In the JournalsPerspective

Experts urge new research framework to redefine Alzheimer’s disease

Maria C. Carrillo, PhD
Maria C. Carrillo
 

Experts are pushing for a new research framework that shifts the definition of Alzheimer’s disease from one based on cognitive changes and behavioral symptoms confirmed by biomarkers to a biological construct.

Researchers hope that defining Alzheimer’s disease by biological changes in the brain associated with Alzheimer’s disease will lead to a more accurate understanding of the progression of events that lead to cognitive impairment, according to a paper published in Alzheimer’s & Dementia.

"With the aging of the global population, and the ever-escalating cost of care for people with dementia, new methods are desperately needed to improve the process of therapy development and increase the likelihood of success," Maria C. Carrillo, PhD, chief science officer of the Alzheimer's Association, said in a press release. "This new Research Framework is an enormous step in the right direction for Alzheimer's research."

The National Institute on Aging and Alzheimer’s Association (NIA-AA) published separate diagnostic recommendations in 2011 for the preclinical, mild cognitive impairment and dementia stages of Alzheimer’s disease. However, progress and changes in Alzheimer’s disease research have prompted the NIA-AA to commission experts to update the guidelines for observational and interventional research, not for clinical care.

The new research framework focusses on diagnosing Alzheimer’s disease with biomarkers — which are grouped into those of beta amyloid deposition, pathologic tau and neurodegeneration — in living people using imaging and cerebral spinal fluid samples. It also emphasizes the incorporation of severity measures using biomarkers and a grading system for cognitive impairment, according to a second press release. Specifically, it concentrates on Alzheimer’s disease as a continuum and outlines two categorical cognitive schemes for presenting the severity of cognitive impairment: one using three traditional syndromal categories and a one using a six-stage numeric structure, according to the authors.

"We have to focus on biological or physical targets to zero in on potential treatments for Alzheimer's," Eliezer Masliah, MD, director of the Division of Neuroscience at the NIA, said in a press release. "By shifting the discussion to neuropathologic changes detected in biomarkers to define Alzheimer's, as we look at symptoms and the range of influences on development of Alzheimer's, I think we have a better shot at finding therapies, and sooner."

According to the researchers, this framework seeks to create a common language that researchers can use to create and test theories about the interactions of different cognitive symptoms and pathologic processes signified by biomarkers. They highlight that this research framework should not be used yet in general medical practice nor to limit alternative testing approaches that do not use biomarkers.

"In the context of continuing evolution of Alzheimer's research and technologies, the proposed research framework is a logical next step to help the scientific community advance in the fight against Alzheimer's," Richard J. Hodes, MD, director of the NIA, said in a press release. "The more accurately we can characterize the specific disease process pathologically defined as Alzheimer's disease, the better our chances of intervening at any point in this continuum, from preventing Alzheimer's to delaying progression.” – by Savannah Demko

Disclosures: Healio Psychiatry was unable to confirm relevant financial disclosure at the time of publication.

Maria C. Carrillo, PhD
Maria C. Carrillo
 

Experts are pushing for a new research framework that shifts the definition of Alzheimer’s disease from one based on cognitive changes and behavioral symptoms confirmed by biomarkers to a biological construct.

Researchers hope that defining Alzheimer’s disease by biological changes in the brain associated with Alzheimer’s disease will lead to a more accurate understanding of the progression of events that lead to cognitive impairment, according to a paper published in Alzheimer’s & Dementia.

"With the aging of the global population, and the ever-escalating cost of care for people with dementia, new methods are desperately needed to improve the process of therapy development and increase the likelihood of success," Maria C. Carrillo, PhD, chief science officer of the Alzheimer's Association, said in a press release. "This new Research Framework is an enormous step in the right direction for Alzheimer's research."

The National Institute on Aging and Alzheimer’s Association (NIA-AA) published separate diagnostic recommendations in 2011 for the preclinical, mild cognitive impairment and dementia stages of Alzheimer’s disease. However, progress and changes in Alzheimer’s disease research have prompted the NIA-AA to commission experts to update the guidelines for observational and interventional research, not for clinical care.

