An update to the diagnostic guidelines for Alzheimer’s Disease

Introduction to the recommendations from the National Institute on Aging and the Alzheimer's Association workgroup on diagnostic guidelines for Alzheimer's disease provides an update to the 1984 criteria for the clinical diagnosis of Alzheimer's Disease (AD), which were originally established by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA). To do so, the National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD, incorporating the scientific advances that have occurred since establishment of the original criteria. The recommendations were first presented at the ICAD meeting in 2010, revised through comments on the Alzheimer's Association web site, and then submitted to the NIA earlier this year. Although three work groups were devised, one focused on diagnostic criteria for the dementia phase of AD, one focused on the symptomatic pre-dementia phase known as MCI, and the other on the asymptomatic phase, a fourth workgroup focused on revising the pathological criteria for AD was recommended. The revisions made by this final workgroup will be submitted later this year. Notable differences are an incorporation of biomarkers of the underlying disease state, including both fluid and imaging measures, and formalization of different stages of disease in the diagnostic criteria, with a particular emphasis on the early stages of the disease. However, it is important to note that the use of biomarkers is limited to clinical research settings and that much additional work is needed to validate the application of biomarkers for diagnostic purposes. The core clinical criteria for AD dementia will continue to be the basis of the diagnosis in clinical practice. It is clear the guidelines provide more immediate importance in the research arena, but biomarker evidence is expected to enhance the pathophysiological specificity of an earlier diagnosis of AD dementia in the future.

Updates to the criteria for MCI were most notable for clinical purposes, with two sets of criteria developed:

1. Outlining the core clinical criteria for use by healthcare providers without access to advanced imaging or CSF measures
2. Describing research criteria that incorporate biomarkers for use in research and clinical trial settings

The final criteria for MCI due to AD has four requirements:

1. Concern regarding a change in cognition – noted by the patient, an informant, or a skilled clinician.
2. Impairment in at least one cognitive domain – most commonly in episodic memory.
3. A general preservation of independence in functional abilities.
4. Absence of dementia – changes should be mild enough to allow the individual to maintain their social and occupational roles.

A staging framework to assess for individuals at the greatest risk for developing clinical signs of impairment was also developed:

Stage 1 – asymptomatic cerebral amyloidosis

Stage 2 – amyloidosis and evidence of "downstream" neurodegeneration

Stage 3 – amyloidosis, evidence of neurodegeneration, and subtle cognitive and/or behavioral decline