Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment

Abstract

This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.

Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers

“…Three core CSF biomarkers (Aβ1-42, t-tau, and p-tau) reflect AD pathology and can be used to reliably diagnose AD and identify MCI, a prodromal stage of AD, with high diagnostic accuracy. [45,46] Previous studies showed that AD patients have a substantial reduction in CSF Aβ1-42 and a marked increase in levels of CSF t-tau and p-tau [47][48][49][50]. We observed that higher levels of TDCA:CA, GDCA:CA, and GLCA:CDCA were associated with decreased levels of CSF Aβ1-42 and higher levels of GCDCA, TLCA, and GLCA were associated with increased levels of CSF t-tau and p-tau.…”

Communicating mild cognitive impairment diagnoses with and without amyloid imaging

“…Amyloid imaging results strongly correlate with amyloid levels in CSF [44], and these recommendations may largely apply to disclosing results of that biomarker test. CSF, however, provides additional information that may facilitate adjustment of these recommendations [45]. Furthermore, the inclusion of other biomarkers such as regional glucose metabolism, brain volume, or information on tau pathology will increase the information for clinicians to use in assessing prognosis.…”

Blood-based biomarkers for Alzheimer’s disease—An update

“…Although CSF biomarkers have been made part of the clinical criteria for AD (Dubois et al, 2014) and standardized operating procedures for CSF sampling, processing and interpretation have been published (Herukka et al, 2017;Simonsen et al, 2017), the CSF sampling per se (through lumbar puncture) may be regarded as a barrier towards large scale clinical implementation; undoubtedly, a blood test would be easier.…”