In 2020, researchers found that a dysfunction in learning presents as a very large sign of Alzheimer’s disease (AD) related biology. Importantly, even when memory dysfunction can be detected in early AD, the magnitude is substantially smaller than the learning dysfunction observed. This observation opens an entirely new method for understanding clinical pathological relationships in preclinical AD.
Led by Dr. Yen Ying Lim (Turner Institute, Monash University) and Dr. Paul Maruff (Cogstate), the research team developed a novel test paradigm that required older adults to learn the English language terms for a set of 50 different Chinese characters. Analyses of the learning curves showed that in older adults with normal levels of amyloid, the acquisition of the novel information proceeded in accord with the learning curves described initially by Ebbinghaus with performance improving at a faster rate over initial learning trials and then becoming asymptotic at longer intervals.
Compared to healthy older adults, the preclinical AD group matched on age, sex and education levels showed that while learning of the Chinese characters did improve, the rate of learning was reduced substantially. These results were interpreted as indicating that in preclinical AD there is a reduced level to benefit from novel experience. This same learning dysfunction has now been observed in cognitively normal individuals whose risk for AD is increased (through carriage of ApoE4) but whose amyloid levels remain within normal limits.
There is now conjecture that disease-modifying therapies for AD may be most effective in the preclinical stages of the illness and therefore drug development programs are focusing on this stage of the disease. The large effects of amyloid observed on these learning paradigms over short time periods suggests they could be a useful cognitive challenge model for early phase studies seeking to understand the effects of drugs designed to improve cognition in AD.
Watch this webinar to hear an expert from Cogstate describe the methods the research team used and expound on the implications of these important findings. The presentation also provides commentary on what comes next in this ground-breaking research.
Paul Maruff, PhD
Chief Innovation Officer, Cogstate
Professor Paul Maruff is one of the founders of Cogstate and served as Chief Science Officer before taking on the role of Chief Innovation Officer. 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 in clinical medicine. Paul remains an active researcher. He is an appointed Professor at the Florey Institute for Neuroscience and Mental Health. He is currently clinical co-chair of the Australian Imaging Biomakers and Lifestyle (AIBL) study. Paul has published over 450 research articles in international peer-reviewed scientific journals and has co-authored 15 book chapters.