Computerized tests of cognitive decline in presymptomatic Alzheimer's disease

Patients who develop Alzheimer s diseaseADshow performance declines in tests of episodic memoryexecutive functioningand attention more than a decade before symptoms become apparent to their physician or familyThe rate of this performance decline is the primary outcome measure in ongoing clinical trials evaluating interventions aimed at delaying AD onsetHowevercurrent clinical trials rely on measures frompaper and penciltests of cognition that are manually administered and scoredcostlyinefficientsubject to examiner biasand fail to comprehensively record and quantify test performanceMoreoverbecause of the limited number of licensed examinersmanual tests will be increasingly unable to meet the demand for cognitive assessments as the population agesAlthough computerized tests help meet this demand by increasing the sensitivityefficiencycomprehensivenessand objectivity of cognitive testingexisting commercial test batteries lack the sensitivityvalidityand reliability ofgold standardmanual assessments now used in clinical trialsIn thisfast trackapplicationwe propose to enhance the computerized tests of the California Cognitive Assessment BatteryCCABa set of empirically validatedcomputerized versions ofgold standardmanual testsCCAB tests are more efficientreliableobjectiveand precise than their manual test counterpartswhile providing more detailedcomprehensiveand easily accessible archival records of longitudinal test performanceWe will then test the enhanced CCAB s sensitivity to longitudinal cognitive decline in older individualsincluding those at increased risk of cognitive decline based on their APOE genotypeDuring Phase Iwe will restructure the individual CCAB tests for self administration on tablets and add automatic speech recognition to objectively score verbal responses and measure verbal response latenciesWe will also incorporate telemedical capabilities to enable examiners to interact with patients and administer tests at remote sitesDuring Phase IIwe will develop a secureencrypted database for hosting and analyzing anonymized dataWe will compare performance on CCAB tests and equivalent manual testsand develop regression functions for translating CCAB scores to equivalent manual test scoresand vice versaFinallywe will evaluate the sensitivity of the CCAB tests to cognitive decline inolder paid volunteerstested at six month intervals over a two year periodWe will identify baseline performance measuresincluding practice effectsincidental improvements that occur when tests are repeatedthat predict subsequent cognitive decline in individuals with and without genotype risk factors for ADIn additionwe will create CCAB licensing and data management tools to provide researchers with free access to CCAB tests and anonymized data during theyear SBIRSummaryEnhanced versions of the California Cognitive Assessment BatteryCCABwill reduce the costexpand the reachand improve the sensitivity of tests of agerelated cognitive decline in patients at risk for AD Project NarrativeAlzheimer s disease is a health care burden with enormous medical and personal cost that will affect an increasing number of Americans as the population agesCognitive testing plays a central role in identifying at risk patientsdeclines in cognitive tests of memory and other mental functions can be detected long before the onset of dementiaMoreoverthe success of clinical trials for new therapies designed to reverse Alzheimer s pathology and slow cognitive decline depends on the sensitivity of the tests used to detect cognitive deteriorationThe cognitive tests currently used are mostlypaper and pencilassessments that require manual administrationWe propose to develop a set of innovativecomputerized cognitive tests with greater sensitivity and reliability than manual testsand demonstrate their increased sensitivity to cognitive decline by repeatedly testing a large group of older individualsincluding some with increased genetic risk for Alzheimer s disease