Alongside a lack clinically validated, minimally invasive diagnostic tools for early diagnosis and/or monitoring of disease progression in Alzheimer’s Disease (AD), there are no sound metrological assessment protocols and measurements for cognition, nor measurement comparability through SI (System of International Units), traceability and uncertainty for regulatory approval of biomarkers. As part of the on-going EMPIR HLT04 NeuroMET project in which several national metrology institutes work together with clinicians and academics to overcome specific measurement issues to improve diagnosis and disease progression, we describe here the justification for and development of the ‘NeuroMET Memory Metric’ (version 0.1).
Re-examination of traditional widely used ‘legacy’ cognitive assessment protocols using invariant measurement theory aims at more accurately capturing the patient’s cognitive ability and improving the analysis of correlations with various AD biomarkers. Two principal elements provide sound metrological underpinnings: (i) a correct formulation of a measurement model; and (ii) proper handling of the ordinal cognitive data. In turn, this enables formulation of novel construct specification equations for patient cognitive ability as a function of diverse biomarkers (e.g., in plasma, CSF and saliva together with MRI/MRS data) as well as for cognitive task difficult as a function of test design.
To further improve the accuracy in patient’s cognitive ability work is now in progress to develop a NeuroMET Memory Metric based on legacy cognitive assessments (e.g., MMSE, Corsi Block Test, Digital Span Test). This work can be ascribed a level-5 construct theory. This means the realization of more fit-for-purpose, better targeted and better administered cognitive measurement systems. It will also enable traceable calibration of both additional cognitive tasks as well as the effects of intervention (or disease progression) on the cognitive ability of each individual patient.