Presentations

Read research from Cogstate scientists as presented at industry conferences.

Initial exploration of a brain age score based on validated computerized cognitive assessments in Japanese individuals

Presented at AAIC 2020

Cognitive and/or neuropsychological tests typically have abstract outcome measures, where the clinical meaning of scores is not readily apparent. For clinicians, this is commonly achieved through an understanding of the normal distribution of scores, for example bone density t-scores in evaluating osteoporosis. This may not be well understood by patients and study participants though, and here the concept of being ‘normal for one’s age’ may also be valuable. A difference between chronological age and biological age has been used to more easily communicate health related information. Our team aimed to develop a ‘Brain Age’ score for communicating cognitive test performance.

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Using imputation to harmonize longitudinal measures of cognition across two large cohorts: AIBL and ADNI

Presented at AAIC 2020

To ensure the generalizability of findings and consider more nuanced hypotheses, larger sample sizes are required. Combining data from different but similar study cohorts is one solution. However, the disparity of these datasets, e.g. using differing tests to assess specific cognitive domains, makes this a non-trivial task. Here, we propose a harmonization solution using imputation strategies for cognitive memory performance in AIBL2 and ADNI3.

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Plasma Aβ biomarker associated with cognitive decline in preclinical Alzheimer’s disease

Presented at AAIC 2020

We recently showed in two independent cohorts, that a plasma Aβ composite biomarker, which was generated by combining plasma ratios of APP 669 711 /Aβ 1 42 and Aβ 1 40 /Aβ 1 42 as measured by immunoprecipitation mass spectrometry (IP-MS) assay, had very high areas under the receiver operating characteristic curves (AUCs) (94-96%), with an accuracy of ~90% for the classification of high Aβ levels based on Pittsburgh Compound B PiB PET. This plasma Aβ composite biomarker may therefore have great clinical utility for predicting Aβ levels. We aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts.

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Development of the Snellen Memory Test (SMT): An episodic memory test to screen for AD risk in a clinical optometry/ophthalmology setting

Presented at AAIC 2020

Retinal biomarkers are an ideal target for AD risk biomarker development: the retina shares neurobiology and neurochemistry with the central nervous system (CNS), and can be visualized using standard optometry and ophthalmology techniques. Retinal imaging using spectral domain optical coherence tomography (SD-OCT) is minimally invasive, cost-effective, highly accessible, and can be implemented by point-of-care clinicians in clinical optometry and ophthalmology practices. Because many adults over the age of 40 regularly see an eye-care professional for routine care and prescription adjustments for corrective lenses, assessment of AD risk in clinical optometry practice provides an ideal opportunity for high volume screening of large portions of the population.

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HOPE4MCI Trial: First Trial Targeting Reduction of Hippocampal Overactivity to Treat Mild Cognitive Impairment due to Alzheimer’s Disease with AGB101

Presented at AAIC 2020

Evidence from preclinical models and human patients demonstrates that neuronal circuits become hyperactive in prodromal AD contributing to the accumulation of Alzheimer’s pathology and subsequent cognitive decline. Such data support the hypothesis that neural overactivity in the medial temporal lobe/hippocampus is a critical driver of AD neuropathology, including the deposition of amyloid and spread of tau along connectional pathways. AGB101 (low dose levetiracetam) demonstrates efficacy on a range of molecular, synaptic, electrophysiological, functional and behavioral endpoints across models and species. In a Phase 2 study measuring hippocampal activity during a pattern separation memory test in patients with aMCI, AGB101 normalized hippocampal activity and improved performance on this specific memory assessment of hippocampal function. The HOPE4MCI trial is investigating the effects of AGB101 (220 mg) vs placebo in patients with MCI due to AD.

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The Cogstate Schizophrenia Battery (CSB) as a Co-Primary Outcome for Trials in Cognitive Impairment Associated with Schizophrenia

Presented at SIRS 2020

Extensive evidence shows cognitive impairment to be a core symptom of schizophrenia that has a negative impact on function. The MATRICS/FDA/NIMH workshop developed guidelines for the design of clinical trials of drugs that could ameliorate cognitive impairment associated with schizophrenia (CIAS). One important consequence was the development of a battery of performance based (PerfO) outcome assessments. The use of the MATRICS Consensus Cognitive Battery (MCCB) as a co primary outcome is recommended by FDA, whilst EMA describe the battery as “acceptable but other, comparable, test batteries may also be used provided their validity is demonstrated”. Following the development an application of the MCCB, substantial concerns have been raised regarding patient and trial burden, and cross-cultural adaptability. In this context, the Cogstate Schizophrenia Battery (CSB) has been developed as a computerized cognitive test battery, meeting consensus requirements, but with significantly reduced burden on patients and clinical trial sites.

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Utility of the Cogstate Brief Battery for In-clinic and At-home Cognitive Assessments in ADNI-3

Presented at AAT-AD/PD 2020

The Cogstate Brief Battery (CBB) is a computerized/digital cognitive test battery assessing psychomotor function, visual attention, visual learning, and working memory. The CBB takes approximately 15 minutes to complete, has been optimized for self-completion, and is offered to cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-3 and those rolling over from ADNI-2. In-clinic visits are completed annually for MCI and every other year for CN participants, with both groups completing unsupervised visits at-home approximately every 3 months.

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Clinical Outcome Assessments for Clinical Trials in Rare Tauopathies

Presented at AAT-AD/PD 2020

Tauopathies may be classified by neuropathological phenotype. Clinically, PSP, CBD, MSA and DLB may be grouped as atypical parkinsonism; FTLD distinguished by behavioral, language and MND variants; and AGD, PART and ARTAG are hard to distinguish from AD. Thus, overlapping measurement concepts exist for clinical outcome assessments (COAs).

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Considerations for the Generalizability of Clinical Outcome Assessment Validation Data Across Rare Diseases

Presented at RARE Patient Advocacy Summit 2019

Development, validation and selection of clinical outcome assessments (COAs) requires, clear understanding of concepts of interest (COIs) for measurement and intended context of use (COU), evidence for content validity and evidence for psychometric validity and reliability. The ability to reuse or adapt existing COAs for novel COUs is valuable in reducing cost and timelines. In rare disease, availability of patients and issues of disease course and severity may make adaptation an imperative.

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Effect of Esketamine Nasal Spray on Cognition in Patients With Treatment-Resistant Depression: Results From Five Phase 3 Studies

Presented at ECNP 2019

Major depressive disorder (MDD) is a debilitating psychiatric illness and is a major contributor to the overall global burden of disease. Nearly one-third of patients with MDD do not respond to available antidepressants (AD) and develop treatment-resistant depression (TRD). The growing prevalence of TRD and the poor response rates to ADs4 , highlight the need for novel treatments that can provide rapid and sustained relief of depressive symptoms in patients with TRD. Esketamine (ESK), the S-enantiomer of ketamine, is an N-methyl-D-aspartate (NMDA) receptor antagonist recently approved by the US FDA as a nasal spray, along with a newly administered oral AD, for therapy of TRD.

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