MADRID – A set of newly proposed criteria could bring the diagnosis of Alzheimer's disease into the 21st century by shifting the focus from one based on loss of function toward one that incorporates measurable disease-induced biochemical and structural changes.
For a diagnosis of Alzheimer's disease (AD), the proposed criteria would require presence of an objective confirmed episodic memory disorder plus at least one of the following: a structural abnormality, probably atrophy of the mediotemporal lobe as seen on magnetic resonance imaging; a characteristic biochemical marker obtained from cerebrospinal fluid (CSF); or functional brain impairment as seen on positron emission tomography or single photon emission computed tomography.
The criteria were proposed by the International Working Group on Diagnostic Criteria for Mild Cognitive Impairment/Alzheimer's Disease and were unveiled at the 10th International Conference for Alzheimer's Disease and Related Disorders.
Implementation will require years of testing across all stages of the disease. But the proposed criteria eventually could be a reliable way of distinguishing patients with AD from those with mild cognitive impairment (MCI) and other memory disorders, said Dr. Howard Feldman of the University of British Columbia's Clinic for Alzheimer's Disease and Related Disorders, Vancouver.
“We now diagnose dementia largely based on functional impairments,” Dr. Feldman said. “One of the flaws with this is that it's not clear that function has a real neurobiological correlate, and it's difficult to put everyone on the same plane functionally.”
However, recent advances regarding the clinical, structural, pathologic, and biochemical hallmarks of dementia can serve as the basis for a much more targeted diagnostic method, he said. “It's time to package these into a new set of criteria that work in mild, moderate, and advanced stages of the disease as well as in the prodromal stage.” The cornerstone of the proposed criteria is the requirement for an episodic memory disorder, which must be gradual, progressive, and of at least 6 months' duration.
Tests of delayed recall are the best at distinguishing cognitively normal patients from those with MCI who will progress to AD, Dr. Feldman said. “It's imperative that we have a test that will allow for controlled encoding, a very important dimension of the impaired episodic memory in Alzheimer's.” These types of tests, including the delayed recall and double memory tests, differentiate between the memory storage or encoding problems, which are characteristic of AD, and problems involving memory retrieval.
The medial temporal structural assessment could either be done qualitatively, on the hippocampus, choroidal fissure, or temporal horn, or quantitatively on hippocampus, entorhinal cortex, or parahippocampal gyrus. “Studies suggest good sensitivity and specificity for AD and normal patients, and good discrimination of those who will progress from MCI.”
The proposed biochemical criterion would involve CSF measures of amyloid β1–42, total tau, or phospho tau. Finally, the functional brain scanning criterion on PET would show diminished glucose metabolism in the bilateral temporoparietal regions and posterior cingulate.
More research will be necessary to further hone each criterion, Dr. Feldman said. “We need to deal with the extent of abnormality each one would measure, and find cutoff points and specific instruments for each.”
Funding for Imaging Studies in Dementia
The Alzheimer's Disease Neuroimaging Initiative–a 5-year study looking at imaging technology to improve early diagnosis and gauge the effectiveness of treatments–got a $2.1 million boost last month from the Alzheimer's Association.
Officials at the association had previously granted $1 million to help fund this $60 million public-private initiative launched by the National Institute on Aging in 2004.
The project is aimed at testing whether serial magnetic resonance imaging, positron emission tomography, biologic markers, and clinical and neuropsychological assessments can be used together to measure the progression of mild Alzheimer's disease and mild cognitive impairment.
Researchers also will evaluate the use of PET scans with Pittsburgh Compound B (PIB). “PET/PIB technology will be a valuable addition to the study,” Dr. Samuel Gandy, chair of the Alzheimer's Association's Medical and Scientific Advisory Council, said in a statement. Patients are currently being recruited for the study. For more information, check
www.nia.nih.gov/Alzheimers/ResearchInformation/ClinicalTrials/ADNI.htm