The new research framework focusses on diagnosing Alzheimer’s disease with biomarkers — which are grouped into those of beta amyloid deposition, pathologic tau and neurodegeneration — in living people using imaging and cerebral spinal fluid samples. It also emphasizes the incorporation of severity measures using biomarkers and a grading system for cognitive impairment, according to a second press release. Specifically, it concentrates on Alzheimer’s disease as a continuum and outlines two categorical cognitive schemes for presenting the severity of cognitive impairment: one using three traditional syndromal categories and a one using a six-stage numeric structure, according to the authors.

"We have to focus on biological or physical targets to zero in on potential treatments for Alzheimer's," Eliezer Masliah, MD, director of the Division of Neuroscience at the NIA, said in a press release. "By shifting the discussion to neuropathologic changes detected in biomarkers to define Alzheimer's, as we look at symptoms and the range of influences on development of Alzheimer's, I think we have a better shot at finding therapies, and sooner."

According to the researchers, this framework seeks to create a common language that researchers can use to create and test theories about the interactions of different cognitive symptoms and pathologic processes signified by biomarkers. They highlight that this research framework should not be used yet in general medical practice nor to limit alternative testing approaches that do not use biomarkers.

"In the context of continuing evolution of Alzheimer's research and technologies, the proposed research framework is a logical next step to help the scientific community advance in the fight against Alzheimer's," Richard J. Hodes, MD, director of the NIA, said in a press release. "The more accurately we can characterize the specific disease process pathologically defined as Alzheimer's disease, the better our chances of intervening at any point in this continuum, from preventing Alzheimer's to delaying progression.” – by Savannah Demko

Disclosures: Healio Psychiatry was unable to confirm relevant financial disclosure at the time of publication.

    Perspective
    John Ringman

    John Ringman

    In this paper the authors, representing academia, the Alzheimer’s Association (AA) and the National Institute of Aging (NIA), present a summary statement describing the effort to re-conceptualize Alzheimer’s disease purely as a biological process. Traditionally, we have defined Alzheimer’s as a clinical syndrome associated with specific changes occurring in the brain; the amyloid plaques and neurofibrillary tangles consisting of tau protein. This clinical syndrome is typically characterized by memory problems occurring in the elderly that progress to affect other aspects of thinking, behavior and, ultimately, self-care. However, it is now well-established that many persons with the classic Alzheimer’s syndrome do not have Alzheimer’s pathology in their brain and that, on the other hand, some people with Alzheimer’s pathology in their brain have no or only atypical symptoms.

    In light of this, in 2011 the NIA and AA convened panels to create criteria for three distinct stages of the Alzheimer’s disease (AD) process based on clinical symptoms and biological markers of the neuropathology. Specifically, over the last 15 to 20 years we have identified imaging changes in the brain using positron emission tomography (PET) techniques and biochemical changes in the cerebrospinal fluid that more directly represent these biological processes.

    In the current paper the committee takes these developments in AD biomarkers to the next step and propose, at least in a research context, to not use the term Alzheimer’s, but rather to characterize persons on a continuum in terms of the presence or absence of biomarkers suggestive of amyloid plaques, tau pathology and other evidence of neurodegeneration. They indicate that this approach will facilitate research into disease mechanisms and clinical trials of interventions, particularly those targeting disease prevention. They emphasize that this approach does apply to the clinical context in which the term Alzheimer’s is still useful, and they do not intend to exclude other avenues of AD research that do not involve biomarkers.

    This paper does not present any new findings but rather is a summary of the general direction Alzheimer’s research has been taking over the last 15 years and outlines a way to approach research in Alzheimer’s going forward.

    • John Ringman, MD, MS
    • Professor of clinical neurology Keck School of Medicine University of Southern California

    Disclosures: Ringman reports no relevant financial disclosures.

    Editor’s Note: This story has been updated to reflect a revision from the perspective author.