Define Alzheimer’s by brain changes, not symptoms: experts

In an effort to speed research toward a cure for the most common form of dementia, experts urged a new framework Tuesday to diagnose Alzheimer’s disease using biological clues, rather than symptoms of memory loss.

Alzheimer’s affects some 44 million people around the world, but remains poorly understood, with no effective treatments despite billions of dollars spent on research.

Clinical trials have stumbled, with recent research showing that up to 30 percent of participants trying experimental drugs did not have the Alzheimer’s disease-related brain change targeted by the medicine.

The new approach would test for Alzheimer’s based on a few known biomarkers, and recognize that the disease runs on a spectrum that takes root long before symptoms appear, sometimes even for decades.

“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,” said Alzheimer’s Association chief science officer Maria Carrillo.

The proposed research framework is published in the April 10 edition of Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

The approach has been developed in recent years by 20 academic, advocacy, government and industry experts in dementia research, convened by the Alzheimer’s Association and the US National Institute on Aging (NIA).

In 2011, experts designated three stages of Alzheimer’s: preclinical (before symptoms affecting memory, thinking or behavior can be detected), mild cognitive impairment and dementia.

In 2017, international leaders convened again to review the latest advances in the field and update guidelines.

In the interim, “a profound shift in thinking occurred to define Alzheimer’s disease biologically, by pathologic brain changes or their biomarkers, and treat cognitive impairment as a symptom/sign of the disease, rather than its definition,” said the report.

Biomarkers are already widely used in medicine to diagnose people with high blood pressure, diabetes and bone density problems — and to reduce the likelihood of heart attack, stroke and bone fractures.

– ‘Logical next step’ –

“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,” said NIA director Richard Hodes.

“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.”

People can now be assessed for signs of Alzheimer’s using imaging technology and analysis of cerebral spinal fluid samples.

The NIA-AA research framework proposes three general groups of biomarkers that are currently known to science, and leaves room for more to be added in the future.

The first is beta-amyloid, a naturally occurring protein that accumulates in the brain, forming plaques.

The second is a protein called tau, which forms tangles that block communication between neurons.

The third is neurodegeneration or neuronal injury, which may result from aging, trauma or Alzheimer’s disease.

Experts cautioned that the framework is not intended to be a guideline for doctors or a checklist for diagnosis, but rather a path for researchers to follow.

“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,” said the NIA’s Eliezer Masliah.

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