SBIR-STTR Award

Impairment in instrumental activities of daily living (IADL) is a hallmark of Alzheimer’s disease (AD) dementia and a major source of patient and caregiver burden. Similarly to cognitive changes in AD, subtle difficulties in IADL may begin even before the stage of amnestic mild cognitive impairment (MCI). Recently, greater emphasis has been placed on preclinical AD, which consists of individuals with minimal or no symptoms but biological marker evidence of AD pathology. As secondary prevention trials in preclinical AD are underway and the Food and Drug Administration (FDA) is providing new guidance for early-stage AD clinical trial outcome measures, it is imperative that we develop new ecologically valid instruments to be able to track the emergence of subtle yet clinically meaningful alterations in IADL. Older individuals are increasingly required to interact via the telephone, computer, and most recently smartphone, to perform essential IADL, such as refilling prescriptions, communicating with healthcare providers, and performing financial transactions. Most IADL tests do not use everyday technology and are insufficiently validated. The goal of this project is to complete the development of, optimize, and validate a novel performance-based IADL instrument that uses a smartphone to assess healthcare-related daily activities, the Assessment of Smartphone Everyday Tasks (ASSET). For Phase 1, during Year 1 of the award, we will first develop 5 alternate versions of ASSET. We will then recruit 20 cognitively normal young adults (YN), 20 cognitively normal older adults (CN), and 20 amnestic mild cognitive impairment (MCI) participants at a single site, the Center for Alzheimer Research and Treatment (CART) at Brigham and Women’s Hospital (BWH). Those 60 participants will undergo cognitive testing and ASSET in the research clinic. The 60 participants will then undergo short-interval (2 weeks) test-retest reliability of the 6 versions of ASSET (current version and 5 new alternate versions) remotely/at-home. For Phase 2, during Years 2 and 3 of the award, CART will serve as a coordinating center for 10 Alzheimer’s Disease Research Center (ADRC) sites, each of which will recruit 20 CN, 20 older adults with subjective cognitive decline, and 10 MCI participants for a total of 500 participants. Those participants will undergo the Uniform Data Set (UDS) neuropsychological testing battery as part of their ADRC annual visits, as well as the smartphone app tasks, ASSET, and a subjective questionnaire at baseline and 1 year later, and in between remotely at home, they will also perform ASSET on a monthly basis. Finally, AD pathology biomarker data (amyloid positron emission tomography or cerebrospinal fluid abeta positive/negative) available from other studies at the ADRC performance sites will be analyzed in about half of participants.

Public Health Relevance Statement:
Project Narrative The field is moving toward finding more sensitive clinical measures for early diagnosis and tracking of subtle changes over time that are associated with AD biomarkers but are easy and inexpensive to administer by primary care physicians, who are on the frontlines of the medical battle. Developing more sensitive, ecologically valid performance-based IADL tests like ASSET is vital to the goal of improving the tracking of individuals through the tipping point between preclinical AD and prodromal AD. ASSET has been designed to tap the high-level healthcare-related tasks that challenge seniors in daily life and are important to them, to serve as a clinically meaningful outcome measure for preclinical and prodromal AD trials, and to be easy and quick to administer remotely/at-home, using real-life devices.

Project Terms:
Alzheimer's Disease; Alzheimer's disease pathology; Alzheimer's disease related dementia; Alzheimer’s disease biomarker; amnestic mild cognitive impairment; Amyloid; Amyloid beta-Protein; Appointment; Award; base; Biological Markers; Boston; Businesses; Calendar; Caregiver Burden; Cellular Phone; Cerebrospinal Fluid; Clinic; Clinical; Clinical Trials; Cognitive; cognitive change; cognitive performance; cognitive testing; Computers; daily functioning; Data; Data Set; design; Development; Devices; digital; Early Diagnosis; Elderly; Emergency department visit; experience; functional decline; Future; Goals; Health Personnel; Healthcare; Home environment; Hospitals; Impaired cognition; Impairment; improved; Individual; instrument; instrumental activity of daily living; Life; Measures; Medical; mild cognitive impairment; Monitor; Multicenter Studies; Neuropsychological Tests; novel; Outcome Measure; Participant; patient portal; Patients; payment; Performance; performance site; Phase; Physical therapy; Physicians; Positron-Emission Tomography; pre-clinical; Prevention trial; Primary Care Physician; prodromal Alzheimer's disease; Questionnaires; recruit; Research; response; Schedule; Secondary Prevention; Site; smartphone Application; Source; Symptoms; System; Technology; Technology Transfer; Telephone; Testing; Time; Transact; United States Food and Drug Administration; Visit; Voice; Woman; young adult

