Shannon Finley

VALIDATION OF ONLINE DATA FROM IDEAS PARTICIPANTS WITH MCI AND AD USING THE BRAIN HEALTH REGISTRY

amyloid PET were better with in-clinic memory measures (0.360.61) than ARC Prices (0.31), a composite of ARC measures showed stronger correlations with both CSF tau (ARC 1⁄4 0.64 vs. in-clinic 1⁄4 0.25; Figure 2) and tau PET (ARC 1⁄4 0.41 vs. in-clinic 1⁄4 0.16). Conclusions: Extremely brief and frequent smartphone cognitive assessments demonstrate excellent reliability and are valid measures of cognition that are sensitive to AD biomarkers. These measures may be particularly sensitive to neurodegeneration in preclinical AD populations. Correlations between cerebrospinal fluid total-tau and ARC smartphone assessments and standard in-clinic assessments (n 1⁄4 30).

The Brain Health Registry: An internet-based platform for recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies

Recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies and clinical trials limit the development of new treatments. Widespread Internet use allows data capture from participants in an unsupervised setting. The Brain Health Registry, a website and online registry, collects data from participants and their study partners.

DUTCH ONLINE REGISTRY FOR RECRUITMENT OF PARTICIPANTS FOR DEMENTIA STUDIES: HERSENONDERZOEK.NL AND BRAIN HEALTH REGISTRY

Data are presented as mean6 SD or n (%). MCI, Mild cognitive impairment. Laurent Cleret de Langavant, Eleonore Bayen, Kristine Yaffe, Ecole Normale Sup erieure Paris Est University H Mondor Hospital, Creteil, France; Ecole Normale Superieure, Paris, France; Assistance Publique Hôpitaux de Paris Henri Mondor Hospital, Creteil, France; INSERM, Paris, France; University of California San Francisco Global Brain Health Institute, San Francisco, CA, USA, and Sorbonne Universit e La Pitie-Salpetriere, Paris, France; University of California, San Francisco, San Francisco, CA, USA. Contact e-mail: laurent.cleret@gbhi. org

Online study partner-reported cognitive decline in the Brain Health Registry

Methods for efficiently identifying cognitive decline and Alzheimers disease (AD) are a critical unmet need. The goal of this work was to validate novel online study partner (SP)‐reported outcomes to identify cognitive decline in older adults.

Unsupervised online neuropsychological test performance for individuals with mild cognitive impairment and dementia: Results from the Brain Health Registry

The purpose of this study is to compare online neuropsychological test performance of older adults across self‐reported diagnoses of being cognitively normal, mild cognitive impairment, and dementia due to Alzheimers disease and to determine the association of memory concerns and family history of dementia on cognitive performance.

VALIDATION OF A COMPUTERIZED NEUROPSYCHOLOGICAL TEST BATTERY INCLUDING VERBAL MEMORY USING SPEECH RECOGNITION SOFTWARE

performance in the smooth pursuit task. This model validation allows descriptions of individual patients’ data, as compared to a healthy control, to be made with confidence. Identifying areas of their sequences that either conform to or deviate from a healthy performance can provide valuable insight into an individual’s basic oculo-motor function. Subject to further validation from more data, the classification procedure could form the basis of a noninvasive automatic diagnostic tool for dementia.

THE DUTCH BRAIN HEALTH REGISTRY: OPTIMIZING RECRUITMENT FOR DEMENTIA RESEARCH

Background: Muscarinic M1 receptor (M1R) is a promising target for CNS disorders with cholinergic deficits such as Alzheimer’s disease. We previously reported that the cooperativity (a-value) was a key to lower the risk of diarrhea by M1R positive allosteric modulators (M1PAMs). In this study, we characterized in vitro profiles of TAK-071, a novel M1R selective PAM with a low a-value and compared with that of T-662, an M1PAM with a high a-value. Methods:PAM parameters were assessed by using in vitro binding and functional analysis in Chinese hamster ovary cells stably expressing human M1R. Evaluation of mouse ileum contraction was conducted under the conditions to assess spontaneous activity or electric field stimulation (EFS)-induced activity by using the in vitro Magnus method. Electrophysiological experiments were performed by using current clamp recordings in slices of mouse medial prefrontal cortex. Results:TAK-071 had an inflection point (IP)-value of 2.7 nM, and showed an a-value of 199 for humanM1R with more than 3700-fold selectivity over other muscarinic receptor subtypes. T-662 also had potent M1PAM activity with an IP-value of 2.1 nM, and showed an a-value of 1786. In the in vitro Magnus method, T-662, but not TAK-071, strengthened spontaneous ileum contraction in a concentration-dependent manner, and augmented EFS-induced ileum contraction. Tonic activation of M1Rs is known to produce neuronal excitability through three actions; depolarizing the resting membrane potential, suppressing the after hyperpolarization that follows the spike, and revealing the afterdepolarization (ADP) that can initiate repetitive firing. Among then, T-662 induced all three actions, while TAK-071 selectively induced ADP in layer 5 pyramidal neurons. Conclusions: We searched M1PAMs with low a-value and discovered TAK-071. TAK-071 induced ADP in layer 5 pyramidal neurons, while it did not cause mouse ileum contraction in vitro. Thus, TAK-071may have a promising therapeutic potential for CNS disorders without causing diarrhea. TAK-071 is currently in clinical development (ClinicalTrials. gov, Identifier: NCT02769065). total number of participants 297

Internet-based recruitment of subjects for prodromal and secondary prevention Alzheimer's disease trials using the brain health registry

O1-10-06 INTERNET-BASED RECRUITMENT OF SUBJECTS FOR PRODROMAL AND SECONDARY PREVENTION ALZHEIMER’S DISEASE TRIALS USING THE BRAIN HEALTH REGISTRY Rachel L. Nosheny, Derek Flennkiken, Philip S. Insel, Shannon Finley, Scott Mackin, Monica Camacho, Diana Truran-Sacrey, Paul Maruff, Michael W. Weiner, San Francisco Veteran’s Administration Medical Center, San Francisco, CA, USA; San Francisco Veteran’s Administration Medical Center, San Francisco, CA, USA; UCSF, San Francisco, CA, USA; Center for Imaging ofNeurodegenerativeDiseases, SanFrancisco, CA,USA; CogstateLtd.,Melbourne,Australia; University of California San Francisco, San Francisco, CA, USA. Contact e-mail: rachel.nosheny@ucsf.edu