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Thursday, June 26, 2014

New Criteria for Diagnosing and Defining Alzheimer’s

by Jamie Talan


With a more in-depth understanding of the clinical and pathophysiological features of Alzheimer’s disease (AD), a team of international investigators — the International

Working Group (IWG) — has refined research diagnostic criteria that they first proposed in 2007.

The latest IWG revisions, which were published in the June issue of Lancet Neurology, rely on specific biomarkers to make a definitive diagnosis, but are intended for research purposes only. There are almost 60 different clinical studies underway and such diagnostic information is crucial to identify patients with AD, especially in its earliest forms. Recent studies have shown that 20 to 30 percent of AD patients in the pre-biomarker era were later tested and amyloid is only one component of clinical dementia and does not have to be present.

Bruno Dubois, MD, director of the l’Institut de la Mémoire et de la Maladie d’Alzheimer at the Hôpital Pitié Salpêtrière in Paris, who led the IWG guideline effort, said that he never felt comfortable with the low accuracy for the diagnosis for AD. In the mid-2000s, Dr. Dubois gathered a team of AD experts to begin thinking about a new definition of AD. During most of his tenure as a neurologist, the diagnosis was purely a clinical one.

“I never saw why Alzheimer’s should be the only disease where it must reach a threshold of severity for people to receive a diagnosis,” said Dr. Dubois. “Normally, we try to diagnose diseases when they start. The argument was that no one really needed to make a diagnosis for a disease for which there were no treatments. That just wasn’t a good argument. I never understood why we should wait for dementia. Many things can cause dementia. It is better to characterize what is behind the syndrome.”

So he set out to improve the accuracy of the diagnosis and allow researchers to arrive at a diagnosis early in the course of the disease. The pathophysiological biomarkers developed in the last decade fit nicely into his vision.

Dr. Dubois said the IWG proposed a simplified algorithm that encompasses AD at any stage of the disease. The evidence continues to support the presence of an amnestic syndrome of the hippocampal type as the clinical core criterion for typical AD, he said, which could best be identified with a list-learning memory test such as the free and cued selective reminding test as well as other delayed recall tests.

Along with behavioral and cognitive changes, the IWG criteria depend on evidence of a positive biomarker in CSF — low amyloid beta 42 and high tau or high phosphorylated tau. The committee felt that MRI biomarkers to identify hippocampal atrophy or findings on FDG PET are not necessary to make a diagnosis; but that these were more downstream effects.

The IWG also included diagnostic information for other atypical forms of AD, including posterior cortical atrophy, logopenic aphasia variant, and frontal variant. The biomarkers needed to confirm a diagnosis include CSF (low amyloid beta 42 and high tau or high phosphorylated tau) or a positive amyloid PET scan.

See a full discussion of these updated criteria in the July 3 issue of Neurology Today. For our previous coverage of Alzheimer’s disease criteria and diagnosis, see