardiac autonomic neuropathy

Respiratory Function

(Resting Respiratory Rate, Phase Relation, Timing)

Sensor Modalities: RP, ECG, PPG

Clinical Use Examples: 
Response biomarker to quantify the change in ratio of rib vs. abdomen contribution to breathing in patients with Rett syndrome

Monitoring biomarker to assess the progression of respiratory insufficiency in patients with ALS

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