Plasma biomarkers combined with UPDRS and MoCA for differential assessments of amnestic cognitive impairment (aMCI), Parkinson’s disease (PD+PDD) and dementia with Lewy body (DLB): A pilot study

Abstract

AbstractBackgroundThere would be tremendous value for having biomarker panels as screening tools for the assessment of AD and PD pathologies. Technologies that increase the sensitivity and accuracy of the measurement of plasma Aβ42, total Tau (t‐Tau), phosphorylated Tau (P‐tau),) have emerged and there is interest in testing plasm alpha synuclein (α‐syn). The specific aim of the present study was to assess the accuracy of plasma Aβ42, total Tau (t‐Tau), and α‐syn combined with clinical measures in identifying mild cognitive impaired (MCI), PD/PDD, and DLB cases.MethodsThe total sample size was 77 subjects including 37 NC, 16 MCI [NIA‐AA Criteria, Alberts 2011], 12PD/PDD [Hughes criteria] and 12 DLB [McKeith criteria]. NC subjects reported no demonstrable cognitive complaints, were intact functionally and cognitively.. The variables included age, education, MOCA, UPDRS, and H‐Y stage. Plasma biomarkers were assayed by ImmunoMagnetic Reduction (IMR) technology (MagQu, Inc).ResultsMOCA scores were lower in the aMCI and DLB groups. The UPDRS and H‐Y stage scores were significantly higher in the PD and DLB groups. The sensitivities using biomarkers (abeta42xT‐Tau) or MoCA individually to discriminate aMCI from NC are 0.625 to 0.92, respectively. The combination of biomarker and MoCA shows the 0.929 for the sensitivity. As to the specificity, individual biomarker or MoCA shows 0.778, whereas the combination of biomarker and MoCA shows 0.833. .When clinical measures were combined with biomarker values (UPDRS w/alpha‐syn; DLB status could be differentiated from PD/PDD with a sensitivity 0.955, Specificity 0 980, The combination of p‐tau181 with UPDRS had a sensitivity of 0.833 and specificity of 0.833 which was better than the sensitivity and specificity of the individual measures.ConclusionsInvestigations on the discrimination of DLB vs. PDD are rare. In this pilot study, we show that IMR assays of plasma α‐Syn, P‐tau 181, and Aβ42 x t‐tau in combination with clinical measures (UPDRS and MOCA), could differentiate PD/PDD from DLB, as well as NC from aMCI. Thus, our data suggest clinical utility of these novel biomarker modalities and panels. Differentiating DLB from PDD could be consequential in clinical characterization. Future studies will aim to replicate our findings on larger group sizes.