Clinical Outcome Assessments in Preclinical Alzheimer’s Disease: Considerations for Global Clinical Trials

Preclinical Alzheimer’s disease (AD) is classified in individuals who show abnormal levels of amyloid, tau or neurodegenerative biomarkers but who do not meet any clinical criteria for dementia or mild cognitive impairment. Current estimates indicate that this preclinical AD stage can last for more than 10 years and so it provides a unique opportunity to understand the clinical-pathological sequelae of very early AD. This information can be used to develop and implement therapeutic strategies that can slow or even halt these processes, so as to forestall the development of symptoms.

While individuals in the preclinical stage are, by definition, “cognitively unimpaired”, it may still be possible to observe change and decline in cognition. Meta-analyses show that in cognitively normal older adults with high amyloid-beta (Aβ) there is a subtle impairment in cognition, across multiple domains with the most robust occurring for episodic memory (Baker et al, 2016). In contrast, prospective studies show adults who meet clinical criteria for preclinical AD do show subtle but relentless decline in cognition, mainly episodic memory, loss of brain volume, further accumulation of AD biomarkers and higher rates of progression to mild cognitive impairment or dementia.

Clinical trials designed to study interventions at the preclinical AD stage are using fit-for-purpose clinical outcome assessments that have high validity and reliability for the detection of cognitive change at this early stage of the illness. This has led to the development of novel cognitive, functional and patient-reported outcomes specifically designed for early-stage disease, such as the PACC, C3, Amsterdam iADL Questionnaire, Cognitive Function Instrument and others. These assessments have novel requirements for their delivery that differ markedly from the conventional instruments used in trials conducted for mild cognitive impairment and dementia.

This free webinar will outline critical considerations in the application of preclinical stage instruments into industry clinical trials, including those that become important as studies are longer in duration and are conducted across various regions of the world.

Speakers

Paul Maruff, Chief Science Officer, Cogstate

Professor Paul Maruff is one of Cogstate’s founders. He is a neuropsychologist with expertise in the identification and measurement of subtle behavioral and cognitive dysfunction. Paul’s research integrates conventional and computerized neuropsychological testing with cognitive neuroscientific methods to guide decision-making in drug development and clinical medicine. He has worked extensively on methods to identify subtle neurocognitive impairment and assess the efficacy of pharmacological treatment in AD, mild cognitive impairment and the HIV dementia complex. He has extended this approach to identify cognitive dysfunction and monitor treatment efficacy in psychiatric diseases such as schizophrenia, obsessive-compulsive disorder and depression in adults, as well as attention deficit disorder, developmental dyspraxia and substance abuse in children. Paul is an active researcher, appointed professor at the Florey Institute for Neuroscience and Mental Health. He is currently clinical co-chair of the Australian Imaging Biomarkers and Lifestyle (AIBL) study. Paul has published over 250 research articles in international peer-reviewed scientific journals and has co-authored 10 book chapters.

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Edward Bartolic, PhD, Senior Science Director, Cogstate

Edward Bartolic is a clinical neuropsychologist with more than 20 years of postdoctoral clinical research experience in various scientific positions within global contract research organizations (CROs) prior to joining Cogstate in 2014, including director of CNS Research, scientific director for the rater training services department at i3 Research and director of clinical assessment technologies at Worldwide Clinical Trials. Dr. Bartolic has functioned as clinical/therapeutic lead, providing oversight of the development and management of global rater training and data monitoring/rater surveillance programs for studies in psychiatry and neurology. He has served as lead rater trainer at numerous investigators meetings for studies in indications that include AD, mild cognitive impairment/prodromal AD, MS, major depressive disorder, bipolar disorder‑mania, bipolar depression, schizophrenia and generalized anxiety disorder. He has designed customized methodologies for remote monitoring of clinical trial assessments, including review of source documentation and assessment results for verification of study eligibility criteria during the screening period and confirmation of proper administration and scoring of cognitive and other neurobehavioral assessments. He also has the unique experience of having coordinated and managed two different committees of independent clinical neurologists and geriatric psychiatrists responsible for adjudicating investigator-determined progression to AD endpoints in prodromal AD/mild cognitive impairment trials. Prior to working in the pharmaceutical industry, Dr. Bartolic served as assistant professor psychiatry at the Medical College of Pennsylvania and Hahnemann University in Philadelphia. He was also the director of neuropsychology at the Medical College of Pennsylvania Hospital and the Eastern Pennsylvania Psychiatric Institute, leading an active inpatient and outpatient clinical service and supervising neuropsychology students, interns and post-doctoral fellows.

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Chris Edgar, Senior Vice President, Clinical Science, Cogstate

Dr. Chris Edgar has an extensive background in the application of clinical outcome assessments (COAs) in drug development and has worked in the pharmaceutical industry for the past 17 years. He is the former scientific director of Cognitive Drug Research Ltd., the developers of CDR System, one of the earliest computerized cognitive test systems to be widely employed in clinical trials. Chris also has a background in COA management and rater training delivery with Bracket/UBC, and CNS/neuroscience clinical trial design and outcomes research with SHGVP and as an independent consultant. Chris is a psychologist with expertise in clinical trials methodology, COA implementation and related regulatory science topics. Chris’ research seeks to carefully define and apply clinical endpoints to answer key questions throughout the clinical development plan and product lifecycle. Chris has published over 20 research articles in international peer-reviewed scientific journals.

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