In vivo detection of Alzheimer's and Lewy body disease concurrence: Clinical implications and future perspectives

Abstract

AbstractINTRODUCTIONThe recent introduction of seed amplification assays (SAAs) detecting misfolded α‐synuclein, a pathology‐specific marker for Lewy body disease (LBD), has allowed the in vivo identification and phenotypic characterization of patients with co‐occurring Alzheimer's disease (AD) and LBD since the early clinical or even preclinical stage.METHODSWe reviewed studies with an in vivo biomarker‐based diagnosis of AD‐LBD copathology.RESULTSStudies in large cohorts of cognitively impaired individuals have shown that cerebrospinal fluid (CSF) biomarkers detect the coexistence of AD and LB pathology in approximately 20%–25% of them, independently of the primary clinical diagnosis. Compared to those with pure AD, AD‐LBD patients showed worse global cognition, especially in attentive/executive and visuospatial functions, and worse motor functions. In cognitively unimpaired individuals, concurrent AD‐LBD pathologies predicted longitudinal cognitive progression with faster worsening of global cognition, memory, and attentive/executive functions.DISCUSSIONFuture research studies aiming for a better precision medicine approach should develop SAAs further to reach a quantitative evaluation or staging of each underlying pathology using a single biofluid sample.Highlights α‐Synuclein seed amplification assays (SAAs) provide a specific marker for Lewy body disease (LBD). SAAs allow for the in vivo identification of co‐occurring LBD in patients with Alzheimer's disease (AD). AD‐LBD coexist in 20‐25% of cognitively impaired elderly individuals, and ∼8% of those asymptomatic. Compared to pure AD, AD‐LBD causes a faster worsening of cognitive functions. AD‐LBD is associated with worse attentive/executive, memory, visuospatial and motor functions.