This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:
To determine the diagnostic accuracy of plasma and CSF amyloid biomarker levels for detecting Alzheimer's disease, and predicting progression to dementia, in patients with MCI.
Does the time between MCI diagnosis and plasma/CSF test matter? Yes, although it is unlikely that any intervention used to manage or treat MCI will impact on Aβ levels in plasma or CSF, it would be wrong to assume this. Therefore, studies should articulate the time between diagnosis of MCI and initial or baseline plasma and CSF sampling. Ideally this should be measured in days or weeks and not months.
How different are the criteria that define MCI? These different criteria may be more or less inclusive and therefore where greater degrees of cognitive impairment are necessary it has been shown that there are higher rates of conversion to Alzheimer's dementia Matthews 2008. Accordingly - the output from out review will be split by diagnostic entity as well as collectively for all definitions of MCI.
What is the difference in the assays we are accepting? Are the sensitivities/specificities similar? We don't know yet. We believe that different assays have different sensitivities and specificities though only those that satisfy certain quality criteria (selected by the laboratory based authors in our group) will be included for review.
Other potential sources of heterogeneity that will be extracted (where possible) will be methodology for applying diagnostic criteria for one of the dementia syndromes, duration of MCI prior to entering the cohort, age of sample, baseline cognitive tests scores, ApoE status, length of follow up and other factors which are identified in studies as they are collected which may influence the relationship between Aβ levels and conversion to Alzheimer's and other forms of dementia.