Following recommendations by expert groups in the US, criteria for diagnosing Alzheimer’s disease, which have not changed in the last 25 years, will be updated to reflect scientific advances; the new guidelines will cover earlier stages and biomarkers of the disease.

A workgroup of the US National Institute of Neurological Disorders and Stroke (NINDS)/Alzheimer’s Disease and Related Disorders Association (ADRDA) established the current criteria back in 1984, and these have been more or less universally adopted since then as the “bible” for diagnosis.

Now, three working groups convened by the US National Institute on Aging (NIA) at the National Institutes of Health (NIH) and the Alzheimer’s Association, have drafted an updated set of criteria, and presented them to the Alzheimer’s Association International Conference on Alzheimer’s Disease 2010 (AAICAD 2010) in Honolulu, Hawaii on July 13.

In a statement to the press, Dr Creighton H. Phelps, Director of the Alzheimer’s Disease Centers Program in the NIA’s Division of Neuroscience, said:

“Important scientific discoveries have been made in Alzheimer’s, and there have been significant changes in our knowledge and conception of the disease.”

“The NIA and the Alzheimer’s Association, after consultation with the Alzheimer’s scientific and medical community, concluded that the diagnostic criteria may need to be revised to incorporate scientific advances.”

Dr William Thies, Chief Medical and Scientific Officer at the Alzheimer’s Association, explained that the proposed changes to the 1984 criteria would better reflect the various stages of the disease and include biomarkers, but cautioned that:

“While the role of biomarkers differs in each of the three stages, much remains to be understood concerning their reliability and validity in diagnosis.”

“This makes it critical that we thoroughly test any new recommendations,” he stressed.

Phelps said they formed three workgroups to examine the literature and make recommendations. One workgroup covered Alzheimer’s disease dementia, another covered mild cognitive impairment (MCI) due to Alzheimer’s disease, and the third covered preclinical Alzheimer’s disease.

The pre-clinical group has laid out a research agenda to identify ways to assess Alzheimer’s to help predict risk of developing the disease. This covers investigating biomarkers and other clinical assessment tools to spot early cognitive decline, the presence of brain changes in people with no overt symptoms and to identify those who may eventually develop the disease.

The MCI group is refining the criteria for MCI to better spot cognitive change before dementia and to better differentiate MCI from Alzheimer’s. Research into how cognitive change may relate to biomarkers, and which methods are most likely to spot imminent progression to Alzheimer’s dementia is already under way.

The Alzheimer’s dementia group is revising the existing criteria for diagnosing Alzheimer’s so it also covers possible biomarkers and other diagnostic aids.

The leaders of the three workgroups presented early drafts of their findings and recommendations to the AAICAD 2010 Conference, in order to get feedback and comments from the Alzheimer’s community.

Important discoveries and advances in the Alzheimer’s field since the 1984 criteria were drafed include:

  • In addition to cognitive function slowly declining over many years, Alzheimer’s is also accompanied by changes in the brain, until eventually the end stage of dementia: but not everyone who has the brain changes associated with the disease develops dementia.

  • Genes that predict early onset Alzheimer’s indicate that disordered beta amyloid metabolism is the first of the brain processes that lead to pathological changes in the brain and clinical signs of the disease.

  • The e4 variant of the APOE gene is now considered a major genetic risk factor for late onset (65 or older) Alzheimer’s disease.

  • At least four biomarkers of the disease have now been developed and are being validated, including biomarkers of beta amyloid pathology, neuronal injury, neuronal dysfunction, and neurodegeneration.

  • Differences and overlaps between Alzheimer’s and non-Alzheimer’s dementia are better understood (eg Alzheimer’s and cerebrovascular disease often co-exist).

Dr Guy McKhann, of John Hopkins University School of Medicine, chairs the working group revising the criteria for Alzheimer’s disease dementia. He told the media that the proposed criteria have to be flexible enough to be useful, “once they are validated — by both general health care providers without access to neuropsychological testing, advanced imaging, and CSF measures, as well as specialized investigators involved in research or clinical trial studies with access to these measures.”

By including criteria to help detect the disease earlier, it is hoped this will help identify the right people to take part in risk reduction and prevention research, said Phelps.

The workgroups will receive further input from the Alzheimer’s community via a website just launched by NIA and the Association.

The drafts will then be revised in the light of comments and feedback received, published in a peer-reviewed journal, and then validated through use in clinical trials.

Main source: Alzheimer’s Association.

Written by: Catharine Paddock, PhD