SBIR-STTR Award

This proposed SBIR study is for the advancement to market of a medical system that automatically and quickly measures and quantifies EEG signals to correlate with clinical staging and cognitive impairment associated with Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). The envisioned system – designed to be used in emergent, inpatient, ambulatory and research settings – will provide automatic, instant quantitative results to guide medical practitioners and researchers. It could be used as a diagnostic or monitoring tool or integrated into goal-directed therapies. Our envisioned system is based on an algorithm called Multifractal Detrended Fluctuation Analysis (MF-DFA) of EEG. The theoretical considerations about underlying cortical neuronal activity, the experimental results obtained in distinguishing states of consciousness, and the preliminary data obtained by this study’s scientific team strongly support investigating the potential of MF-DFA as a diagnosis and treatment tool for AD/MCI. A biomarker derived from EEG signals that correlates with AD/MCI’s executive function deficits and associated cortical network dysfunction would be an important clinical and research tool. Its advantages for both screening and follow-up diagnosis and monitoring compared to current neuroimaging and neuropsychological procedures would be low cost, convenience and quickness. Such an EEG-based biomarker for executive function deficits would be a major innovation for clinicians, given the diagnostic uncertainty, AD/MCI’s high prevalence and as- sociated morbidity. The envisioned system’s tests would (1) improve the accuracy of AD/MCI’s diagnosis and progression meas- urement; (2) be capable of being used in clinical and research settings across the spectrum of care; (3) give real- time, actionable clinical information; (4) enable diagnostic and monitoring procedures that are less expensive than currently available procedures; and (5) provide physicians and researchers a tool to measure the efficacy of pharma and other therapies. Preliminary research data show that the device may also assess brain dysfunc- tion caused by sleep disorders, other dementias, and traumatic brain injury. This proposed study is aligned with the limited purpose, scope and budget of SBIR Phase I studies. The specific purpose is to obtain reasonably quickly and inexpensively 'go/no-go' guidance to continue pursuing the devel- opment of our envisioned system. Specifically, the study’s aims are to further demonstrate what is shown by our preliminary data that MF-DFA is sensitive and specific for diagnosing the cognitive and functional impairment of AD/MCI. A 'go' study result would justify future studies including SBIR Phase II projects, some of which will rigorously investigate the method’s specificity, sensitivity, repeatability and reliability. This study will perform MF-DFA on the EEG tracings of 50 de-identified clinical cases, each with EEG traces and quantitative measures of depression and clinical staging, selected from a database owned by BBA Health, Inc. The database contains age-matched elderly individuals followed over a five-year period, many of whom devel- oped MCI or AD during the study. The patients underwent quarterly resting state EEG (3 min), and yearly infor- mation was collected about subjects’ age, demographics (ethnicity, gender, years of education), actual clinical diagnosis, Folstein Mini Mental Status Exam (MMSE) scores, Hamilton Depression Rating Scale scores (Ham- D), and Alzheimer's Disease Assessment Scale-cognitive subscale scores.

Public Health Relevance Statement:
PROJECT NARRATIVE This study is for the advancement to market of a medical device system that automatically and quickly measures and quantifies EEG signals to correlate with AD/MCI’s clinical staging and cognitive impairment. The envisioned system – designed to be used in emergent, inpatient, ambulatory and research settings – will provide automatic, instant quantitative results to guide medical practitioners and researchers. It could be used as a diagnostic or monitoring tool or integrated into goal-directed therapies.

Project Terms:
Activities of Daily Living; Age; Algorithms; Alzheimer disease detection; Alzheimer's Disease; base; Biological Markers; Brain; brain dysfunction; Budgets; Caring; Clinical; clinical application; clinical Diagnosis; Clinical Research; clinically actionable; Cognition; Cognitive; Cognitive Therapy; commercial application; Conscious; cost; Data; Databases; Dementia; demographics; design; Development; Device Designs; Devices; Diagnosis; diagnosis standard; Diagnostic; direct patient care; Disease; Education; Elderly; Electroencephalography; Ethnic Origin; European; Executive Dysfunction; executive function; FDA approved; follow-up; Fractals; functional disability; Future; Gender; Goals; Gold; Hamilton Rating Scale for Depression; Health; High Prevalence; Human; impaired capacity; Impaired cognition; improved; indexing; Individual; innovation; Inpatients; Legal patent; Ligands; man; Measurement; Measures; Medical; Medical Device; Memory; Mental Depression; mental state; Methods; mild cognitive impairment; Monitor; Morbidity - disease rate; network dysfunction; Neurocognitive Deficit; Neurodegenerative Disorders; neuroimaging; Neurons; neuropathology; neuropsychiatry; Neuropsychology; novel; off-patent; Patients; Performance; Phase; phase 1 study; Physicians; Physiology; Positron-Emission Tomography; Procedures; Quality of life; Research; Research Personnel; Rest; screening; Severities; Signal Transduction; Sleep Disorders; Small Business Innovation Research Grant; Specificity; Staging; System; Testing; Time; tool; Tracer; Translating; Traumati