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. Author manuscript; available in PMC: 2012 Dec 1.
Published in final edited form as: Neurobiol Aging. 2011 Dec;32(Suppl 1):S4–S9. doi: 10.1016/j.neurobiolaging.2011.09.003

Table.

Levels of Evidence for AD Biomarkers

Marker type Diagnosis of AD versus controls Diagnosis of MCI versus controls Prognosis: predicting progression from MCI to AD Prognosis: predicting progression from cognitively normal to MCI or AD
CSF biomarkers Primary studies - Sufficient evidence of a direct relationship1* Primary studies - Sufficient evidence of a direct relationship1** Primary studies - Sufficient evidence of a direct relationship1*** Primary studies - Sufficient evidence of a direct relationship1

Levels of evidence are based on Categories of Association established and used by the Institute of Medicine for association between a biomarker and a specific health outcome (Committee on Health Effects Associated with Exposures During the Gulf War. Institute of Medicine, 2000): 1. Sufficient Evidence of a Direct Relationship: Evidence fulfills the guidelines for sufficient evidence of an association, is supported by experimental data in humans and animals, and satisfies several of the guidelines used to assess causality: strength of association, dose–response relationship, consistency of association, and a temporal relationship. 2. Sufficient Evidence of an Association: Evidence of association is sufficient to conclude that there is a positive consistent association, in human studies in which chance and bias, including confounding, could be excluded with reasonable confidence. It differs from category 1 because of the lack of experimental data in humans or animals that support the relationship. 3. Limited/Suggestive Evidence of an Association: Evidence is suggestive of an association between a biomarker and a specific health outcome in human studies, but the body of evidence is limited by the inability to exclude chance and bias, including confounding, with confidence. 4. Inadequate/Insufficient Evidence to Determine Whether an Association Exists: Evidence is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between exposure to a specific agent and a specific health outcome in humans.

*

There are over 50 studies (including cross-sectional and longitudinal studies) for CSF tau, over 16 studies including longitudinal studies for CSF Aβ42, and over 5 studies including longitudinal studies for the combination of tau and Aβ42.

**

Several studies indicate that CSF biomarkers can detect very mild dementia (MCI) with a sensitivity that is similar to that of more advanced AD.

***

There are several studies including studies with neuropathological confirmation of diagnoses.

Evidence is limited to a small number of studies with methodological variations.