Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.

Gemma Roberts,Louise Allan,Kirsty Olsen,Sean J Colloby,Calum A Hamilton,Tamir Ali,Nicola Barnett,Paul C Donaghy,John O'Brien,Sarah Lawley,Sally Barker,John-Paul Taylor,Joanna Ciafone,George Petrides,Kim Howe,Rory Durcan,Michael Firbank,Alan J Thomas,Jim Lloyd

doi:10.1192/bjp.2020.234

Abstract

Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3. It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

Highlights

Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer’s disease
Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically

Summary

Introduction

Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. The failure of new treatments in Alzheimer’s disease may be related to them being applied too late, and to people without pure Alzheimer’s disease pathology,[1] with Lewy body disease recognised as a common co-pathology even in well-characterised Alzheimer’s disease cohorts.[2] Biomarkers play a crucial role in accurate stratification and dopaminergic imaging is included as an indicative biomarker in the fourth dementia with Lewy bodies (DLB) consensus criteria, alongside cardiac sympathetic innervation imaging and polysomnography.[3] dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) is well-established as a diagnostic marker with good sensitivity and specificity in DLB, the recent Consensus research criteria for prodromal DLB at the mild cognitive impairment (MCI) stage (MCI-LB)[4] emphasise the need for prospective studies to assess the diagnostic accuracy of FP-CIT for MCI-LB

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Conclusion