A Longitudinal Study of Plasma pTau181 in Mild Cognitive Impairment with Lewy Bodies and Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) co-pathology is common in dementia with Lewy bodies and is associated with increased decline. Plasma pTau181 is a blood-based biomarker that can detect AD co-pathology.

Objectives: We investigated whether pTau181 was associated with cognitive decline in mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with AD (MCI-AD).

Methods: We assessed plasma pTau181 using a single-molecule array (Simoa) immunoassay at baseline and follow-up in a longitudinal cohort of MCI-LB, MCI-AD, and controls.

Results: One hundred forty-six subjects (56 probable MCI-LB, 22 possible MCI-LB, 44 MCI-AD, and 24 controls) were reviewed for up to 5.7 years. Probable MCI-LB had significantly higher pTau181 (22.2% mean increase) compared with controls and significantly lower (24.4% mean decrease) levels compared with MCI-AD. Receiver operating characteristic analyses of pTau181 in discriminating probable MCI-LB from controls showed an area under the curve (AUC) of 0.68 (83% specificity, 57% sensitivity); for discriminating MCI-AD from healthy controls, AUC was 0.8 (83.3% specificity, 72.7% sensitivity). pTau181 concentration was less useful in discriminating between probable MCI-LB and MCI-AD: AUC of 0.64 (71.4% specificity, 52.3% sensitivity). There was an association between pTau181 and cognitive decline in MCI-AD but not in MCI-LB. In a subset with repeat samples there was a nonsignificant 3% increase per follow-up year in plasma pTau181. The rate of change in pTau181 was not significantly different in different diagnostic subgroups.

Conclusions: pTau181 was not associated with an increased decline assessed using either baseline or repeat pTau181. pTau181 partially discriminated probable MCI-LB from controls and MCI-AD from controls but was not useful in distinguishing probable MCI-LB from MCI-AD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: biomarkers; dementia with Lewy bodies; mild cognitive impairment; pTau181; plasma.

FIG 1

(A) Raw plasma pTau181 measurements in each diagnostic group at baseline; (B) ROC (receiver operating characteristic) curves for the differentiation of MCI‐AD and MCI‐LB from healthy controls. AD, Alzheimer's disease; LB, Lewy bodies; MCI, mild cognitive impairment. [Color figure can be viewed at wileyonlinelibrary.com]

FIG 2

Latent trajectories of cognitive function, centered on the last observation: (A) with adjusted estimated trajectories for each class and (B) raw pTau181 concentrations for each diagnostic group, stratified by latent trajectory; dashed line indicates a cutoff of 1.929 pg/mL pTau181. [Color figure can be viewed at wileyonlinelibrary.com]