ACTIVAS DIAGNOSTICS, LLC — Department of Health and Human Services SBIR Phase II: NIA

Description

Abstract There is an urgent need for new diagnostic approaches for early identification and progression in Alzheimer s diseaseADand related dementiasADRDNIA s Strategic Direction C and D to improve our understanding and develop interventions for mild cognitive impairmentMCIthe prodrome of ADThis proposal focuses on sleep statusa known hallmark of neurological diseaseand commonly present in MCI ADSleep disorder is associated with sleep deprivationSDfrom chronic sleep fragmentation or wake after sleep onsetWASOpoor sleep qualityetcand clinically significant daytime cognitive declineActivas DiagnosticsActivas Diagnostics comoffers a home basednonwearablemattress based sleep systemSleepMovedeveloped in clinical research and now is a patented biotechnologyOur sensor system provides standard actigraphy type sleep fragmentation indices with the value proposition that SleepMove mattress platform identifies high frequencysleep related movement arousalsi eno EEg changeMAAs part of arousal neurocircuitryMAs are deficient in sleep disorder and neurological diseaseOur previous work has shown that MAs are sleep related movementSMburstssecthat are periodicminwithin the window of asphyxiationIt is known that SD suppresses the arousal system during sleepPublished work with the SleepMove system has established that MAs are similarly reduced by SD and significantly reduced in patients with neurological conditionsIn a SleepMove pilot studydemographic control participants without SDageshowed MAs that were robustand triggered an increase in respiratory ratetermed SM RR couplingIn contrastMCI patients showed more SD and sleep fragmentationas well as deficient MA vigorand fewer and less efficient SM RR couplingSM RR coupling supports respiratory toneairway patencyand may moderate hypoxia risk during sleepThe design of the SleepMove mattress device integrates cutting edge sensor technologysignal processing and statistical inference software to identifydistinct signature biomarkers of SD that complement standard actigraphyand adds a novel parameter of respiratory function and modulation during sleeplong implicated in neurological declineMA measured through SMi eperiodicitypatterningand amplitudeand reflecting arousal tonesleep fragmentation and SDRR modulation through SM RR couplinga time series segmentation analysis of respiratory variability linked to MAsIn the proposed home based clinical studySD and cognitive declineas parameters of MCI severitywill be estimated in diagnosed MCI and control participants from SleepMove actigraphy and new SD indicatorsSM reductionand poor responsiveness of RR during SM RR coupling MA eventsThese novel physiological parameters are proposed correlates of poor sleepTo evaluate SleepMove predictive parametersan overnight memory consolidation test ofmin prevspost sleepepisodic and proceduralmemory consolidation testing followed by complete neuropsychological battery withindaysMCI diagnosed group will be compared to a demographicnonMCI comparison groupNageyearsreferred from two gerontology and aging centers participating in this studyParticipants living independently will be tested in the home with the Activas Diagnostics SleepMove mattress device fornights to collect SM and respiratoryRRtime seriesand standard actigraphy measures of sleep qualityOn nightmemory consolidation will be probed using aminautomated pre post sleepbrief memory app designed for easyhome use in cognitively challenged participantsSleep and memory data will be collected and transmitted wirelessly to the lab for analysis with our proprietary algorithmsNew diagnostic criteria for MCI and severity status will be developed using thresholding methods with ROCreceiver operating characteristicsstatistical method comparing sleep healthi eSMSM RR couplingsleep fragmentation and efficiency estimatesand sleep diary to the memory consolidation probe and neurocognitive batteryIn a parallel streamour commercialization effort will pursue appropriate professional staff to develop FDA and other regulatory solutions for ICDdesignation and insurance adoptiondevelop new strategic partnering in the medical device sleep business insurance communityand for business model scale up for Phase II goalsFuture applications include investigations of AD related dementias and other neurological disease Project Narrative This supplemental study will address Alzheimerandapos s diseaseADearly detection through examining depression in normal aging persons currently without diagnosis measured in the home environment uses a novel nonintrusive device and new metricsDiversity in the team will be enhanced for the areas of disabilitywomen in STEM and women in business through the project and mentorship of the candidate