New guidelines for Alzheimer’s diagnosis

By Heather Camlot

The two step-approach currently used to diagnosis Alzheimer’s disease is outdated, says a consortium of experts in the August issue of The Lancet Neurology.

Dr. Bruno Dubois, a leading Alzheimer’s expert from Hôpital de la Salpêtrière in Paris, and his colleagues propose a new formula in which patients must first exhibit progressive memory loss over a six-month period as well as at least one of the following physical “biomarkers” of the disease:

  • Atrophy in a particular part of the brain, as shown by MRI
  • Abnormal proteins in the cerebrospinal fluid
  • Brain activity linked to Alzheimer’s, as shown by PET scan
  • A genetic mutation for Alzheimer’s.

“These new criteria are centred on a clinical core of early and significant episodic memory impairment,” write the authors in their position paper. “The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis.”

“If an earlier diagnosis can be achieved, then treatments could be initiated earlier, and as in all medical conditions, the earlier the treatment the better the outcome,”  says Dr. Jack Diamond, scientific director of the Alzheimer Society of Canada.

Currently, doctors can only offer a possible or probable diagnosis by looking at memory loss, impairment of other mental functions and how these relate to daily activities. These criteria were breakthroughs in 1984, when they were published by the National Institute of Neurological Disorders and Stroke-Alzheimer Disease and Related Disorders (NINCDS-ADRDA) working group. The experts, however, propose moving away from the two-step approach of identifying dementia and then specifying its cause, preferring to “define the clinical, biochemical, structural, and metabolic presence of AD.”

One major problem remains: the expensive, high-tech tests mentioned above have yet to be validated — meaning able to prove detection within specific limits. In their paper, Dubois and colleagues call for research to be conducted to this end.

THE MRI and PET approaches are already well established, explains Dr. Diamond, but its use needs to be increased and followed clinically for a larger sample size that would satisfy statistical and epidemiological standards. “The identification of abnormal proteins or protein levels in the CSF (the cerebrospinal fluid that bathes the brain and spinal cord) needs more studies in this regard,” says Dr. Diamond, “though when these are completed, this test promises well in both ease of the procedure and accuracy of the chemical assay involved.” Finally, genetic testing is useful as supporting data, he explains, but can only be used diagnostically for the genes involved in Familial form of Alzheimer’s disease (FAD), which accounts for five to seven percent of all cases of AD.

Alzheimer’s is a progressive, degenerative disease that appears to occur when a number of factors, including age, genetics, lifestyle and environment, overwhelm the brain’s self-repair and self-healing mechanisms. According to the Alzheimer Society of Canada, some 300,000 Canadians over the age of 65 (two-thirds of which are women) have been struck by the disease and another 150,000 have a related disease, such as vascular dementia and Creutzfeldt-Jakob disease. More than 24 million people around the world have Alzheimer’s or a related disease — and that number is projected to increase to 81 million by the year 2040.

Although Alzheimer’s is fatal, Dr. Diamond says the risk of onset can be reduced. “In general, by adopting healthy lifestyles, by exercising both brain and body, by eating as much as possible foods corresponding to the “Mediterranean diet”  and importantly, by dealing aggressively with the conditions mentioned as constituting risk factors for Alzheimer’s disease.”

Meanwhile, several promising drugs are in clinical trials, and medications to treat some of the symptoms are already on market. The U.S. Food and Drug Administration last month approved the first skin patch for treating mild to moderate cases of the disease. The drug in the patch, Exelon, or rivastigmine, is already available in oral and capsule form in the U.S. and Canada; the patch, however, causes fewer problems with nausea and vomiting, provides a continuous dose of the drug and eliminates having to remember to take pills. The prescription patch will be available in the U.S. soon and is currently under review by Health Canada.

First appeared on in August 2007.