Impairment in instrumental activities of daily living (IADL) is a hallmark of Alzheimer's disease (AD) dementiaand a major source of patient and caregiver burden. Similarly to cognitive changes in AD, subtle difficulties inIADL may begin even before the stage of amnestic mild cognitive impairment (MCI). Recently, greater emphasishas been placed on preclinical AD, which consists of individuals with minimal or no symptoms but biologicalmarker evidence of AD pathology. As secondary prevention trials in preclinical AD are underway and the Foodand Drug Administration (FDA) is providing new guidance for early-stage AD clinical trial outcome measures, itis imperative that we develop new ecologically valid instruments to be able to track the emergence of subtle yetclinically meaningful alterations in IADL. Older individuals are increasingly required to interact via the telephone,computer, and most recently smartphone, to perform essential IADL, such as refilling prescriptions,communicating with healthcare providers, and performing financial transactions. Most IADL tests do not useeveryday technology and are insufficiently validated. The goal of this project is to complete the development of,optimize, and validate a novel performance-based IADL instrument that uses a smartphone to assesshealthcare-related daily activities, the Assessment of Smartphone Everyday Tasks (ASSET). For Phase 1, during Year 1 of the award, we will first develop 5 alternate versions of ASSET. We will thenrecruit 20 cognitively normal young adults (YN), 20 cognitively normal older adults (CN), and 20 amnestic mildcognitive impairment (MCI) participants at a single site, the Center for Alzheimer Research and Treatment(CART) at Brigham and Women's Hospital (BWH). Those 60 participants will undergo cognitive testing andASSET in the research clinic. The 60 participants will then undergo short-interval (2 weeks) test-retestreliability of the 6 versions of ASSET (current version and 5 new alternate versions) remotely/at-home. For Phase 2, during Years 2 and 3 of the award, CART will serve as a coordinating center for 10 Alzheimer'sDisease Research Center (ADRC) sites, each of which will recruit 20 CN, 20 older adults with subjective cognitivedecline, and 10 MCI participants for a total of 500 participants. Those participants will undergo the Uniform DataSet (UDS) neuropsychological testing battery as part of their ADRC annual visits, as well as the smartphone apptasks, ASSET, and a subjective questionnaire at baseline and 1 year later, and in between remotely at home,they will also perform ASSET on a monthly basis. Finally, AD pathology biomarker data (amyloid positronemission tomography or cerebrospinal fluid abeta positive/negative) available from other studies at the ADRCperformance sites will be analyzed in about half of participants.

Public Health Relevance Statement:
Project Narrative The field is moving toward finding more sensitive clinical measures for early diagnosis and tracking of subtle changes over time that are associated with AD biomarkers but are easy and inexpensive to administer by primary care physicians, who are on the frontlines of the medical battle. Developing more sensitive, ecologically valid performance-based IADL tests like ASSET is vital to the goal of improving the tracking of individuals through the tipping point between preclinical AD and prodromal AD. ASSET has been designed to tap the high-level healthcare-related tasks that challenge seniors in daily life and are important to them, to serve as a clinically meaningful outcome measure for preclinical and prodromal AD trials, and to be easy and quick to administer remotely/at-home, using real-life devices.

Project Terms: