Is It Really, Really Alzheimer’s? New Guidelines for Diagnosis

Last year the National Institute on Aging and the Alzheimer's Association convened three working groups to update the diagnostic criteria for Alzheimer's disease, which was last done in 1984. The new guidelines have been published in the Journal Alzheimer's and Dementia. One of the main differences from the earlier guidelines is the attention given to biomarkers – tests that can be used to add confidence to clinical findings in both Alzheimer's disease and the earlier form, Mild Cognitive Impairment (MCI).

The diagnosis of Alzheimer's disease is still a clinical one, made by the physician with the help of an informant (members of the family, even the patient), by making a judgment call on the presence of dementia. The core clinical criteria for the diagnosis of Alzheimer's dementia are cognitive or behavioral symptoms that interfere with the ability to function at work or at usual activities, and are not explained by delirium or major psychiatric disease. Such changes may be determined by history-taking from the patient and/or informant, and an objective assessment, such as a mental status examination or neuropsychological testing. Cognitive or behavioral impairment involves at least two of the following: impaired memory (acquisition and retention), impaired reasoning and handling of complex tasks, poor judgment, impaired visuospatial abilities (and inability to recognize faces or common objects), impaired language functions, and changes in personality (uncharacteristic mode changes decreased interest, social withdrawal, loss of empathy, compulsive or obsessive behaviors, socially unacceptable behaviors).

Alzheimer's disease is usually classified as probable or possible. If there is uncertainty, consideration can be given to the use of biomarkers. Information on amyloid protein abnormalities can be obtained from a spinal tap or positive emission tomography (PET) scan. Evidence of neuronal degeneration can come from blood or spinal-fluid tau levels, decreased glucose uptake on PET, or cortical thinning on magnetic resonance imaging (MR I – see last week’s post).

The diagnosis of mild cognitive impairment (MCI) is also still mainly a matter of clinical judgment.  The use of biomarkers is recommended only in research settings, as not enough is known about them to make them reliable diagnostic tools - yet.  MCI is a progressive condition, and it can be difficult to mark its beginning or its transition to Alzheimer’s, which happens in many individuals. The core clinical criteria for diagnosis include:  concern regarding a change in cognition (obtained from the patient, an informant, or a skilled clinical observer), impairment in one or more cognitive domains (decision-making, language, attention, visuospatial skills, and episodic memory), but preservation of independence in daily functional abilities.  There should not be dementia.          

In summary, these two sets of guidelines confirm the importance of both Alzheimer’s and MCI diagnoses being based on clinical judgment, without the use of biomarker tests in most instances.  But the need for better biomarkers, or better information about existing biomarkers, is also made clear.  We hope that the next update will be sooner than 18 years away, and will have more definitive criteria to allow appropriate therapies (yet to be discovered) to be prescribed.