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Cogstate Scientists Contribute to New Research Framework to Redefine Alzheimer’s Disease

April 17, 2018

new research framework for understanding Alzheimer’s disease has been developed and released by the Alzheimer’s Association (AA) and the National Institute on Aging (NIA).  This framework proposes an important shift in the definition of Alzheimer’s disease from being founded on the presence and nature of symptoms to one based on the identification and characterization of pathologic changes in the brain.  Thus, the new framework considers cognition as a symptom of AD related pathological changes, rather than its defining feature.

Among the authors of the NIA-AA Research Framework are Cogstate Distinguished Medical Adviser, Dr. Eric Siemers, MD, and Cogstate Chief Science Officer, Prof Paul Maruff. According to the authors “the goal of much of medicine is to identify and treat diseases prior to overt symptoms. The framework is intended to provide a path forward to … prevention trials of Alzheimer’s disease among persons who are clinically asymptomatic.”

The NIA-AA framework proposes a more precise staging of patients along the Alzheimer’s disease continuum and updates the diagnostic guidelines developed by the same organization in 2011 for defining the preclinical, mild cognitive impairment, and dementia stages of the disease. By establishing a common language for research, the framework serves as a tool to speed and improve the identification and development of disease-modifying treatments for Alzheimer’s disease by enabling a more targeted approach to clinical trials, including the use of more specific patient populations.

Dr. Eric Siemers commented, “The new NIA-AA Research Framework emphasizes the continuum of AD, and thus acknowledges the appearance of amyloid plaques prior to the onset of clinical symptoms. The earliest clinical symptoms of AD are likely to be most evident using sensitive measures of neuropsychological performance.”

Paul Maruff, Chief Science Officer at Cogstate, and also a member of the NIA-AA working group, commented that this new definition is a result of research arising from an expanded understanding of how AD related cognitive changes are associated with both the presence of, and changes in, amyloid, tau and brain volume loss. Prof Maruff stated, “Our own work in the Australian Biomarkers and Lifestyle (AIBL) study showed that episodic memory, measured using instruments such as the Cogstate battery, declined subtly but relentlessly in adults with abnormally high levels of amyloid, who were classified as cognitively normal. Similar observations were made in prospective studies conducted at the Mayo Clinic, University of Wisconsin-Madison, Harvard and in the Alzheimer’s Disease Neuroimaging (ADNI) study. Data from these studies converge to indicate that while abnormal levels of amyloid are a necessary condition for cognitive decline, the nature and magnitude of this decline is associated most strongly with loss of brain volume and requires the presence of abnormally high tau.”

These clinical pathological relationships therefore suggest that slowing amyloid or tau accumulation or neurodegeneration are all potential treatment targets for AD therapies. Furthermore, the clinical consequences of such strategies can be determined by their effects on the nature and rate of cognitive decline. Neuropsychological tests, including those from the Cogstate battery have been well validated to measure such changes.

Review the full release from the Alzheimer’s Association and National Institute on Aging, or review the full text publication.