Proposed Criteria Target Early Alzheimer's Diagnosis

PARIS, July 9 -- Episodic impaired memory rather than developing dementia is the crucial clinical symptom pointing to an Alzheimer's disease diagnosis, according to a proposal for revised diagnostic criteria.

The proposed criteria, a work in progress by an international consortium, are intended to permit earlier and "more specific Alzheimer's disease diagnosis" than the 24-year-old National Institute of Neurological and Communicative Diseases and Stroke (NINCDS) and the Alzheimer's disease and Related Disorders Association (ADRDA) criteria now in use.

The new criteria, which rely on a mix of imaging studies and biomarkers, combined with evidence of memory deficit, were published online today by Lancet Neurology.

Bruno Dubois, M.D., of INSERM and the Universit Pierre et Marie Curie, and an international working group, said the new criteria "move away from the traditional two-step approach of first identifying dementia according to the degree of functional disability, and then specifying its cause."

Instead the new criteria "aim to define the clinical, biochemical, structural, and metabolic presence of Alzheimer's disease."

However, Dr. Dubois and colleagues pointed out that their proposed criteria are limited by the lack of specifics such as definitions and parameters needed to implement them in clinical practice. As a result, "validation studies of the proposed diagnostic criteria will clearly be needed," they wrote.

The key or cornerstone criterion proposed by Dr. Dubois and colleagues is episodic memory deficit that is isolated or in combined with other cognitive changes. Other features of episodic memory deficit include:

• Gradual and progressive change in memory function reported by patients or informants over more than six months.
• Objective evidence of significantly impaired episodic memory on testing.

Memory deficit should be combined with one or more of these supportive features:

• Presence of medial temporal lobe atrophy including volume loss of hippocampi, entorhinal cortex, and amygdala as determined by MRI.
• Low amyloid 42 concentrations, increased total tau concentrations, or increased phospho-tau concentrations or combinations of these three.
• Reduced glucose metabolism in bilateral temporal parietal regions on functional PET, or other "well validated ligands, including those that foreseeably will emerge such as Pittsburgh compound B or FDDNP (fluoroethyl](methyl)amino]-2-naphthyl]ethylidene) malononitrile."
• Proven Alzheimer's disease autosomal dominant mutation within the immediate family.

Alzheimer's disease can be excluded as a diagnosis if there is a sudden onset of memory deficit or early occurrence of gait disturbances, seizures, or behavioral changes.

Other exclusion criteria are:

• Hemiparesis, sensory loss, visual field deficits.
• Major depression.
• Cerebrovascular disease.
• Toxic and/or metabolic abnormalities.
• MRI FLAIR or T2 signal abnormalities in the medial temporal lobe that are consistent with infectious or vascular insults.

In an essay that accompanied the new criteria proposal, Norman L. Foster, M.D., of the University of Utah in Salt Lake City, wrote that although "presented as criteria, the proposal from Dubois and colleagues should be thought of as a crucial framework for future discussion."

But Dr. Foster pointed out that as "currently constructed, the criteria would be impossible to implement, because they do not include an operational definition of methods and abnormal results."

He concluded that "these criteria are not ready for clinical use. Nevertheless, this new approach should quickly be Alzheimer's disease opted following standardization and validation."

Although "much work remains," Dr. Foster urged that "we seize this opportunity to reopen the discussion of Alzheimer's disease diagnosis."