Recently revised criteria for the clinical diagnosis of Alzheimer's disease (AD) focus on how the disease develops in addition to its clinical symptoms. The revised criteria identify three stages of the disease and incorporate biomarkers in the criteria for the first time.
The first revision since clinical diagnosis criteria were issued in 1984 reflects the vast expansion in understanding of the disease since then. The revised criteria were issued by three expert international workgroups convened in 2009 by the Alzheimer's Association and the National Institute on Aging (NIA) to review research findings in an effort to update diagnostic criteria based on current scientific knowledge and technology.
AD affects an estimated 5.2 million Americans and may strike as many as 13.5 million by 2050. AD is an irreversible form of dementia marked by memory loss, a progressive decline in intellectual ability, deteriorating language and speech skills, and personality and behavioral changes that eventually interfere with daily living. These symptoms result from decreased brain metabolism, loss of gray brain matter, cortical thinning, and brain atrophy. There is no laboratory test currently available that can positively diagnose the disease in living patients. AD can only be confirmed by microscopic examination of brain tissue after death. With advances in technology, a combination of imaging and laboratory tests may now help doctors make a reasonable clinical diagnosis of AD by enabling them to rule out other causes of dementia.
The 1984 criteria relied heavily on doctors’ clinical judgment based on symptoms reported by patients and family members in addition to the results of cognitive and neurological assessments. The update reflects new understanding that particular biomarkers — an indicator of the presence of a biochemical substance that may reflect evidence of disease — and imaging tests that may detect the onset and progression of disease can be useful in better understanding and diagnosing AD. The workgroups considered several AD biomarkers, focusing on the five most widely studied ones, divided into two categories: (1) biomarkers of ß-amyloid protein (Aß) accumulation, and (2) biomarkers of neuronal degeneration or injury.
- Evidence of abnormal Aß retention on PET imaging
- Decreased level of Aß42, a specific form of ß-amyloid protein, in cerebrospinal fluid (CSF)
- Elevated and abnormally altered tau protein, a structural protein of the brain that can create neurofibrillary tangles when changed chemically, in CSF
- Decreased uptake of fluorodeoxyglucose 18F (FDG), a sugar molecule, that can be identified via PET imaging
- Atrophy of brain structure, as shown by imaging tests
The criteria establish three phases of AD and stipulate biomarkers’ potential diagnostic role in each. In the newly named preclinical phase, when no physical or mental symptoms are yet seen, biomarkers that are currently used only in research subjects with no or subtle symptoms strongly support the presence of AD years before memory loss occur, and a research agenda is proposed. For the phase called mild cognitive impairment (MCI) that includes mild changes in memory and thinking ability, the criteria establish a framework for use of biomarkers to determine underlying cause of clinical deficit and disease progression. In the third phase, dementia due to AD, when dementia is evident and impairs a person’s ability to function, the workgroup established a research agenda for use of biomarkers to confirm AD as the cause of dementia.
The criteria call for more research on biomarkers that prove their diagnostic value and, more importantly, to standardize their use so that any clinical or research laboratory can get reliably reproducible results. The expanded criteria as established by the three workgroups have set a strategic pathway that going forward will result in improved early detection and management of AD.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Alzheimer's Association. New Diagnostic Criteria and Guidelines for Alzheimer's Disease. Available online at http://www.alz.org/research/diagnostic_criteria/ through http://www.alz.org. Accessed May 23, 2011.
Alzheimer's Association. Frequently Asked Questions: Publication of New Criteria and Guidelines for Alzheimer’s Disease Diagnosis. PDF available for download at http://www.alz.org/documents_custom/Alz_Diag_Criteria_FAQ.pdf through http://www.alz.org. Posted April 2011. Accessed May 23, 2011.
Clifford R. Jack Jr., et al. Introduction to the Recommendations from the National Institute on Aging and the Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease. Alzheimer’s & Dementia. PDF available for download at http://www.alz.org/documents_custom/Intro_Diagnostic_Recommendations_Alz_proof.pdf through http://www.alz.org. Issued April 16, 2011. Accessed May 23, 2011.